Structure and Function of the Blood Brain Barrier

Dr Oliver Finlay

KEY POINTS

1. The blood-brain barrier (BBB) separates the brain from the blood and regulates the movement of molecules into and out of the brain.

2. The BBB is composed of endothelial cells, pericytes, and astrocytes, and has several functions, including protecting the brain from toxins and regulating the exchange of nutrients and waste products.

3. The BBB undergoes changes with age and in different diseases, leading to increased risk of brain damage and cognitive decline.

4. The BBB plays a critical role in regulating the nutrition of the brain, and changes in its permeability and function can affect the nutrition of the brain, leading to cognitive decline and neurodegenerative diseases.

5. Maintaining the structure and function of the BBB is important, and strategies like exercise, diet, managing chronic conditions, and limiting alcohol and drug use can help protect the BBB.

The brain is an essential organ responsible for cognitive, behavioural, and motor functions. It needs a constant supply of nutrients and oxygen to maintain its proper function. The blood-brain barrier (BBB) is a specialized system that separates the brain from the blood and ensures that only the essential components reach the brain. The BBB is a complex structure formed by specialized cells, including endothelial cells, pericytes, and astrocytes, which work together to regulate the movement of molecules into and out of the brain. This paper will discuss the structure and function of the BBB, the changes it undergoes with age and in different diseases, and how it affects the nutrition of the brain.

Structure and Function of the Blood-Brain Barrier

The BBB is composed of three main components: endothelial cells, pericytes, and astrocytes. Endothelial cells form the inner lining of blood vessels in the brain and are connected by tight junctions, which form a physical barrier that prevents the entry of most molecules from the blood into the brain. Pericytes are small cells that wrap around the endothelial cells and play a critical role in maintaining the BBB's integrity. Astrocytes are star-shaped cells that surround the blood vessels and regulate the exchange of nutrients and waste products between the blood and the brain.

The BBB has several functions, including protecting the brain from toxins, regulating the exchange of nutrients and waste products, and maintaining a stable environment for the brain. The BBB selectively allows the entry of essential molecules, such as glucose, amino acids, and some vitamins, into the brain while preventing the entry of harmful molecules, such as toxins and pathogens. The BBB also removes waste products from the brain, such as carbon dioxide and lactic acid, and maintains a stable environment by regulating the levels of ions and other molecules in the brain.

Structural Changes Through Aging

The BBB undergoes several changes with age, including changes in its morphology and function. Changes in the blood-brain barrier have also been observed in neurodegenerative diseases such as Alzheimer's and Parkinson's, as well as in systemic inflammation. These changes can lead to an increased risk of brain damage and cognitive decline. Studies have shown that the BBB becomes more permeable with age, allowing harmful molecules to enter the brain, leading to inflammation and damage. The expression of tight junction proteins also decreases with age, leading to a breakdown of the BBB's physical barrier.

Structural Changes in Pathology

Several diseases can affect the BBB, including neurodegenerative diseases, traumatic brain injury, and brain tumours. In neurodegenerative diseases such as Alzheimer's and Parkinson's, the BBB becomes more permeable, allowing the entry of harmful molecules into the brain, leading to inflammation and damage. Traumatic brain injury can also cause damage to the BBB, leading to increased permeability and the entry of harmful molecules into the brain. Brain tumours can disrupt the BBB's physical barrier, leading to the entry of molecules that can promote tumour growth.

Structural Changes in Systemic Inflammation

Systemic inflammation can affect the BBB, leading to increased permeability and the entry of harmful molecules into the brain, thus compromising its protective function. Studies have shown that inflammation can disrupt the tight junctions between endothelial cells, leading to increased permeability. Such changes have been shown to occur in neurodegenerative disease states such as Alzheimer’s and Parkinson’s disease.

How the Blood Brain Barrier Regulates Nutrition for the Brain

The BBB plays a critical role in regulating the nutrition of the brain. It regulates the transport of nutrients from the blood to the brain, including glucose, amino acids, and lipids. This process is essential for the brain to function correctly and for the maintenance of brain health. It selectively allows the entry of essential nutrients, such as glucose and amino acids, while preventing the entry of harmful molecules. Changes in the BBB's permeability and function can affect the nutrition of the brain, leading to cognitive decline and the development of neurodegenerative diseases. Studies have shown that BBB dysfunction can lead to a decrease in glucose uptake in the brain, leading to energy deficits that can contribute to the development of Alzheimer's disease.

Because of the importance of the blood-brain barrier in protecting the brain and regulating nutrient transport, it is essential that medication and supplements be tailored to address its structure. If the drug is too large or hydrophilic, it will not cross the BBB, limiting its effectiveness. Researchers are developing new methods to improve drug delivery to the brain, such as nanoparticles that can cross the BBB and to target specific areas of the brain for treatment of neurological diseases.

Strategies to Maintain the Structure and Function of the Blood Brain Barrier Through Ageing

There are several things we can do to help maintain the structure and function of the BBB as we age. Here are a few:

1. Exercise: Regular exercise has been shown to improve BBB function by increasing blood flow to the brain and reducing inflammation.

2. Diet: Eating a healthy diet rich in fruits, vegetables, whole grains, and lean proteins can help protect the BBB. Studies have found that certain nutrients, such as omega-3 fatty acids and antioxidants, can help reduce inflammation and oxidative stress in the brain, which can help maintain BBB integrity.

3. Manage chronic conditions: Chronic conditions like hypertension and diabetes can damage the BBB over time. Managing these conditions through lifestyle changes and medication, if needed, can help protect the BBB.

4. Limit alcohol and drug use: Excessive alcohol and drug use can damage the BBB and increase its permeability, leading to increased risk of cognitive decline and neurological disorders.

By following these steps, we can help maintain the structure and function of the BBB as we age, which can help protect our brain health.

Summary

In conclusion, the blood-brain barrier is a crucial structure that plays a vital role in the healthy function of the brain. Changes in the structure and function of the blood-brain barrier can have significant effects on brain health, including cognitive decline and an increased risk of neurodegenerative diseases. The development of new therapies that can target the blood-brain barrier and improve its function could have important implications for the treatment of neurological diseases in the future.

REFERENCES & EVALUATION OF SCIENTIFIC POWER

Abbott, N.J., 2013. Blood–brain barrier structure and function and the challenges for CNS drug delivery. Journal of Inherited Metabolic Disease, 36, pp.437-449.

OVERVIEW: The blood-brain barrier (BBB) is a structure that protects the brain from harmful substances in the bloodstream while allowing necessary nutrients to pass through. This article focuses on the structure and function of the BBB and the challenges of delivering drugs to the central nervous system (CNS). The author discusses the importance of understanding the BBB in drug development for CNS diseases such as Alzheimer's and Parkinson's.

STRENGTHS: Abbott's article provides a comprehensive overview of the BBB and its role in CNS drug delivery. The author covers the anatomical and physiological features of the BBB, as well as the transport mechanisms that allow certain molecules to pass through. The article also discusses various techniques for drug delivery to the CNS, including drug modification and the use of carrier systems.

LIMITATIONS: One limitation of the article is that it primarily focuses on the challenges of drug delivery to the CNS, rather than providing solutions to these challenges. The author briefly mentions several techniques for drug delivery but does not go into great detail about the efficacy or feasibility of these methods.

SCIENTIFIC POWER: MODERATE to STRONG - The author provides a thorough overview of the BBB and its functions and references a significant amount of research to support their claims. However, as previously mentioned, the article could benefit from more in-depth analysis of drug delivery techniques and their limitations.

Overall, Abbott's article provides a valuable overview of the BBB and its role in CNS drug delivery. The article serves as a useful introduction to the topic but could be complemented by further research on drug delivery methods and their effectiveness.

Abbott, N.J. and Friedman, A., 2012. Overview and introduction: the blood–brain barrier in health and disease. Epilepsia, 53, pp.1-6.

OVERVIEW: In this article, Abbott and Friedman provide an overview of the BBB, its structure and function, and its role in health and disease.

STRENGTHS: The article provides a comprehensive overview of the BBB and its function in protecting the brain from harmful substances. It also covers the challenges of drug delivery to the brain and the potential solutions that have been proposed.

LIMITATIONS: The article mainly provides a general overview of the BBB and does not go into much detail about specific diseases or conditions that are affected by the BBB. It also does not provide any new experimental data, as it is a review article that synthesizes information from previous studies.

SCIENTIFIC POWER: MODERATE to STRONG - It is based on a thorough review of the existing literature on the BBB and provides a good introduction to the topic for those new to the field. However, as it is not based on any original research, it may not be as informative for researchers who are already familiar with the subject. Overall, it is a useful resource for those interested in learning about the BBB and its role in health and disease.

Abbott, N.J., Patabendige, A.A., Dolman, D.E., Yusof, S.R. and Begley, D.J., 2010. Structure and function of the blood–brain barrier. Neurobiology of Disease, 37(1), pp.13-25.

OVERVIEW: This article provides an in-depth explanation of the structure and function of the blood-brain barrier.

STRENGTHS: The article provides a detailed overview of the various components that make up the blood-brain barrier, including the cells and proteins involved in its formation and maintenance. It also discusses the different mechanisms by which molecules can cross the barrier, such as passive diffusion and active transport. Additionally, the article highlights the important role of the blood-brain barrier in protecting the brain from various diseases and injuries.

LIMITATIONS: One potential limitation of the article is that it primarily focuses on the structure and function of the blood-brain barrier in healthy individuals. While it briefly mentions some diseases that can affect the barrier, it does not provide a comprehensive overview of how these diseases impact its function.

SCIENTIFIC POWER: MODERATE to STRONG - It is well-written and provides a detailed overview of the blood-brain barrier, drawing on a range of scientific studies to support its claims. However, as mentioned above, it could benefit from a more in-depth discussion of the impact of various diseases on the barrier's function.

Alahmari, A., 2021. Blood-brain barrier overview: structural and functional correlation. Neural Plasticity, 2021.

OVERVIEW: In the article the author explains the structure and function of the BBB and how it helps protect the brain. The article also discusses some of the challenges in developing drugs to treat brain diseases due to the BBB.

STRENGTHS: The article provides a comprehensive overview of the BBB, including its structure, function, and role in protecting the brain. The author uses simple language and clear explanations, making it easy for readers to understand. The article also references several studies that provide evidence for the information presented.

LIMITATIONS: One limitation of the article is that it does not delve deeply into the mechanisms of BBB function, or the methods used to study it. Additionally, the article does not discuss any recent advances in BBB research, which may be important for students and researchers interested in this topic.

SCIENTIFIC POWER: MODERATE to STRONG - While it does not present any ground-breaking research, it does provide a clear and concise overview of the BBB and its importance in protecting the brain. The author references several studies to support their claims, making the article a reliable source of information on this topic.

Ballabh, P., Braun, A. and Nedergaard, M., 2004. The blood–brain barrier: an OVERVIEW: structure, regulation, and clinical implications. Neurobiology of Disease, 16(1), pp.1-13.

OVERVIEW: This article provides an overview of the structure and function of the BBB, as well as its regulation and clinical implications.

STRENGTHS: The article provides a thorough overview of the BBB, covering its structure and function, as well as its regulation and clinical implications. The authors provide a detailed analysis of the different cell types that make up the BBB and their role in regulating the passage of molecules into and out of the brain.

LIMITATIONS: The article focuses primarily on the role of the BBB in neurological diseases and may not provide as much information on the role of the BBB in other areas of medicine.

SCIENTIFIC POWER: STRONG - The authors are highly regarded experts in the field, and their work has been widely cited by other researchers. The article is published in a reputable scientific journal and has undergone a rigorous peer-review process.

Overall, this article provides a valuable introduction to the structure and function of the BBB, as well as its regulation and clinical implications. While some of the information may be outdated, it is still a valuable resource for anyone interested in learning more about this important protective barrier.

Banks, W.A., Reed, M.J., Logsdon, A.F., Rhea, E.M. and Erickson, M.A., 2021. Healthy aging and the blood–brain barrier. Nature Aging, 1(3), pp.243-254.

OVERVIEW: This article by Banks et al explores the changes in the BBB that occur with aging and their implications for brain health.

STRENGTHS: The article provides a comprehensive overview of the current understanding of the BBB and its role in aging. It includes a thorough analysis of the mechanisms underlying BBB dysfunction and the potential consequences for brain health. The authors also discuss current research efforts aimed at improving our understanding of the BBB and developing interventions to protect it.

LIMITATIONS: While the article is informative, it focuses primarily on animal models and there is a need for more human studies. Additionally, the authors do not provide concrete recommendations for individuals to maintain the health of their BBB.

SCIENTIFIC POWER: MODERATE to STRONG - The authors provide a thorough review of the literature on BBB function and aging, and draw on a variety of sources to support their arguments. However, as noted above, the lack of human studies and concrete recommendations limits the scientific power of the article. Nonetheless, the article is an important contribution to the field of aging and brain health.

Begley, D.J. and Brightman, M.W., 2003. Structural and functional aspects of the blood-brain barrier. Peptide Transport and Delivery into the Central Nervous System, pp.39-78.

OVERVIEW: In this article, Begley and Brightman provide a comprehensive review of the structural and functional aspects of the BBB, particularly the transport of peptides into the central nervous system. The authors discuss the mechanisms that control the passage of molecules across the BBB and the challenges involved in drug delivery to the brain.

STRENGTHS: This article provides a detailed overview of the structural and functional aspects of the BBB, with a focus on peptide transport. The authors discuss various aspects of BBB, including its anatomy, physiology, and mechanisms of transport. The article also covers the latest research on drug delivery to the brain and the challenges faced by researchers.

LIMITATIONS: The article is quite technical, and some of the concepts may be challenging for readers without a strong background in neuroscience. Additionally, the article was published in 2003, and some of the information presented may be outdated.

SCIENTIFIC POWER: MODERATE to STRONG - The authors are experts in the field of BBB research and provide a comprehensive review of the subject matter. However, given that the article was published nearly two decades ago, some of the information presented may not be up to date.

Benz, F. and Liebner, S., 2020. Structure and function of the blood–brain barrier (BBB). In Physiology, Pharmacology and Pathology of the Blood-Brain Barrier (pp. 3-31). Cham: Springer International Publishing.

OVERVIEW: This article provides an overview of the structure and function of the BBB, including the different cell types involved, the transport mechanisms used, and how it is regulated.

STRENGTHS: This article provides a comprehensive overview of the BBB, covering a wide range of topics, including the structure, function, and regulation of the barrier. It is written in a clear and concise manner, making it accessible to a wide range of readers. Additionally, the authors use illustrations and diagrams to help explain the complex concepts, making it easier to understand.

LIMITATIONS: One potential limitation of this article is that it is primarily focused on the structural and functional aspects of the BBB and does not delve into the clinical implications of BBB dysfunction. Furthermore, the article does not provide an in-depth analysis of some of the more recent advances in BBB research, which may limit its usefulness for researchers looking to stay up to date on the latest findings.

SCIENTIFIC POWER: MODERATE to STRONG - While it provides a comprehensive overview of the BBB, it does not provide any new ground-breaking discoveries. However, the authors' expertise and the extensive research they have synthesised make this article an excellent resource for those looking to gain a thorough understanding of the BBB's structure and function.

Bernacki, J., Dobrowolska, A., Nierwiñska, K. and Malecki, A., 2008. Physiology and pharmacological role of the blood-brain barrier. Pharmacol rep, 60(5), pp.600-622.

OVERVIEW: This article provides a comprehensive review of the physiology and pharmacological role of the BBB. The authors discuss in detail the structure and function of the BBB, including the various transport mechanisms that regulate the movement of substances across the barrier.

STRENGTHS: The article also describes the role of the BBB in protecting the brain from harmful substances and the importance of maintaining BBB integrity for proper brain function.

LIMITATIONS: The article primarily focuses on the physiology and pharmacological role of the BBB and does not provide an in-depth discussion of the clinical implications of BBB dysfunction. It may also be challenging for readers without a background in pharmacology to understand some of the technical terms used in the article.

SCIENTIFIC POWER: MODERATE to STRONG - The authors provide a comprehensive overview of the BBB, and the information presented is supported by a range of scientific studies. However, the article was published in 2008, and newer research may have since been conducted on the topic.

Betsholtz, C., 2014. Double function at the blood–brain barrier. Nature, 509(7501), pp.432-433.

OVERVIEW: This article focuses on the dual function of the BBB, not only as a barrier, but also as a gatekeeper.

STRENGTHS: It highlights recent research that has shown how the BBB can selectively transport certain substances into the brain, such as glucose and essential amino acids. The article also discusses the potential therapeutic applications of targeting the BBB, for example, to deliver drugs directly to the brain to treat neurological disorders.

LIMITATIONS: This article is a brief commentary and does not provide an in-depth analysis of the structure and function of the BBB. It does not provide empirical evidence or experiments to support its claims.

SCIENTIFIC POWER: MODERATE - This article presents a brief overview of recent research on the BBB, but its scientific power is limited because it is not a comprehensive review or original research article. Nonetheless, it is a useful starting point for those interested in learning more about the BBB's dual function and potential therapeutic applications.

Bors, L., Tóth, K., Tóth, E.Z., Bajza, Á., Csorba, A., Szigeti, K., Máthé, D., Perlaki, G., Orsi, G., Tóth, G.K. and Erdő, F., 2018. Age-dependent changes at the blood-brain barrier. A Comparative structural and functional study in young adult and middle aged rats. Brain Research Bulletin, 139, pp.269-277.

OVERVIEW: In this study, researchers compared the structural and functional changes of the BBB between young adult and middle-aged rats.

STRENGTHS: This study used a comparative approach, which allowed researchers to directly compare the BBB changes between the two age groups. The study also utilised various techniques, such as electron microscopy and in vivo imaging, to examine both the structural and functional changes of the BBB. This comprehensive approach provides a more complete understanding of the age-dependent changes in the BBB.

LIMITATIONS: This study only examined two age groups (young adult and middle-aged), so it is unclear how the BBB changes in later stages of life. Additionally, this study only examined male rats, so it is unclear if there are any sex differences in BBB changes with age.

SCIENTIFIC POWER: MODERATE - This study provides important insight into age-dependent changes in the BBB. While the study is limited by its focus on only two age groups and male rats, it still provides a solid foundation for future research on the BBB and aging. The comprehensive approach used in this study also increases its scientific power.

Cai, Z., Qiao, P.F., Wan, C.Q., Cai, M., Zhou, N.K. and Li, Q., 2018. Role of blood-brain barrier in Alzheimer’s disease. Journal of Alzheimer's Disease, 63(4), pp.1223-1234.

OVERVIEW: This article explores the role of the blood-brain barrier in Alzheimer's disease. The blood-brain barrier is a protective layer that separates the brain from the blood and regulates the entry of substances from the blood into the brain. The article discusses how changes in the blood-brain barrier may contribute to the development and progression of Alzheimer's disease.

STRENGTHS: The article provides a comprehensive overview of the current research on the blood-brain barrier in Alzheimer's disease. It discusses both preclinical and clinical studies and provides insights into potential mechanisms underlying blood-brain barrier dysfunction in Alzheimer's disease. The article also discusses potential therapeutic targets to prevent or treat blood-brain barrier dysfunction in Alzheimer's disease.

LIMITATIONS: The article mainly focuses on preclinical and clinical studies, and some of the findings may not yet be applicable to human patients with Alzheimer's disease. Additionally, the article only discusses blood-brain barrier dysfunction as a potential contributor to Alzheimer's disease and does not cover other possible factors that may contribute to the disease.

SCIENTIFIC POWER: MODERATE - The article is based on a comprehensive review of the current research on the blood-brain barrier in Alzheimer's disease. However, further research is needed to confirm the findings discussed in the article and to fully understand the role of the blood-brain barrier in Alzheimer's disease.

Campos-Bedolla, P., Walter, F.R., Veszelka, S. and Deli, M.A., 2014. Role of the blood–brain barrier in the nutrition of the central nervous system. Archives of medical research, 45(8), pp.610-638.

OVERVIEW: The article reviews the essential functions of the BBB and how it contributes to the brain's nutritional needs.

STRENGTHS: The article provides comprehensive information on the BBB's structure and function, highlighting the barrier's critical role in the brain's nutrition. It discusses the various mechanisms by which the BBB regulates nutrient uptake and transport, such as transporter proteins, receptors, and efflux pumps. The article also explores the different nutrients that are necessary for brain function, including glucose, amino acids, and vitamins.

LIMITATIONS: The article mostly focuses on the BBB's nutritional function, and there is limited discussion on other essential roles, such as protecting the brain from harmful substances.

SCIENTIFIC POWER: MODERATE to STRONG - The authors have cited reliable sources and provided a comprehensive overview of the BBB's role in maintaining a healthy brain. Overall, the article provides valuable information on the BBB's nutritional function and its importance in maintaining a healthy brain. It is a useful resource for anyone interested in understanding how the BBB contributes to the brain's nutrient supply.

De Vries, H.E., Kuiper, J., De Boer, A.G., Van Berkel, T.J. and Breimer, D.D., 1997. The blood-brain barrier in neuroinflammatory diseases. Pharmacological Reviews, 49(2), pp.143-156.

OVERVIEW: This review article discusses the changes that occur in the BBB during neuroinflammation and the potential role of the BBB in the development and progression of these diseases.

STRENGTHS: The article provides a comprehensive overview of the changes that occur in the BBB during neuroinflammatory diseases and their potential impact on disease progression. The authors cite a large number of studies to support their claims, providing a strong evidence base for their conclusions. Additionally, the article highlights potential therapeutic targets for preventing or treating neuroinflammatory diseases by targeting the BBB.

LIMITATIONS: The article is somewhat dated, having been published in 1997, and may not reflect the latest findings on the topic. Additionally, some of the studies cited in the article were conducted in animal models, which may not accurately reflect the human BBB.

SCIENTIFIC POWER: MODERATE - While the article provides a thorough overview of the role of the BBB in neuroinflammatory diseases, it is limited by its age and reliance on animal studies. Nonetheless, it remains a valuable resource for understanding the potential involvement of the BBB in these diseases and the potential for therapeutic interventions targeting the BBB.

Domínguez, A., Álvarez, A., Hilario, E., Suarez-Merino, B. and Goñi-de-Cerio, F., 2013. Central nervous system diseases and the role of the blood-brain barrier in their treatment. Neurosci Discov, 1(1), p.3.

OVERVIEW: The article discusses the role of the blood-brain barrier (BBB) in the treatment of various central nervous system diseases. The BBB is a crucial barrier that protects the brain from harmful substances while allowing essential nutrients to pass through. However, this barrier can also prevent the delivery of therapeutic drugs to the brain.

STRENGTHS: The article provides a comprehensive overview of the current knowledge of the BBB and its role in central nervous system diseases. It highlights the challenges in developing effective treatments for these diseases due to the limited penetration of drugs through the BBB. The article also discusses various approaches to overcome these challenges, including the use of nanoparticles, cell-penetrating peptides, and drug delivery systems.

LIMITATIONS: The article does not provide a detailed discussion of the potential side effects of drug delivery methods that bypass the BBB. It also does not address the ethical concerns associated with the use of these methods.

SCIENTIFIC POWER: MODERATE - The article provides a good overview of the current state of knowledge about the BBB and its role in the treatment of central nervous system diseases. However, it does not present any new findings or original research. Overall, the article is a useful resource for understanding the role of the BBB in the treatment of central nervous system diseases and the challenges in developing effective therapies. However, more research is needed to fully understand the potential risks and benefits of various drug delivery methods that bypass the BBB.

Erickson, M. A. & Banks, W. A., 2013. Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer’s Disease. Journal of Cerebral Blood Flow & Metabolism. [Online] 33 (10), 1500–1513.

OVERVIEW: This review article focuses on the role of the blood-brain barrier in Alzheimer's disease, both as a cause and consequence of the disease. The blood-brain barrier is a complex system of blood vessels and cells that protect the brain from harmful substances while allowing essential nutrients and oxygen to pass through. Dysfunction of this barrier has been linked to Alzheimer's disease.

STRENGTHS: The article provides a comprehensive overview of the blood-brain barrier and its role in Alzheimer's disease. It highlights the latest research findings, including studies that suggest that blood-brain barrier dysfunction is a key factor in the development and progression of Alzheimer's disease. The authors also discuss potential therapeutic strategies for treating Alzheimer's disease by targeting the blood-brain barrier.

LIMITATIONS: The article mainly focuses on the role of the blood-brain barrier in Alzheimer's disease and does not provide an in-depth analysis of other factors that contribute to the disease's development and progression. The authors also acknowledge that many of the studies they cited were conducted in animal models and that more research is needed to understand how these findings translate to humans.

SCIENTIFIC POWER: STRONG – It draws on numerous studies and provides a comprehensive overview of the current understanding of the blood-brain barrier in Alzheimer's disease. The authors also discuss potential therapeutic strategies for treating Alzheimer's disease, which could be of significant interest to researchers and clinicians working in the field. However, as the authors themselves note, more research is needed to fully understand the complex relationship between blood-brain barrier dysfunction and Alzheimer's disease.

Erickson, M.A. and Banks, W.A., 2019. Age-associated changes in the immune system and blood–brain barrier functions. International journal of molecular sciences, 20(7), p.1632.

OVERVIEW: The article discusses the changes that occur in the immune system and the blood-brain barrier (BBB) as we age. The BBB is a protective barrier that prevents harmful substances from entering the brain, and it is maintained by specialized cells called endothelial cells. As we age, the immune system and endothelial cells become less efficient, leading to BBB dysfunction.

STRENGTHS: The article provides a comprehensive overview of the changes that occur in the immune system and BBB as we age. The authors use a variety of studies to support their arguments and provide helpful diagrams to explain complex concepts.

LIMITATIONS: While the article does a good job of summarising the current state of research, it does not provide any new experimental data. Additionally, the article only focuses on age-related changes in the immune system and BBB and does not discuss other factors that may contribute to BBB dysfunction, such as chronic diseases or environmental toxins.

SCIENTIFIC POWER: MODERATE to STRONG - The article provides a comprehensive overview of the current research on age-related changes in the immune system and BBB function. The authors use a variety of studies to support their arguments and provide helpful diagrams to explain complex concepts. However, the article does not provide any new experimental data, and the authors acknowledge that more research is needed to fully understand the mechanisms behind BBB dysfunction in aging.

Faraco, G., Park, L., Zhou, P., Luo, W., Paul, S.M., Anrather, J. and Iadecola, C., 2016. Hypertension enhances A β-induced neurovascular dysfunction, promotes β-secretase activity, and leads to amyloidogenic processing of APP. Journal of Cerebral Blood Flow & Metabolism, 36(1), pp.241-252.

OVERVIEW: The article discusses how high blood pressure, also known as hypertension, can contribute to the development of Alzheimer’s disease. The study showed that high blood pressure can cause dysfunction in the blood vessels of the brain, leading to the accumulation of harmful proteins called amyloid beta (Aβ) and increased activity of beta-secretase, an enzyme involved in the production of Aβ. These changes can lead to the amyloidogenic processing of amyloid precursor protein (APP), which is a hallmark of Alzheimer’s disease.

STRENGTHS: The study. is important because it sheds light on a previously unknown link between hypertension and Alzheimer’s disease. The study used an animal model of hypertension and Alzheimer’s disease, which allowed the researchers to closely examine the effects of high blood pressure on the brain. The study also used multiple techniques, including in vivo imaging and molecular biology assays, to analyse the changes in the brain caused by hypertension.

LIMITATIONS: While the animal model used in this study provides valuable insights into the mechanisms underlying the link between hypertension and Alzheimer’s disease, it is important to note that animal studies cannot always be directly translated to humans. Additionally, the study did not examine the effects of lowering blood pressure on the development of Alzheimer’s disease, so further research is needed to determine whether treating hypertension could prevent or delay the onset of Alzheimer’s disease.

SCIENTIFIC POWER: MODERATE to STRONG -The study provides novel insights into the mechanisms underlying the link between hypertension and Alzheimer’s disease and uses multiple techniques to analyse the changes in the brain caused by hypertension. However, the study is limited by the use of an animal model and the lack of investigation into the effects of blood pressure-lowering treatments on the development of Alzheimer’s disease in humans.

Fenstermacher, J.D., Nagaraja, T. and Davies, K.R., 2001. Overview of the structure and function of the blood-brain barrier in vivo. Blood—Brain barrier: Drug Delivery and Brain Pathology, pp.1-7.

OVERVIEW: This article provides a comprehensive overview of the structure and function of the blood-brain barrier in vivo, which means that the research was conducted in living organisms.

STRENGTHS: The authors explain the importance of the blood-brain barrier and how it works to protect the brain from harmful substances. They also discuss the different types of cells that make up the blood-brain barrier and how they contribute to its function. This article is a great resource for anyone interested in learning about the blood-brain barrier and its role in brain health.

LIMITATIONS: This article is an overview and does not provide in-depth analysis of specific diseases or treatments. While the authors explain the structure and function of the blood-brain barrier in detail, they do not discuss its role in specific disease processes or the potential limitations of the blood-brain barrier as a drug delivery system. Additionally, this article was published in 2001, and more recent research has expanded our understanding of the blood-brain barrier.

SCIENTIFIC POWER: MODERATE to STRONG - While it is not a primary research article, it provides a comprehensive overview of the blood-brain barrier in vivo and includes references to relevant studies. The authors are experts in the field of neuroscience and provide a clear and concise explanation of the blood-brain barrier and its importance. However, as mentioned, this article was published in 2001, and more recent research has expanded our knowledge of the topic.

Gloor, S.M., Wachtel, M., Bolliger, M.F., Ishihara, H., Landmann, R. and Frei, K., 2001. Molecular and cellular permeability control at the blood–brain barrier. Brain Research Reviews, 36(2-3), pp.258-264.

OVERVIEW: Gloor et al. (2001) review the molecular and cellular mechanisms that regulate the BBB's permeability. They describe how specialized cells called astrocytes and pericytes work together with endothelial cells to form the BBB. These cells communicate with each other through chemical signals to control the passage of substances into and out of the brain. The authors also discuss how BBB dysfunction can contribute to neurological disorders such as Alzheimer's disease, multiple sclerosis, and brain tumours.

STRENGTHS: Gloor et al. provide a comprehensive overview of the molecular and cellular mechanisms involved in BBB permeability control. They use clear language and provide helpful diagrams to explain complex concepts. The article also includes a thorough review of the literature on BBB dysfunction in neurological disorders.

LIMITATIONS: The article is somewhat outdated, as it was published over 20 years ago. Since then, there have been many new discoveries in the field of BBB research, and the mechanisms described in this article may have been refined or revised. Additionally, the article does not delve deeply into the specific molecular mechanisms of BBB permeability control, instead focusing on a general overview.

SCIENTIFIC POWER: MODERATE to STRONG - While it may be somewhat outdated, it provides a solid foundation for understanding the molecular and cellular mechanisms involved in BBB permeability control. The article is well-cited and draws on a large body of research.

Haddad-Tóvolli, R., Dragano, N.R., Ramalho, A.F. and Velloso, L.A., 2017. Development and function of the blood-brain barrier in the context of metabolic control. Frontiers in Neuroscience, 11, p.224.

OVERVIEW: This review discusses the development and function of the BBB in the context of metabolic control. Metabolic control involves the regulation of metabolism, which is the process by which the body converts food into energy. The BBB plays an important role in metabolic control by regulating the entry of nutrients and hormones into the brain.

STRENGTHS: This review provides a detailed overview of the development and function of the BBB, highlighting the importance of the BBB in regulating metabolic control. It also discusses the role of specific molecules and cell types in the development and maintenance of the BBB.

LIMITATIONS: The review focuses primarily on animal studies, and the relevance of the findings to human physiology and disease is not fully explored. Additionally, the review does not discuss potential limitations or challenges associated with targeting the BBB for therapeutic interventions.

SCIENTIFIC POWER: MODERATE - While the review provides a comprehensive overview of the current understanding of BBB development and function in the context of metabolic control, further studies are needed to fully understand the complex interactions between the BBB and metabolic pathways, as well as the implications for disease and therapeutic interventions.

Haseloff, R.F., Dithmer, S., Winkler, L., Wolburg, H. and Blasig, I.E., 2015, February. Transmembrane proteins of the tight junctions at the blood–brain barrier: structural and functional aspects. In Seminars in Cell & Developmental Biology (Vol. 38, pp. 16-25). Academic Press.

OVERVIEW: This article explores the transmembrane proteins found in these tight junctions and their structural and functional aspects.

STRENGTHS: The article provides a detailed overview of the molecular and cellular components of the blood-brain barrier, particularly focusing on the tight junctions. It includes numerous diagrams and figures that illustrate the complex structure of the tight junctions and how they function. The article also discusses how these proteins contribute to the overall function of the blood-brain barrier.

LIMITATIONS: The article can be quite technical and may be challenging for some readers to understand, particularly those without a strong background in biology or biochemistry. Additionally, the article only focuses on the tight junctions' role in the blood-brain barrier, and other important aspects, such as transport mechanisms and cellular signalling, are not discussed in depth.

SCIENTIFIC POWER: MODERATE to STRONG - The authors have conducted extensive research on the structural and functional aspects of the transmembrane proteins found in the tight junctions of the blood-brain barrier. However, the article does not present any new experimental data or findings, but rather, it synthesises and summarises existing knowledge in the field. Overall, this article provides valuable insights into the blood-brain barrier's molecular and cellular components, particularly the transmembrane proteins found in the tight junctions. It serves as a useful resource for those interested in understanding the blood-brain barrier's essential functions and its contribution to brain health and disease.

Hawkins, R.A., O'Kane, R.L., Simpson, I.A. and Vina, J.R., 2006. Structure of the blood–brain barrier and its role in the transport of amino acids. The Journal of Nutrition, 136(1), pp.218S-226S.

OVERVIEW: The article explores the structure and function of the blood-brain barrier (BBB) in relation to the transport of amino acids. The BBB is a protective membrane that separates the brain from the rest of the body and regulates the movement of molecules and cells in and out of the brain. Amino acids are essential molecules for brain function and are transported across the BBB by specific transporters. The article discusses the different types of transporters and their roles in maintaining amino acid levels in the brain.

STRENGTHS: The article provides a detailed overview of the structure and function of the BBB and its role in the transport of amino acids. It also discusses the different types of transporters and their functions, which is important for understanding how amino acids are regulated in the brain. The information provided can help researchers develop new therapies for brain disorders that involve amino acid imbalances.

LIMITATIONS: The article focuses specifically on the transport of amino acids and does not provide an overview of other molecules that are transported across the BBB. Additionally, the article does not discuss the impact of BBB dysfunction on amino acid transport, which is important for understanding the pathophysiology of brain disorders.

SCIENTIFIC POWER: MODERATE - The authors provide a comprehensive overview of the current understanding of amino acid transport across the BBB, but the article does not provide new experimental data. The article is a review of the existing literature on the topic and does not include new experiments or analyses. Overall, the article provides valuable information for researchers studying amino acid transport in the brain.

Huber, J.D., 2008. Diabetes, cognitive function, and the blood-brain barrier. Current Pharmaceutical Design, 14(16), pp.1594-1600.

OVERVIEW: The article discusses the relationship between diabetes and cognitive function, particularly in relation to the blood-brain barrier (BBB). The BBB is a protective barrier between the brain and the blood that regulates what substances can enter the brain. When this barrier is damaged or compromised, it can affect brain function, including cognitive abilities like memory and learning. The article explores the mechanisms behind the effects of diabetes on the BBB and cognitive function.

STRENGTHS: The article provides a thorough overview of the current research on the topic and highlights the importance of understanding the relationship between diabetes and cognitive function. It discusses the possible mechanisms behind the effects of diabetes on the BBB and cognitive function and provides potential treatment strategies.

LIMITATIONS: The article mainly focuses on animal studies, so it is unclear how well the findings translate to humans. The article does not explore the possibility of reverse causality, i.e., whether cognitive decline may lead to diabetes or if diabetes leads to cognitive decline.

SCIENTIFIC POWER: MODERATE - While the article provides a good overview of the current research on the topic, it mainly focuses on animal studies, so more research is needed to determine how well the findings translate to humans. Additionally, the article does not explore other factors that may contribute to the relationship between diabetes and cognitive function. However, the article does provide potential treatment strategies that may help improve cognitive function in individuals with diabetes.

Jin, J., Fang, F., Gao, W., Chen, H., Wen, J., Wen, X. and Chen, J., 2021. The structure and function of the glycocalyx and its connection with blood-brain barrier. Frontiers in Cellular Neuroscience, 15, p.739699.

OVERVIEW: The article focuses on the glycocalyx, which is a layer of sugar molecules that covers the surface of cells in the body, including those in the blood-brain barrier (BBB). The BBB is a specialized network of cells and blood vessels that protect the brain from harmful substances while allowing essential nutrients and oxygen to pass through. The article discusses how the glycocalyx is involved in the function of the BBB and how disruptions to its structure and function may contribute to brain diseases.

STRENGTHS: The article provides a comprehensive review of the research on the glycocalyx and its connection to the BBB. It covers both the structural and functional aspects of the glycocalyx and includes information on how it interacts with different types of cells in the BBB. The article also discusses how the glycocalyx may be involved in the pathogenesis of brain diseases such as Alzheimer's disease.

LIMITATIONS: The article is a review article and does not present any original research. It also does not provide a detailed discussion of the methods used in the studies that it cites.

SCIENTIFIC POWER: MODERATE to STRONG - The article provides a comprehensive overview of the current understanding of the glycocalyx and its connection to the BBB. However, because it is a review article, it does not present any new data or experimental findings. Nonetheless, the article is useful for researchers interested in the role of the glycocalyx in the BBB and its potential involvement in brain diseases.

Kadry, H., Noorani, B. and Cucullo, L., 2020. A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids and Barriers of the CNS, 17(1), pp.1-24.

OVERVIEW: In this article, the authors provide an overview of the BBB, including its structure, function, impairment, and biomarkers of integrity. They also discuss various techniques to evaluate BBB dysfunction and current research on BBB-targeted drug delivery.

STRENGTHS: This article provides a comprehensive and detailed overview of the BBB, making it an excellent resource for anyone looking to understand this critical structure. The authors also discuss various techniques to evaluate BBB integrity, which is crucial for diagnosing and treating BBB-related diseases. Additionally, they cover current research on BBB-targeted drug delivery, which could lead to more effective treatments for brain-related disorders.

LIMITATIONS: While this article provides a comprehensive overview of the BBB, it can be quite technical, which may be challenging for those without a scientific background. Additionally, while the authors discuss several biomarkers of BBB integrity, they do not go into detail about their specific functions or limitations.

SCIENTIFIC POWER: MODERATE to STRONG - It provides a detailed and up-to-date overview of the BBB and its functions. The authors use a variety of sources to support their claims and provide evidence for their conclusions.

Keaney, J. and Campbell, M., 2015. The dynamic blood–brain barrier. The FEBS Journal, 282(21), pp.4067-4079.

OVERVIEW: This article provides a comprehensive overview of the BBB and its role in protecting the brain. It discusses the various cell types and tight junctions that make up the BBB and how they function together to create a barrier.

STRENGTHS: The article highlights recent research that has advanced our understanding of the dynamic nature of the BBB and how it can be influenced by changes in the body.

LIMITATIONS: While this article provides a thorough overview of the BBB, it does not delve into specific diseases or conditions that affect the BBB.

SCIENTIFIC POWER: MODERATE to STRONG - It provides a comprehensive overview of the BBB and draws on recent research to highlight the dynamic nature of the barrier. While it does not present new research findings, it synthesises existing knowledge in a clear and accessible manner.

Langen, U.H., Ayloo, S. and Gu, C., 2019. Development and cell biology of the blood-brain barrier. Annual Review of Cell and Developmental Biology, 35, pp.591-613.

OVERVIEW: In this review, Langen et al. discuss the development and cell biology of the BBB, including the formation and maintenance of tight junctions, the role of pericytes and astrocytes in BBB function, and the molecular mechanisms involved in BBB development.

STRENGTHS: The review provides a comprehensive overview of the current understanding of BBB development and cell biology, including both established knowledge and recent discoveries. The authors use clear and concise language to explain complex concepts and include helpful diagrams and figures to aid in understanding.

LIMITATIONS: The review focuses primarily on the basic science of BBB development and cell biology, with less emphasis on clinical applications or disease states that involve BBB dysfunction.

SCIENTIFIC POWER: MODERATE to STRONG - The authors draw from a wide range of primary research articles and provide a thorough synthesis of the current understanding of BBB development and cell biology. However, the review does not include original research or present new data.

Ma, F., Zhang, X. and Yin, K.J., 2020. MicroRNAs in central nervous system diseases: A prospective role in regulating blood-brain barrier integrity. Experimental Neurology, 323, p.113094.

OVERVIEW: This article discusses the role of small RNA molecules called microRNAs in the regulation of blood-brain barrier (BBB) integrity in central nervous system diseases. The BBB is a highly selective membrane that separates the brain from the bloodstream and protects it from harmful substances. However, in certain neurological disorders, the BBB can become compromised, allowing toxins and immune cells to enter the brain and cause damage. The authors propose that microRNAs could be potential therapeutic targets for preventing BBB dysfunction in these diseases.

STRENGTHS: The article provides a comprehensive overview of the current understanding of microRNAs and their role in BBB regulation, supported by several research studies. It highlights the potential of microRNAs as targets for therapeutic interventions to prevent or treat BBB dysfunction in neurological disorders. The authors also provide a detailed discussion of the mechanisms by which microRNAs regulate BBB integrity and the various signalling pathways involved.

LIMITATIONS: The article primarily focuses on preclinical research studies and animal models, and there is limited clinical data on the use of microRNAs as therapeutic targets for BBB dysfunction in humans. Additionally, the article does not provide a detailed discussion of potential side effects or safety concerns associated with the use of microRNAs as therapeutic targets.

SCIENTIFIC POWER: MODERATE to STRONG - The authors provide a well-supported overview of the current research on microRNAs and BBB regulation and propose a promising new therapeutic avenue for treating neurological disorders. However, as mentioned, the article primarily focuses on preclinical research and more clinical data is needed to fully evaluate the potential of microRNAs as therapeutic targets.

Mooradian, A.D., 1988. Effect of aging on the blood-brain barrier. Neurobiology of Aging, 9, pp.31-39.

OVERVIEW: This review article examines how ageing affects the BBB and what implications this may have for brain health.

STRENGTHS: The article provides a comprehensive overview of the current knowledge on the effect of ageing on the BBB. It discusses the changes that occur in the structure and function of the BBB with ageing and highlights the importance of understanding these changes in the context of neurological diseases.

LIMITATIONS: The article is based on a review of existing research and given it was published in 1988, does not present any new data or experiments. It is also limited in that it does not delve into the molecular mechanisms underlying the changes in the BBB with ageing.

SCIENTIFIC POWER: MODERATE - It is a review article that synthesizes existing research on the topic of ageing and the BBB. The research presented in the article is mainly based on animal studies, which may not necessarily translate to humans. Nonetheless, the article provides valuable insights into the relationship between ageing and the BBB and highlights the need for further research in this area. In summary, this article provides an overview of how ageing affects the BBB and highlights the importance of this knowledge for brain health. While it is based on existing research and does not present any new data or experiments, it provides valuable insights into the topic and highlights the need for further research.

Neuwelt, E.A. ed., 2013. Implications of the Blood-Brain Barrier and Its Manipulation: Volume 1 Basic Science Aspects. Springer Science & Business Media.

OVERVIEW: In this book, various experts discuss the fundamental science behind the BBB and its potential for manipulation in the treatment of brain disorders.

STRENGTHS: The book provides a comprehensive overview of the BBB and its role in protecting the brain. It covers a wide range of topics, from the basic anatomy and physiology of the BBB to the latest research on BBB manipulation. The various authors are experts in their fields and offer insights into the complex workings of the BBB.

LIMITATIONS: The book is quite technical and may be difficult for those without a strong background in neuroscience or biology to fully comprehend. It also only covers the basic science aspects of BBB manipulation and does not delve into the clinical applications or ethical considerations.

SCIENTIFIC POWER: MODERATE to STRONG - It presents a detailed analysis of the BBB and its potential for manipulation, drawing on the latest research in the field. However, the book is limited by its focus on the basic science aspects of BBB manipulation and does not address the clinical or ethical implications.

Overall, "Implications of the Blood-Brain Barrier and Its Manipulation: Volume 1 Basic Science Aspects" is a valuable resource for those interested in understanding the complex workings of the BBB and its potential for manipulation in the treatment of brain disorders.

Obermeier, B., Daneman, R. and Ransohoff, R.M., 2013. Development, maintenance and disruption of the blood-brain barrier. Nature Medicine, 19(12), pp.1584-1596.

OVERVIEW: This review article discusses the development, maintenance, and disruption of the BBB. The authors explain how the BBB is formed during development, how it is maintained throughout life, and how it can be disrupted in various diseases. They also discuss current research aimed at better understanding the BBB and developing treatments for BBB-related disorders.

STRENGTHS: This article provides a comprehensive overview of the BBB and its role in protecting the brain. The authors draw from a large body of research to explain the development, maintenance, and disruption of the BBB. They also highlight the importance of ongoing research to better understand the BBB and develop treatments for BBB-related disorders.

LIMITATIONS: As with any review article, the authors must necessarily condense a large body of research into a limited space. This can make it difficult to fully explore certain topics or to provide detailed information on specific studies. Additionally, while the authors discuss various diseases that can disrupt the BBB, they do not provide an exhaustive list or a detailed discussion of each condition.

SCIENTIFIC POWER: STRONG - The authors draw from a large body of research to provide a comprehensive overview of the BBB and its role in protecting the brain. They also highlight ongoing research aimed at better understanding the BBB and developing treatments for BBB-related disorders. The article is published in a reputable journal and is authored by respected experts in the field of BBB research.

Obermeier, B., Verma, A. and Ransohoff, R.M., 2016. The blood–brain barrier. Handbook of Clinical Neurology, 133, pp.39-59.

OVERVIEW: In this article, the authors provide an overview of the blood-brain barrier, including its structure, function, and regulation.

STRENGTHS: The article provides a comprehensive review of the blood-brain barrier, covering the latest research findings, as well as historical information. It offers insights into the mechanisms underlying blood-brain barrier function, including the roles of specific proteins, and signalling pathways.

LIMITATIONS: The article is quite technical and may be difficult for non-experts to understand. It is also limited in that it only covers the blood-brain barrier from a clinical perspective and does not delve into its implications for basic research.

SCIENTIFIC POWER: MODERATE to STRONG - It draws on a wide range of studies from the last several decades, including both basic science and clinical research. The authors are experts in the field and offer their own insights into the mechanisms underlying blood-brain barrier function. While the article is technical, it is a valuable resource for researchers and clinicians seeking to better understand the blood-brain barrier and its role in health and disease.

Palmer, A.M., 2011. The role of the blood brain barrier in neurodegenerative disorders and their treatment. Journal of Alzheimer's Disease, 24(4), pp.643-656.

OVERVIEW: In neurodegenerative disorders like Alzheimer's disease, the BBB may become compromised, allowing toxic substances to enter the brain and contribute to neuronal damage. This review article discusses the role of the BBB in neurodegenerative disorders and how targeting the BBB may provide new treatments for these diseases.

STRENGTHS: The article provides a comprehensive overview of the BBB and its role in neurodegenerative disorders. It discusses the mechanisms by which the BBB becomes compromised in these diseases, as well as potential therapies that target the BBB to prevent or slow disease progression. The author uses both animal and human studies to support their arguments, making the article well-rounded and informative.

LIMITATIONS: The article focuses primarily on Alzheimer's disease, with little discussion of other neurodegenerative disorders. Additionally, the author primarily discusses the potential of BBB-targeting therapies rather than current treatments, which may limit the practical application of the article's findings.

SCIENTIFIC POWER: MODERATE to STRONG - The author uses a variety of studies to support their arguments, including animal models and clinical trials. However, the article primarily focuses on potential therapies rather than current treatments, which may limit its immediate impact on clinical practice.

Pandit, R., Chen, L. and Götz, J., 2020. The blood-brain barrier: Physiology and strategies for drug delivery. Advanced Drug Delivery Reviews, 165, pp.1-14.

OVERVIEW: The blood-brain barrier’s primary function is to prevent harmful substances from entering the brain and causing damage. However, this also makes it difficult for drugs to reach the brain and treat neurological disorders. In this article, the authors discuss the physiology of the BBB and strategies to overcome its challenges for drug delivery.

STRENGTHS: This article provides a comprehensive overview of the BBB and the challenges it presents for drug delivery. The authors discuss various strategies for drug delivery such as disrupting the BBB using ultrasound, using nanoparticles to target the brain, and modifying drugs to make them more effective at crossing the BBB. The article also provides insights into the physiology of the BBB and the mechanisms that regulate its permeability.

LIMITATIONS: The article primarily focuses on the strategies for drug delivery and may not provide an in-depth analysis of the underlying mechanisms that regulate BBB permeability. Additionally, some of the strategies discussed are still in the experimental stage and may not be feasible for clinical use in the near future.

SCIENTIFIC POWER: MODERATE to STRONG - The authors provide a thorough review of the BBB and strategies for drug delivery, supported by a range of experimental and clinical studies. However, as drug delivery to the brain is a complex field, further research is necessary to fully understand the mechanisms of BBB permeability and develop effective strategies for drug delivery.

Persidsky, Y., Ramirez, S.H., Haorah, J. and Kanmogne, G.D., 2006. Blood–brain barrier: structural components and function under physiologic and pathologic conditions. Journal of Neuroimmune Pharmacology, 1, pp.223-236.

OVERVIEW: This article discusses the components of the BBB and how they function under normal and diseased conditions.

STRENGTHS: The article provides a detailed overview of the different structural components of the BBB and their functions. It also highlights the importance of the BBB in maintaining the proper functioning of the brain and nervous system. The authors provide insight into how the BBB is affected by various pathologic conditions, such as HIV infection and stroke.

LIMITATIONS: The article is somewhat technical and may be difficult for non-scientific readers to fully understand. It does not provide a lot of practical advice on how to treat or prevent BBB dysfunction.

SCIENTIFIC POWER: MODERATE to STRONG - The authors provide a comprehensive review of the current understanding of the BBB, drawing on a large body of research. However, some of the information presented may be outdated, as the article was published in 2006. Overall, this article is a useful resource for those interested in understanding the structure and function of the BBB, particularly as it relates to neurological diseases.

Reed, M.J., Damodarasamy, M. and Banks, W.A., 2019. The extracellular matrix of the blood–brain barrier: structural and functional roles in health, aging, and Alzheimer’s disease. Tissue Barriers, 7(4), p.1651157.

OVERVIEW: The blood-brain barrier (BBB) is a protective barrier that separates the brain from the blood and maintains a stable environment for the proper functioning of the brain. The extracellular matrix (ECM) is a complex network of proteins that surrounds the cells of the BBB and plays a critical role in regulating its structural and functional integrity. The article by Reed et al. (2019) focuses on the role of the ECM in maintaining the BBB and its contribution to the pathogenesis of aging and neurodegenerative diseases such as Alzheimer's disease.

STRENGTHS: The article provides a comprehensive review of the current understanding of the ECM in the BBB, including its composition, function, and regulation. It highlights the critical role of the ECM in maintaining the structural and functional integrity of the BBB, which is essential for the proper functioning of the brain. The article also discusses the potential involvement of the ECM in the pathogenesis of neurodegenerative diseases, providing valuable insights into the underlying mechanisms of disease development.

LIMITATIONS: While the article provides a detailed overview of the ECM and its role in the BBB, it is a review article that summarizes the existing literature rather than presenting new data. Additionally, the article focuses primarily on Alzheimer's disease and does not cover the potential involvement of the ECM in other neurodegenerative diseases.

SCIENTIFIC POWER: MODERATE to STRONG - The article is based on a thorough review of the current literature on the subject, providing a detailed understanding of the role of the ECM in maintaining the BBB's structural and functional integrity. However, as a review article, it does not present new experimental data. Nonetheless, the article offers insights into the potential therapeutic targets for neurodegenerative diseases that involve the ECM in the BBB.

Rhea, E.M., Salameh, T.S., Logsdon, A.F., Hanson, A.J., Erickson, M.A. and Banks, W.A., 2017. Blood-brain barriers in obesity. The AAPS Journal, 19, pp.921-930.

OVERVIEW: In this article, the authors investigate how obesity can affect the function of the BBB. They discuss how changes in the BBB can contribute to the development of neurological diseases in obese individuals.

STRENGTHS: This article provides new insights into the relationship between obesity and the BBB. It presents data from both animal and human studies and uses a variety of techniques to investigate changes in the BBB function.

LIMITATIONS: The studies discussed in this article are mainly observational and cannot establish a causal relationship between obesity and BBB dysfunction. The authors also acknowledge that the mechanisms underlying BBB changes in obesity are not well understood and require further investigation.

SCIENTIFIC POWER: MODERATE to STRONG - While the studies presented provide important insights into the effects of obesity on the BBB, more research is needed to fully understand the mechanisms involved and to develop effective treatments for obesity-related neurological disorders. Overall, this article highlights the importance of maintaining a healthy weight and lifestyle to reduce the risk of developing neurological disorders associated with BBB dysfunction. It emphasizes the need for continued research to better understand the relationship between obesity and BBB function and to develop effective interventions.

Serlin, Y., Shelef, I., Knyazer, B. and Friedman, A., 2015, February. Anatomy and physiology of the blood–brain barrier. In Seminars in cell & developmental biology (Vol. 38, pp. 2-6). Academic Press.

OVERVIEW: This article provides a concise and easy-to-understand overview of the anatomy and physiology of the BBB.

STRENGTHS: It covers the basic structure of the BBB, including the role of endothelial cells and astrocytes, and highlights the key functions of the BBB. The article also briefly touches on the importance of the BBB in neurological disorders and potential ways to target the BBB for drug delivery.

LIMITATIONS: As a brief overview article, this paper does not go into great detail about the complex mechanisms that regulate BBB function or the latest research on the BBB. It also does not discuss some of the challenges associated with drug delivery across the BBB or the potential risks associated with BBB disruption.

SCIENTIFIC POWER: MODERATE - It provides a good introduction to the BBB but lacks in-depth analysis or discussion of recent research.

Tajes, M., Ramos-Fernández, E., Weng-Jiang, X., Bosch-Morato, M., Guivernau, B., Eraso-Pichot, A., Salvador, B., Fernandez-Busquets, X., Roquer, J. and Munoz, F.J., 2014. The blood-brain barrier: structure, function and therapeutic approaches to cross it. Molecular Membrane Biology, 31(5), pp.152-167.

OVERVIEW: This review article discusses the structure and function of the blood-brain barrier, as well as different therapeutic approaches that can be used to bypass it.

STRENGTHS: This article provides a comprehensive overview of the blood-brain barrier and its importance in protecting the brain from harmful substances. It also discusses various strategies that can be used to deliver drugs to the brain, including nanoparticles and other carrier systems. The authors provide detailed explanations and illustrations to help readers understand the complex mechanisms involved in the blood-brain barrier.

LIMITATIONS: One limitation of this article is that it is quite technical and may be difficult for some readers to understand without prior knowledge of the topic. Additionally, while the authors discuss different therapeutic approaches to bypass the blood-brain barrier, they do not provide an in-depth analysis of the effectiveness or safety of these methods.

SCIENTIFIC POWER: MODERATE to STRONG - This review article provides a detailed and informative overview of the blood-brain barrier, its structure, and its functions. It also discusses different approaches to overcome this barrier for drug delivery. However, more research is needed to fully understand the effectiveness and safety of these approaches.

Varatharaj, A. and Galea, I., 2017. The blood-brain barrier in systemic inflammation. Brain, Behavior, and Immunity, 60, pp.1-12.

OVERVIEW: This article specifically focuses on how systemic inflammation, which is inflammation that affects the entire body, can impact the function of the blood-brain barrier.

STRENGTHS: This article provides a comprehensive review of the current understanding of how systemic inflammation can disrupt the blood-brain barrier. The authors discuss the various mechanisms involved, including the release of inflammatory molecules, the activation of immune cells, and the alteration of the structure of the barrier. The article also highlights the implications of a compromised blood-brain barrier in the context of various diseases, such as multiple sclerosis, Alzheimer's disease, and stroke.

LIMITATIONS: While the article presents a thorough review of the topic, it does not provide any new experimental data or findings. Instead, it is a compilation of existing research on the subject.

SCIENTIFIC POWER: MODERATE to STRONG - It draws on a wide range of studies and reviews, presenting a well-supported and detailed overview of the current understanding of the impact of systemic inflammation on the blood-brain barrier. However, it does not provide any new experimental data or insights, and some of the mechanisms discussed remain to be fully understood.

Wong, A.D., Ye, M., Levy, A.F., Rothstein, J.D., Bergles, D.E. and Searson, P.C., 2013. The blood-brain barrier: an engineering perspective. Frontiers in Neuroengineering, 6, p.7.

OVERVIEW: Wong et al. (2013) discuss the BBB from an engineering perspective, highlighting the importance of understanding the BBB's structure and function to develop new treatments for brain disorders.

STRENGTHS: The article is well-written and easy to understand. It offers a unique perspective on the BBB as an engineering challenge, and the authors provide clear examples of how engineering principles can be applied to improve our understanding and treatment of brain disorders. The article includes useful figures and tables to illustrate key points.

LIMITATIONS: The article focuses primarily on engineering approaches to understanding the BBB and may not be as useful for readers interested in other aspects of BBB research. The article also does not cover some of the latest research on the BBB, as it was published in 2013.

SCIENTIFIC POWER: MODERATE - It provides a useful overview of the BBB and its importance in brain function and disease. The engineering perspective is a unique and valuable contribution to the field, but the article is not comprehensive and may not provide the most up-to-date information on BBB research.

Zhao, Z., Nelson, A.R., Betsholtz, C. and Zlokovic, B.V., 2015. Establishment and dysfunction of the blood-brain barrier. Cell, 163(5), pp.1064-1078.

OVERVIEW: The blood-brain barrier (BBB) is a specialized structure that separates the blood circulating in the body from the brain's extracellular fluid, protecting the brain from harmful substances while allowing necessary nutrients to enter. This article discusses the establishment and dysfunction of the BBB, including the molecular and cellular mechanisms involved.

STRENGTHS: This article provides a comprehensive overview of the BBB, including its development and the various cell types involved in its maintenance. It discusses in detail the molecular components of the BBB, such as tight junction proteins and transporters, which play important roles in regulating the movement of substances between the blood and brain.

LIMITATIONS: The article can be complex, as it includes technical terms and molecular mechanisms that may require some background knowledge in biology and neuroscience. The article also focuses mainly on the molecular and cellular aspects of the BBB and may not provide a complete understanding of the BBB's physiology and function in the context of neurological disorders.

SCIENTIFIC POWER: STRONG - It provides a detailed and up-to-date understanding of the establishment and dysfunction of the BBB. The authors have extensively reviewed the literature and incorporated recent findings into their discussion, providing a comprehensive overview of the BBB's molecular and cellular mechanisms. The article also highlights the BBB's importance in the pathogenesis of neurological disorders, making it a valuable resource for researchers studying BBB dysfunction in disease.