Blood-Brain Barrier: From Physiology to Disease and Back.
By Melanie D. Sweeney, Zhen Zhao, Axel Montagne, Amy R. Nelson, Berislav Zlokovic. Physiological Reviews, 2019
1,890 citations recorded by the source corpus.
The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells, and pathogens from entering the brain. At the same time, the BBB regulates transport of molecules into and out of the central nervous system (CNS), which maintains tightly controlled chemical composition of the neuronal milieu that is required for proper neuronal functioning. In this review, we first examine molecular and cellular mechanisms underlying the establishment of the BBB. Then, we focus on BBB transport physiology, endothelial and pericyte transporters, and perivascular and paravascular transport. Next, we discuss rare human monogenic neurological disorders with the primary genetic defect in BBB-associated cells demonstrating the link between BBB breakdown and neurodegeneration. Then, we review the effects of genes underlying inheritance and/or increased susceptibility for Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, and amyotrophic lateral sclerosis (ALS) on BBB in relation to other pathologies and neurological deficits. We next examine how BBB dysfunction relates to neurological deficits and other pathologies in the majority of sporadic AD, PD, and ALS cases, multiple sclerosis, other neurodegenerative disorders, and acute CNS disorders such as stroke, traumatic brain injury, spinal cord injury, and epilepsy. Lastly, we discuss BBB-based therapeutic opportunities. We conclude with lessons learned and future directions, with emphasis on technological advances to investigate the BBB functions in the living human brain, and at the molecular and cellular level, and address key unanswered questions.
Subfields: Endocrine and Autonomic Systems, Neurology
View Paper: https://www.semanticscholar.org/paper/791bca95f0b8dd8e5dfd4efb4aaa20ad54e1cf60
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Endocrine and Autonomic Systems
In Neurology
- C. Iadecola
- Martin Dichgans
- Julie A. Schneider
- Vladimir Hachinski
- Behnam Noorani
- L. Cucullo
- Hossam Kadry
- Berislav Zlokovic
Citations in the corpus
- Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020, background): “Decreased cerebral blood flow, coupled with increased Aβ levels induced by BBB deterioration can also aggravate tau pathology [628, 629].”
- The blood–brain barrier: Structure, regulation and drug delivery (2023, background): “131 Intriguingly, pathways through the junctional complex or across the cells actively that participate in transport of ions, nutrients and other molecules could also be potential routes for drug delivery, which is discussed in detail in Section 3.1.”
- A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity (2020, background): “Calcium transporters (the Na+–Ca2+ exchanger) and voltage-gated K+ channel also regulate the ion transport across the BBB [107, 108].”
- Vascular Cognitive Impairment and Dementia (2019, background): “Conversely, in persons with AD pathology, there are well recognized decreases in perfusion, changes in the blood brain barrier, and alteration of the neurovascular unit including pericytes (11,51,68).”