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      Blood-Brain Barrier: From Physiology to Disease and Back

      1 , 1 , 1 , 1 , 1
      Physiological Reviews
      American Physiological Society

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          Abstract

          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.

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          Author and article information

          Journal
          Physiological Reviews
          Physiological Reviews
          American Physiological Society
          0031-9333
          1522-1210
          January 2019
          January 2019
          : 99
          : 1
          : 21-78
          Affiliations
          [1 ]Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California; and Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, California
          Article
          10.1152/physrev.00050.2017
          6335099
          30280653
          9d78e2a0-3cbd-44b3-8034-207970eb0e26
          © 2019
          History

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