The blood-brain barrier.
In autoimmune neurologic disorders, the blood-brain barrier (BBB) plays a central role in immunopathogenesis, since this vascular interface is an entry path for cells and effector molecules of the peripheral immune system to reach the target organ, the central nervous system (CNS). The BBB's unique anatomic structure and the tightly regulated interplay of its cellular and acellular components allow for maintenance of brain homeostasis, regulation of influx and efflux, and protection from harm; these ensure an optimal environment for the neuronal network to function properly. In both health and disease, the BBB acts as mediator between the periphery and the CNS. For example, immune cell trafficking through the cerebral vasculature is essential to clear microbes or cell debris from neural tissues, while poorly regulated cellular transmigration can underlie or worsen CNS pathology. In this chapter, we focus on the specialized multicellular structure and function of the BBB/neurovascular unit and discuss how BBB breakdown can precede or be a consequence of neuroinflammation. We introduce the blood-cerebrospinal fluid barrier and include a brief aside about evolutionary aspects of barrier formation and refinements. Lastly, since restoration of barrier function is considered key to ameliorate neurologic disease, we speculate about new therapeutic avenues to repair a damaged BBB.
Neuro/Immuno Discovery Biology, Biogen, Cambridge, MA, USA. Electronic address: birgit.obermeier@biogen.com.
Birgit
B
Obermeier
Biomarkers and Experimental Medicine, Biogen, Cambridge, MA, USA.
Ajay
A
Verma
Neuro/Immuno Discovery Biology, Biogen, Cambridge, MA, USA.
Richard M
RM
Ransohoff
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000033:anatomy & histology / Q000502:physiology*; D002555:Cerebrospinal Fluid / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology
BBB breakdown; BBB evolution; BBB repair; blood–brain barrier; blood–cerebrospinal fluid barrier; neuroinflammation; neurovascular unit