Dual microglia effects on blood brain barrier permeability induced by systemic inflammation
By Koichiro Haruwaka, Ako Ikegami, Y. Tachibana, N. Ohno, Hiroyuki Konishi, Akari Hashimoto, Mami Matsumoto, D. Kato, Riho Ono, H. Kiyama and 3 more. Nature Communications, 2019
798 citations recorded by the source corpus.
Microglia survey brain parenchyma, responding to injury and infections. Microglia also respond to systemic disease, but the role of blood–brain barrier (BBB) integrity in this process remains unclear. Using simultaneous in vivo imaging, we demonstrated that systemic inflammation induces CCR5-dependent migration of brain resident microglia to the cerebral vasculature. Vessel-associated microglia initially maintain BBB integrity via expression of the tight-junction protein Claudin-5 and make physical contact with endothelial cells. During sustained inflammation, microglia phagocytose astrocytic end-feet and impair BBB function. Our results show microglia play a dual role in maintaining BBB integrity with implications for elucidating how systemic immune-activation impacts neural functions. Although it is known that microglia respond to injury and systemic disease in the brain, it is unclear if they modulate blood–brain barrier (BBB) integrity, which is critical for regulating neuroinflammatory responses. Here authors demonstrate that microglia respond to inflammation by migrating towards and accumulating around cerebral vessels, where they initially maintain BBB integrity via expression of the tight-junction protein Claudin-5 before switching, during sustained inflammation, to phagocytically remove astrocytic end-feet resulting in impaired BBB function
Subfields: Immunology, Neurology
View Paper: https://www.semanticscholar.org/paper/c3f552b178950359c479d733c849b698185fc437
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Citations in the corpus
- The blood–brain barrier in systemic infection and inflammation (2021, background): “However, once inflammation was sustained, this initial protective response was followed by a transformation of the vessel-associated microglia to a CD68-positive phagocytic phenotype with loss of BBB integrity [100].”