Dual microglia effects on blood brain barrier permeability induced by systemic inflammation.
Koichiro HaruwakaAko IkegamiYoshihisa TachibanaNobuhiko OhnoHiroyuki KonishiAkari HashimotoMami MatsumotoDaisuke KatoRiho OnoHiroshi KiyamaAndrew J MoorhouseJunichi NabekuraHiroaki WakePublished in: Nature communications (2019)
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.
Keyphrases
- blood brain barrier
- cerebral ischemia
- inflammatory response
- neuropathic pain
- endothelial cells
- spinal cord injury
- oxidative stress
- high resolution
- physical activity
- resting state
- mental health
- white matter
- multiple sclerosis
- functional connectivity
- cross sectional
- immune response
- binding protein
- photodynamic therapy
- small molecule
- regulatory t cells
- protein protein
- drug induced