Microglial heterogeneity after subarachnoid haemorrhage

Abstract

A specific type of haemorrhagic stroke called aneurysmal subarachnoid haemorrhage (SAH) affects people of working age and is more costly than other types of strokes. After SAH, people may look outwardly normal but experience a range of neurocognitive deficits 1 that affect their quality of life and ability to return to full productive work. SAH is caused by rupture of an aneurysm, which is a bulging structural abnormality of the wall of a cerebral artery in the subarachnoid space, on the brain surface. This results in an injection of blood into the subarachnoid space under arterial pressure with a number of pathological consequences, which may in turn affect clinical outcome. Immediate effects include mechanical injury and ischaemia (since increased intracranial pressure reduces cerebral perfusion within the rigid confines of the skull). Delayed effects include inflammation, the toxic effects of blood-derived products such as haemoglobin, vasospasm and hydrocephalus.Microglia are the brain's resident tissue macrophages, constituting circa 10% of the total cellular population. 2 They are derived from the yolk-sac and self-renew, 2 so are developmentally and functionally distinct from two other types of myeloid-lineage cells in the intracranial compartment, which are replenished continuously from the bloodstream: (1) CD163-positive perivascular, meningeal and choroid plexus macrophages and (2) monocytes in the cerebrospinal fluid -both of these two populationsThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

RU.521 mitigates subarachnoid hemorrhage-induced brain injury via regulating microglial polarization and neuroinflammation mediated by the cGAS/STING/NF-κB pathway

“…Morphologically, microglia in a state of homeostasis exhibit a highly ramified structure. However, when activated, microglia can assume polarized phenotypes, namely the classically-activated state (M1 phenotype) which is proinflammatory and marked by specific indicators such as CD16, CD86, and iNOS, or the alternatively-activated state (M2 phenotype) which is anti-inflammatory and marked by specific indicators such as CD206, CD163, and Arg-1 [15][16][17]. Previous studies have confirmed the extensive involvement of microglia in the occurrence and development of neuroinflammation in early brain injury [16].…”

Immunological Profile of Vasospasm after Subarachnoid Hemorrhage

“…Microglia include the resident immune cells of the central nervous system and can play a double-edged role in neuro-inflammation, which is associated with the functional outcome of SAH. The fact that microglia are able to self-renew makes them completely different from sibling myeloid-lineage cells such as meningeal macrophages and CSF monocytes [50].…”

“…M1 microglial cells predominate during the early stage of inflammation, playing a role in brain injury, while M2 microglia mostly appear in the late stage of inflammation, exerting a protective role [53]. More in detail, the expression of M1 markers such as interleukin-6 (IL-6), tumor necrosis factor (TNF) and Toll-like receptor 4 (TLR4) predominates during the first few days [54], while 5-10 days after the event, the up-regulation of IL-4 and transforming growth factor-beta (TGF-β) favors the transition to the M2-predominant phenotype [26,50].…”