Microglial polarization:
Microglial polarization appears to play a significant part in the pathogenic processes of neuroinflammation following subarachnoid hemorrhage, according to increasing data (Gao et al., 2021). Microglia responds quickly to a variety of brain injuries by modifying the shape and polarization of their cytoplasmic structures. After a SAH, neuroinflammation develops over time and plays a role in both EBI and the long-term decline in cognitive function. As resident immune cells, microglia coordinates neuroinflammation differently in neurological disorders with varying degrees of polarization (Zheng, Lyu, Lam, Lam, Poon & Wong, 2020). After SAH, activated microglia are thought to polarize into two phenotypes: classic M1 (pro-inflammatory) and alternative M2 (anti-inflammatory), depending on the stimulus (Li & Barres, 2018). Lipopolysaccharide (LPS) and the pro-inflammatory cytokine interferon-γ (IFN-γ) traditionally stimulate microglia to the M1 phenotype through the release of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-6 and When microglia are stimulated by IL-4 or IL-13, they adopt an alternative M2 phenotype and express anti-inflammatory molecules such as transforming growth factor beta and IL-10 (Zheng, Lyu, Lam, Lam, Poon & Wong, 2020). According to (Liu et al., 2020), Hb-induced microglial pro-inflammatory polarization was inhibited more effectively by the RvD1-ALX/FPR2 connection, potentially by negatively modulating the signaling activities of IRAK1/TRAF6/NF-κB or MAPKs. Similarly, (You et al., 2016) indicated that, Rapamycin and AZD8055 may promote a selective modification of microglia polarization to the M2 phenotype for SAH therapy by inhibiting the mTOR pathway. RhMFG-E8 treatment reduces the microglial inflammatory response, which is linked to the M2 microglial shift and may have direct neuroprotective effects, and it may include the integrin 3/SOCS3/STAT3 signaling pathway (Gao et al., 2021). (Wei et al., 2017) study, showed that Erythropoietin reduces EBI after SAH by regulating microglia polarization through the EPOR/JAK2-STAT3 pathway. The above facts suggest that, modulating M1 and M2 microglial polarization could be a promising neuroprotective strategy. Further studies are needed to better understand the application of microglial modulation in SAH.