Corticotropin-releasing factor aggravates ischemic stroke injury by the inflammatory activation of microglia

Endocrinology. 2022 Feb 5:bqac013. doi: 10.1210/endocr/bqac013. Online ahead of print.ABSTRACTIschemic stroke is the second leading cause of death worldwide. Therefore, exploring effective and emerging molecular targets for ischemic stroke is the main task of basic and clinical research. The aim of the present study was to investigate the function of corticotropin-releasing factor (CRF) in ischemic stroke and its related mechanisms, to provide a reference for the treatment of ischemic stroke. CRF, antalarmin or astressin-2B were used to activate or block the CRF1 (CRF receptor 1) or CRF2 (CRF receptor 2) in BV2 cells and adult male mice which constructed a distal middle cerebral artery occlusion (dMCAO) model. CRF not only accelerated microglial activity by promoting transcription and production of inflammatory factors, but also promoted the transformation of activated BV2 cells from a neuroprotective phenotype (M2) to cytotoxic phenotype (M1), and these effects were mediated by TLR4/NF-κB signaling pathway. The effects above can be blocked by antalarmin, but not by astressin-2B. CRF significantly aggravate the neurological deficit, increased infarction volume, and exacerbated neuronal injuries. Additionally, CRF significantly improved the levels of TNF-α and phospho-NF-κB in the ischemia penumbra. Finally, CRF significantly increased the number of CD16/Iba-1 -positive cells and decreased the number of CD206/Iba-1-positive cells in the ischemia penumbra. These results prov...
Source: Endocrinology - Category: Endocrinology Authors: Source Type: research