期刊
ENDOCRINOLOGY
卷 163, 期 3, 页码 -出版社
ENDOCRINE SOC
DOI: 10.1210/endocr/bqac013
关键词
corticotropin-releasing factor (CRF); ischemic stroke; neuroinflammation; microglia
资金
- Hebei provincial government excellent personnel training project [303-08-03-02-0]
CRF plays a proinflammatory role in ischemic stroke by activating and transforming microglial cells through the TLR4/NF-kappa B signaling pathway, leading to aggravated neuronal injuries.
Ischemic stroke is the second leading cause of death worldwide. Therefore, exploring effective and emerging molecular targets for ischemic stroke is a primary 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, thus constructing 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 the TLR4/NF-kappa B signaling pathway. These effects can be blocked by antalarmin but not by astressin-2B. CRF significantly aggravated the neurological deficit, increased infarction volume, and exacerbated neuronal injuries. Additionally, CRF significantly improved the levels of TNF-alpha and phospho-NF-kappa B 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 provide evidence of the proinflammatory role of CRF in an ischemic stroke model and a possible underlying mechanism, which may facilitate the elucidation of potential treatment approaches for ischemic stroke.
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