Activation of Cholinergic Anti-Inflammatory Pathway Ameliorates Cerebral and Cardiac Dysfunction After Intracerebral Hemorrhage Through Autophagy

• DOI: 10.3389/fimmu.2022.870174
• Publication Date: 2022-06-23T09:20:59Z
• Authors: Yue Su; Wei Zhang; Ruoxi Zhang; Quan Yuan; Ruixia Wu; Xiaoxuan Liu; Jimusi Wuri; Ran Li; Tao Yan
• Keywords: Cerebral edema; Proinflammatory cytokine

Intracerebral hemorrhage (ICH) is the devastating subtype of stroke with cardiovascular complications, resulting in high rates mortality and morbidity release inflammatory factors. Previous studies have demonstrated that activation α7nAChR can reduce immune inflammation-related diseases by triggering cholinergic anti-inflammatory pathway (CAIP). mediates protection from nervous system inflammation through AMPK-mTOR-p70S6K-associated autophagy. Therefore, purpose this study to explore whether improves cerebral cardiac dysfunction after ICH autophagy.Male C57BL/6 mice were randomly divided into five groups (1): Control + saline (2), ICH+ (3), PNU-282987 (4), MLA (5), 3-MA. The neurological function was evaluated at multiple time points. Brain water content measured 3 days assess severity brain edema. PCR, immunofluorescence staining, Western Blot performed 7 detect Picro-Sirius Red staining 30 evaluate myocardial fibrosis, echocardiography measure function.Our results indicated reduced factors (MCP-1, IL-1β, MMP-9, TNF-α, HMGB1, TLR2), promoted polarization macrophage/microglia subtypes(CD206), repaired blood-brain barrier injury (ZO-1, Claudin-5, Occludin), alleviated acute edema then recovered dysfunction. Echocardiography PSR ameliorated showed increased autophagy protein (LC3, Beclin) decreased P62. It promotes recovers heart ICH.In conclusion, functional outcomes activated α7nAChR, which may be attributable promoting reducing reactions ICH.