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Microglial depletion impairs glial scar formation and aggravates inflammation partly by inhibiting STAT3 phosphorylation in astrocytes after spinal cord injury

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Neural Regeneration Research 2023年第6期18卷 1325-1331页

作者： Zhi-Lai Zhou Huan Xie Xiao-Bo Tian Hua-Li Xu Wei Li Shun Yao Hui Zhang The Spine Surgery Department Guangdong Second Provincial General HospitalGuangzhouGuangdong ProvinceChina The Second School of Clinical Medicine Southern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Anesthesiology ZhuJiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina

Astrocytes and microglia play an orchestrated role following spinal cord injury;however,the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully ***,microglia were pharmacologically depleted and the effects on the astrocytic response were *** further explored the potential mechanisms involving the signal transducers and activators of transcription 3(STAT3)*** in vivo experiments,we constructed a contusion spinal cord injury model in C57BL/6 *** deplete microglia,all mice were treated with colony-stimulating factor 1 receptor inhibitor PLX3397,starting 2 weeks prior to surgery until they were *** proliferation was examined by 5-ethynyl-2-deoxyuridine(EdU)and three pivotal inflammatory cytokines were detected by a specific Bio-Plex Pro^(TM) Reagent *** function,neuroinflammation,astrocyte activation and phosphorylated STAT3(pSTAT3,a maker of activation of STAT3 signaling)levels were *** in vitro experiments,a microglia and astrocyte coculture system was established,and the small molecule STA21,which blocks STAT3 activation,was applied to investigate whether STAT3 signaling is involved in mediating astrocyte proliferation induced by ***3397 administration disrupted glial scar formation,increased inflammatory spillover,induced diffuse tissue damage and impaired functional recovery after spinal cord *** depletion markedly reduced EdU+proliferating cells,especially proliferating astrocytes at 7 days after spinal cord *** sequencing analysis showed that the JAK/STAT3 pathway was downregulated in mice treated with *** immunofluorescence staining confirmed that PLX3397 significantly decreased STAT3 expression in ***,in vitro coculture of astrocytes and microglia showed that microglia-induced astrocyte proliferation was abolished by STA21 *** findings suggest that microglial depl

关键词： astrocytes coculture colony-stimulating factor 1 receptor inhibitor EdU glia scar inflammatory response microglia phosphorylation proliferation spinal cord injury STAT3

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