文献检索，用中文搜 PubMed

BACKGROUND

Gut dysmotility is common after ischemic stroke, but the mechanism underlying this response is unknown. Under homeostasis, gut motility is regulated by the neurons of the enteric nervous system that control contractile/relaxation activity of muscle cells in the gut wall. More recently, studies of gut inflammation revealed interactions of macrophages with enteric neurons are also involved in modulating gut motility. However, whether poststroke gut dysmotility is mediated by direct signaling to the enteric nervous system or indirectly via inflammatory macrophages is unknown.

METHODS AND RESULTS

We examined these hypotheses by using a clinically relevant permanent intraluminal midcerebral artery occlusion experimental model of stroke. At 24 hours after stroke, we performed in vivo and ex vivo gut motility assays, flow cytometry, immunofluorescence, and transcriptomic analysis. Stroke-induced gut dysmotility was associated with recruitment of muscularis macrophages into the gastrointestinal tract and redistribution of muscularis macrophages away from myenteric ganglia. The permanent intraluminal midcerebral artery occlusion model caused changes in gene expression in muscularis macrophages consistent with an altered phenotype. While the size of myenteric ganglia after stroke was not altered, myenteric neurons from post-permanent intraluminal midcerebral artery occlusion mice showed a reduction in neuronal nitric oxide synthase expression, and this response was associated with enhanced intestinal smooth muscle contraction ex vivo. Finally, chemical sympathectomy with 6-hydroxydopamine prevented the loss of myenteric neuronal nitric oxide synthase expression and stroke-induced slowed gut transit.

CONCLUSIONS

Our findings demonstrate that activation of the sympathetic nervous system after stroke is associated with reduced neuronal nitric oxide synthase expression in myenteric neurons, resulting in impaired smooth muscle relaxation and dysregulation of gut transit.

BACKGROUND

METHODS AND RESULTS

CONCLUSIONS

背景

肠道运动功能障碍在缺血性中风后很常见，但其潜在机制尚不清楚。在稳态下，肠道运动由肠神经系统的神经元调节，这些神经元控制肠壁肌肉细胞的收缩/舒张活动。最近，肠道炎症研究表明，巨噬细胞与肠神经元的相互作用也参与调节肠道运动。然而，中风后肠道运动功能障碍是通过直接向肠神经系统发出信号介导的，还是通过炎症巨噬细胞间接介导的，目前尚不清楚。

方法和结果

我们使用临床上相关的永久性大脑中动脉腔内闭塞性中风实验模型来检验这些假设。中风后24小时，我们进行了体内和体外肠道运动测定、流式细胞术、免疫荧光和转录组分析。中风诱导的肠道运动功能障碍与肌层巨噬细胞募集到胃肠道以及肌层巨噬细胞从肌间神经节重新分布有关。永久性大脑中动脉腔内闭塞模型导致肌层巨噬细胞基因表达发生变化，与表型改变一致。虽然中风后肌间神经节的大小没有改变，但永久性大脑中动脉腔内闭塞小鼠的肌间神经元显示神经元型一氧化氮合酶表达减少，并且这种反应与体外肠道平滑肌收缩增强有关。最后，用6-羟基多巴胺进行化学交感神经切除术可防止肌间神经元型一氧化氮合酶表达的丧失和中风诱导的肠道运输减慢。