异常神经元兴奋促进缺血性脑卒中小鼠初级运动皮层的神经炎症，这一成果由山东大学王贞小组经过不懈努力而取得。该项研究成果发表在2025年3月12日出版的《中国药理学报》上。

在这项研究中，该团队研究了神经元活动和神经炎症之间的关系，在缺血模型主题的化学发生技术。建立小鼠MCAO脑缺血模型；体外氧-葡萄糖剥夺/再氧化（OGD/R）在PC12神经元中建立。通过测量c-Fos的表达，该团队发现MCAO引导M1初级运动皮层内兴奋性和抑制性神经元的激活，随后通过独特的神经元细胞外囊泡（EVs）的分泌诱导局部小胶质细胞的反应性激活。脑卒中皮质神经元异常神经元活动的化学发生抑制逆转了小胶质细胞的激活并减少了神经元凋亡。通过分析缺血M1皮层EVs中的miRNAs，该团队发现miR-128-3p在缺血神经元及其EVs中显著下调，导致神经元损伤和小胶质细胞的促炎极化。静脉注射miR-128-3p模拟显著提高神经元存活，减少神经炎症，并伴有更好的缺血性卒中后功能恢复。综上所述，卒中诱导的异常神经元活动降低了缺血神经元和ev中的miR-128-3p水平，导致卒中后小胶质细胞活化和神经元损伤增加。该研究强调，抑制异常神经元活动或递送mir -128-3p富集的ev是脑卒中治疗的新方法。

据介绍，目前缺血性卒中的治疗旨在通过静脉溶栓和/或血管内取栓实现快速再灌注，这已被证明可以减轻残疾。尽管再灌注治疗取得了重大进展，但功能恢复仍然不一致，主要是由于持续的神经元兴奋性毒性和神经炎症。

附：英文原文

Title: Aberrant neuronal excitation promotes neuroinflammation in the primary motor cortex of ischemic stroke mice

Author: Li, Ting-ting, Guo, Xiao-fan, Zhao, Yi-jing, Cheng, Ya-hong, Xin, Dan-qing, Song, Yan, Liu, De-xiang, Wang, Zhen

Issue&Volume: 2025-03-12

Abstract: Current treatments for ischemic stroke aim to achieve rapid reperfusion with intravenous thrombolysis and/or endovascular thrombectomy, which have proven to attenuate disability. Despite the significant progress in reperfusion therapies, functional recovery remains inconsistent, primarily due to ongoing neuronal excitotoxicity and neuroinflammation. In this study we investigated the relationship between neuronal activity and neuroinflammation in an ischemic mouse model using chemogenetic techniques. MCAO cerebral ischemia model was established in mice; in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) was established in PC12 neurons. By measuring c-Fos expression, we showed that MCAO caused the activation of both excitatory and inhibitory neurons within the M1 primary motor cortex, which subsequently induced reactive activation of local microglia through the secretion of unique neuronal extracellular vesicles (EVs). Chemogenetic inhibition of abnormal neuronal activity in stroke-affected cortical neurons reversed microglia activation and reduced neuronal apoptosis. By analyzing the miRNAs in EVs from the ischemic M1 cortex, we found that miR-128-3p was significantly downregulated in ischemia-challenged neurons and their EVs, leading to neuronal injury and proinflammatory polarization of microglia. Intravenous injection of miR-128-3p mimics significantly improved neuronal survival, reduced neuroinflammation accompanied by better functional recovery after ischemic stroke. In summary, stroke-induced abnormal neuronal activity reduces miR-128-3p levels in ischemic neurons and EVs, leading to increased microglia activation and neuronal injury after a stroke. The study highlights that inhibiting abnormal neuronal activity or delivering miR-128-3p-enriched EVs as novel methods for stroke treatment.

DOI: 10.1038/s41401-025-01518-6

Source: https://www.nature.com/articles/s41401-025-01518-6