脑缺血再灌注损伤（CIRI）通常会在中风患者接受再灌注治疗后导致有害的并发症。据报道，运动预适应（EP）可以促进大脑功能恢复。我们旨在探讨CIRI中EP的具体机制。将Sprague-Dawley大鼠随机分为Sham组、大脑中动脉闭塞组（MCAO）和EP组（n = 11）。 EP组大鼠接受为期3天的适应性训练（10m/min，20min/天，0°倾斜）和正式训练3周（6天/周，25m/min，30min/天） ，倾斜度为 0°）。然后对大鼠进行MCAO手术建立CIRI模型。 48小时后，测量大鼠的神经功能缺损和脑梗塞。检测到大脑皮质中的神经元死亡和细胞凋亡。此外，通过RNA测序探讨EP对CIRI的具体作用机制，并进一步应用qPCR和Western blotting验证RNA测序结果。EP改善MCAO大鼠的神经功能缺损评分并减少脑梗塞。此外，缺血前运动还可以减轻 MCAO 大鼠的神经元死亡和大脑皮质细胞凋亡。重要的是，通过RNA测序鉴定出17个差异表达基因（DEG），这些DEG主要富集在HIF-1通路、细胞衰老、癌症中的蛋白聚糖等方面。 qPCR和Western blotting进一步证实EP可抑制MCAO大鼠TIMP1、SOCS3、ANGPTL4、CDO1和SERPINE1的表达。EP可改善体内CIRI，其机制可能与TIMP1表达和HIF-1通路有关，这为MCAO大鼠的CIRI改善提供了新的靶点。 CIRI 治疗。© 2024 作者。 《大脑与行为》由 Wiley periodicals LLC 出版。

Cerebral ischemia reperfusion injury (CIRI) often leads to deleterious complications after stroke patients receive reperfusion therapy. Exercise preconditioning (EP) has been reported to facilitate brain function recovery. We aim to explore the specific mechanism of EP in CIRI.Sprague-Dawley rats were randomized into Sham, middle cerebral artery occlusion (MCAO), and EP groups (n = 11). The rats in the EP group received adaptive training for 3 days (10 m/min, 20 min/day, with a 0° incline) and formal training for 3 weeks (6 days/week, 25 m/min, 30 min/day, with a 0° incline). Then, rats underwent MCAO surgery to establish CIRI models. After 48 h, neurological deficits and cerebral infarction of the rats were measured. Neuronal death and apoptosis in the cerebral cortices were detected. Furthermore, RNA sequencing was conducted to investigate the specific mechanism of EP on CIRI, and qPCR and Western blotting were further applied to confirm RNA sequencing results.EP improved neurological deficit scores and reduced cerebral infarction in MCAO rats. Additionally, pre-ischemic exercise also alleviated neuronal death and apoptosis of the cerebral cortices in MCAO rats. Importantly, 17 differentially expressed genes (DEGs) were identified through RNA sequencing, and these DEGs were mainly enriched in the HIF-1 pathway, cellular senescence, proteoglycans in cancer, and so on. qPCR and Western blotting further confirmed that EP could suppress TIMP1, SOCS3, ANGPTL4, CDO1, and SERPINE1 expressions in MCAO rats.EP can improve CIRI in vivo, the mechanism may relate to TIMP1 expression and HIF-1 pathway, which provided novel targets for CIRI treatment.© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.