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Intracerebroventricular BDNF infusion may reduce cerebral ischemia/reperfusion injury by promoting autophagy and suppressing apoptosis
Journal of Cellular and Molecular Medicine ( IF 5.3 ) Pub Date : 2024-03-23 , DOI: 10.1111/jcmm.18246
Umit Yilmaz 1 , Kevser Tanbek 2 , Semir Gul 3 , Ahmet Koc 4 , Mehmet Gul 3 , Suleyman Sandal 2
Affiliation  

Here, it was aimed to investigate the effects of intracerebroventricular (ICV) Brain Derived Neurotrophic Factor (BDNF) infusion for 7 days following cerebral ischemia (CI) on autophagy in neurons in the penumbra. Focal CI was created by the occlusion of the right middle cerebral artery. A total of 60 rats were used and divided into 4 groups as Control, Sham CI, CI and CI + BDNF. During the 7‐day reperfusion period, aCSF (vehicle) was infused to Sham CI and CI groups, and BDNF infusion was administered to the CI + BDNF group via an osmotic minipump. By the end of the 7th day of reperfusion, Beclin‐1, LC3, p62 and cleaved caspase‐3 protein levels in the penumbra area were evaluated using Western blot and immunofluorescence. BDNF treatment for 7 days reduced the infarct area after CI, induced the autophagic proteins Beclin‐1, LC3 and p62 and suppressed the apoptotic protein cleaved caspase‐3. Furthermore, rotarod and adhesive removal test times of BDNF treatment started to improve from the 4th day, and the neurological deficit score from the 5th day. ICV BDNF treatment following CI reduced the infarct area by inducing autophagic proteins Beclin‐1, LC3 and p62 and inhibiting the apoptotic caspase‐3 protein while its beneficial effects were apparent in neurological tests from the 4th day.

中文翻译:

脑室内注射 BDNF 可通过促进自噬和抑制细胞凋亡来减轻脑缺血/再灌注损伤

本研究的目的是研究脑缺血 (CI) 后脑室内 (ICV) 脑源性神经营养因子 (BDNF) 输注 7 天对半暗带神经元自噬的影响。局灶性 CI 是由右侧大脑中动脉闭塞造成的。总共使用60只大鼠并分为4组:对照组、假手术CI组、CI组和CI+BDNF组。在7天的再灌注期间,Sham CI和CI组输入aCSF(载体),CI + BDNF组通过微型渗透泵输入BDNF。再灌注第 7 天结束时,使用蛋白质印迹和免疫荧光评估半暗带区域的 Beclin-1、LC3、p62 和 cleaved caspase-3 蛋白水平。 BDNF 治疗 7 天可减少 CI 后的梗死面积,诱导自噬蛋白 Beclin-1、LC3 和 p62,并抑制凋亡蛋白 cleaved caspase-3。此外,BDNF治疗的转棒和粘合剂去除测试时间从第4天开始改善,神经功能缺损评分从第5天开始改善。 CI 后的 ICV BDNF 治疗通过诱导自噬蛋白 Beclin-1、LC3 和 p62 并抑制凋亡 caspase-3 蛋白来减少梗塞面积,同时从第 4 天起在神经系统测试中其有益效果就很明显。
更新日期:2024-03-23
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