Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Brain research institute, Zhejiang University, Hangzhou, Zhejiang, China; Collaborative Innovation Center for Brain Science, Zhejiang University, Hangzhou, Zhejiang, China; Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA.
Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA.
Exp Neurol. 2021 Aug;342:113752. doi: 10.1016/j.expneurol.2021.113752. Epub 2021 May 8.
Autophagy is a crucial pathological process in early brain injury (EBI) after subarachnoid hemorrhage (SAH). In this study, we investigated the role of dihydrolipoic acid (DHLA) on enhancing autophagy and alleviating neurological deficits after SAH. SAH was induced by endovascular perforation in male Sprague-Dawley rats. DHLA (30 mg/kg) was administered intraperitoneally 1 h (h) after SAH. Small interfering ribonucleic acid (siRNA) for lysosome-associated membrane protein-1 (LAMP1) was administered through intracerebroventricular (i.c.v) route 48 h before SAH induction. SAH grading score, neurological score, immunofluorescence staining, Fluoro-Jade C (FJC) staining, and Western blot were examined. DHLA treatment increased autophagy-related protein expression and downregulated the apoptosis-related protein expression 24 h after SAH. In addition, the DHLA treatment reduced neuronal cell death and alleviated neurological deficits after SAH. Furthermore, knockdown of LAMP1 abolished the neuroprotective effects of DHLA. These results indicate that LAMP1 may participate in autophagy after SAH. DHLA treatment can enhance autophagy, attenuate apoptosis, and alleviate neurofunctional deficits in EBI after SAH. It may provide an effective alternative method for the treatment of EBI after SAH.
自噬是蛛网膜下腔出血 (SAH) 后早期脑损伤 (EBI) 的一个关键病理过程。在这项研究中，我们研究了二氢硫辛酸 (DHLA) 在增强自噬和减轻 SAH 后神经功能缺损中的作用。通过血管内穿孔在雄性 Sprague-Dawley 大鼠中诱导 SAH。SAH 后 1 小时 (h) 通过腹腔内给予 DHLA (30mg/kg)。SAH 诱导前 48 小时通过侧脑室 (i.c.v) 途径给予溶酶体相关膜蛋白 1 (LAMP1) 的小干扰核糖核酸 (siRNA)。检查 SAH 分级评分、神经评分、免疫荧光染色、Fluoro-Jade C (FJC) 染色和 Western blot。DHLA 治疗可增加自噬相关蛋白的表达，并在 SAH 后 24 小时下调凋亡相关蛋白的表达。此外，DHLA 治疗可减少神经元细胞死亡并减轻 SAH 后的神经功能缺损。此外，LAMP1 的敲低消除了 DHLA 的神经保护作用。这些结果表明，LAMP1 可能参与 SAH 后的自噬。DHLA 治疗可增强自噬、减轻细胞凋亡并减轻 SAH 后 EBI 的神经功能缺损。它可能为 SAH 后 EBI 的治疗提供一种有效的替代方法。
