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.Copyright © 2021. Published by Elsevier Inc.
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Keren Zhou,Budbazar Enkhjargal,Jun Mo,Tongyu Zhang,Qiquan Zhu,Pei Wu,Cesar Reis,Jiping Tang,John H Zhang,Jianmin Zhang
John H Zhang