TY - JOUR
T1 - Dihydrolipoic acid enhances autophagy and alleviates neurological deficits after subarachnoid hemorrhage in rats
AU - Zhou, Keren
AU - Enkhjargal, Budbazar
AU - Mo, Jun
AU - Zhang, Tongyu
AU - Zhu, Qiquan
AU - Wu, Pei
AU - Reis, Cesar
AU - Tang, Jiping
AU - Zhang, John H.
AU - Zhang, Jianmin
N1 - Publisher Copyright:
© 2021
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - Autophagy
KW - Dihydrolipoic acid
KW - Early brain injury
KW - LAMP1
KW - Subarachnoid hemorrhage
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UR - http://www.scopus.com/inward/citedby.url?scp=85105590985&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2021.113752
DO - 10.1016/j.expneurol.2021.113752
M3 - Article
C2 - 33974879
SN - 0014-4886
VL - 342
JO - Experimental Neurology
JF - Experimental Neurology
M1 - 113752
ER -