Baihui-Penetrating-Qubin Acupuncture Attenuates Neurological Deficits Through SIRT1/FOXO1 Reducing Oxidative Stress and Neuronal Apoptosis in Intracerebral Hemorrhage Rats

Abstract

Background

Intracerebral hemorrhage (ICH) is a significant global disease with high mortality and disability. As of now, there is no effective therapy available. Oxidative stress and neuronal apoptosis play essential roles in ICH, determining neuronal survival. In our preliminary studies, we found that Baihui-penetrating-Qubin acupuncture could improve neurological deficits and neuropathological damage in the perihematomal area in ICH rats. The SIRT1/FOXO1 signaling pathway has been reported to mediate antioxidant and anti-neuronal apoptosis. This study aimed to investigate the effects of Baihui-penetrating-Qubin acupuncture on oxidative stress and neuronal apoptosis after ICH and the role of SIRT1/FOXO1 in acupuncture's neuroprotection.

Methods

ICH rat models were established by autologous tail blood (50 µL) infusion into the caudate nucleus. EX527, SIRT1-specific inhibitor was intraperitoneally administered 3 days before ICH. Baihui-penetrating-Qubin acupuncture treatment was performed once a day for 30 min after ICH. Neurological deficits were evaluated using the modified neurological severity score (mNSS). Brain edema was evaluated using brain water content. HE staining and Nissl staining were used to evaluate neuropathological damage in the perihematomal area. Terminal deoxynucleotidyl transferase dUTP nick end labeling was used to quantify neuronal apoptosis. Specific kits were used to detect the levels of SOD, CAT, GSH-Px in the brain. The oxidative DNA damage was evaluated using enzyme-linked immunosorbent assay to detect the level of 8-hydroxyguanosine (8-OHdG). Western blot was used to evaluate the expressions of SIRT1, Ac-FOXO1, FOXO1, Bcl-2, and Bax. Immunofluorescence staining was conducted to detect the cellular localization of SIRT1.

Results

Baihui-penetrating-Qubin acupuncture improved the neurological deficits and brain edema, reduced the pathological injury and neuronal degeneration in 3 days in the perihematomal area after ICH. Mechanistically, acupuncture reduced oxidative stress injury and neuronal apoptosis via activating SIRT1/FOXO1 pathway. The neuroprotective effects of acupuncture were abolished by injection of the SIRT1 inhibitor EX527.

Conclusions

Baihui-penetrating-Qubin acupuncture could reduce oxidative stress and neuronal apoptosis, at least in part, through the SIRT1/FOXO1 signaling pathway, improving neurological deficits and neuropathological damage after ICH. These findings suggest that Baihui-penetrating-Qubin acupuncture is an effective therapy for ICH, as well as targeting SIRT1 signaling to promote neuron survival could be a potential therapeutic strategy.