Low-dose Esketamine promotes brain protection via the ERK/Nrf2 pathway in vascular dementia rats

Abstract

Backdround : By establishing the rat model of vascular dementia and observing the effects of low-dose Esketamine on cognitive function and related mechanisms in rats with vascular dementia, providing a new idea for clinical drug treatment of Vascular dementia (VD). Methods 100 rats were randomly divided into five groups: sham operation group, vascular dementia group, Esketamine group, Esketamine + PD98059 group, and Esketamine + DMSO group. Except for the sham operation group, the other groups were established vascular dementia rat models by intraperitoneal injection of sodium nitroprusside to reduce blood pressure and bilateral common carotid artery occlusion/reperfusion. The Morris water maze test assessed rats' learning and memory ability. ELISA detected changes in SOD and IL-1β levels in rat serum; the levels of ERK, Nrf2, and p-ERK in the hippocampus were detected by western blotting; and the pathological changes in the hippocampus of rats in each group were detected by HE staining. Results The results showed that the escape latency of VD rats was significantly higher than that of Group Sham and Group VK. In contrast, the times of crossing the platform and the staying time distance of the target quadrant of VD rats were significantly lower than that of Group Sham and Group VK. Compared with the Group VD, the expression of ERK, p-ERK and Nrf2 in the hippocampus of Group VK increased, which improved brain injury, increased the level of serum antioxidant SOD and decreased the level of inflammatory factor IL-1β. Conclusion Low-dose ketamine can improve cognitive impairment and reduce the damage to the hippocampus in VD rats. Its protective effect is related to increasing BDNF levels, activating the ERK/Nrf2 pathway, increasing antioxidant substances in the body and inhibiting inflammatory factors.