Explore the molecular mechanism of controlled hypothermic surgery to promote autophagy and inhibit oxidative damage to reduce the damage of neurovascular unit barrier

Abstract

Background: Controlled hypothermia surgery is a method to lower the body temperature to a certain level in order to reduce the body’s metabolism and maintain or delay cell activity. Autophagy can antagonize the apoptotic effect of cells by promoting cell survival.

Methods: Normal and hypothermic cerebral ischemia models in mice were established. Nissl staining and HE staining were used to analyze the pathological damage characteristics of mouse brain tissue. Microplate reader was used to measure the activity of SOD, and the fluorescent probe DCFH-DA was used to detect the content of ROS. The brain tissue sections were stained with MDC to observe the characteristics of autophagy. The characteristics of autophagosomes were observed by TEM. Western blot analysis was used to determine the expression of related proteins in brain tissue. RT-PCR analysis was used to determine the mRNA expression of genes Bcl-2 and Bax in brain tissue.

Results: HE staining and Nissl staining indicated that controlled hypothermia effectively reduced pathological damage. The activity of SOD and the content of ROS indicated that LI group has the lowest degree of oxidative damage. MDC staining, TEM imaging and Western blot analysis showed that controlled hypothermia surgery also increased the content of autophagosomes, and then promoted autophagy and apoptosis. RT-PCR also showed that LI group has the highest Bax/Bcl-2 ratio.

Conclusion: Controlled hypothermia can protect brain tissue and reduces damage caused by cerebral ischemia by promoting cell autophagy.