Effect Of AMPK Activator-AICAR On Transient Cerebral Ischemia-reperfusion In Aged Mice

Objective Transient cerebral ischemia occurred during anesthesia and surgery and subsequent reperfusion injury to brain function is one of the hot spots in recent years in the field of anesthesia. Aging is an independent risk factor of ischemic cerebrovascular disease. Adenosine monophosphate-activated protein kinase(AMP-activated protein kinase, AMPK) can be activated in many conditions, such as lack of energy, ischemia and hypoxia. AMPK was praised as "the regulation of cellular energy device" and can regulate the energy metabolism through a series of reactions. Cerebral ischemia-reperfusion injury associated with cellular energy metabolism. Studies have found that AMPK was insufficient activated in aged mice after cerebral ischemia compared with young mice, and aged mice suffered from severe brain ischemia-reperfusion injury. In this experiment, we investigate the effect of AMP-activated protein kinase(AMPK) activator AICAR on transient cerebral ischemia-reperfusion in aged mice.Methods Sixty aged 18-20 months male C57BL/6 mice were divided into three groups(n=20):sham group(group S), cerebral ischemia-reperfusion group(group I/R), cerebral ischemia-reperfusion group+AICAR(group I/R+AICAR). In group group I/R and group I/R+AICAR, bilateral common carotid artery were occluded for 10 minutes to establish transient cerebral ischemia model. AICAR was injected intraperitoneally at 500 mg/kg before occluding artery in group I/R+AICAR. The same volume of saline was injected intraperitoneally in group S and group I/R. The NBS of all the mice were evaluated at the 72 h after reperfusion. Then all mice were sacrificed and their brain were immediately harvested. Hippocampal CAl region was dissected for microscopic examination(by HE), detection of neuronal apoptosis rate(by TUNEL) and expression of p-AMPKα,caspase-3 and Bax(by Western blot).Results Compared with group S, the NBS, the neuronal apoptosis rate and the expression of protein p-AMPKα, caspase-3and Bax were significantly increased in group I/R and group I/R+AICAR(P<0.05). Compared with group I/R, the expression of protein p-AMPKαwas up-regulated(P<0.05) and the NBS, the neuronal apoptosis rate and the expression of protein caspase-3, Bax were significantly decreased in group I/R+AICAR(P<0.05). The level of AMPKα2 mRNA were no significant differences in the three groups(P<0.05).Conclusion The experimental results showed that compared with group I/R, the expression of protein p-AMPKαwas up-regulated and the NBS, the neuronal apoptosis rate and the expression of protein caspase-3, Bax were significantly decreased in group I/R+AICAR. This suggests that AMPK activator AICAR can significantly improve the neurological function and reduce the degree of apoptosis in hippocampal neurons. It indicated that AMPK activator AICAR can up-regulate the expression levels of p-AMPKα in hippocampus and reduce neuronal apoptosis in aged mice. This may be because, AMPK was insufficient activated in aged mice after cerebral ischemia compared with young mice, and aged mice suffered from severe brain ischemia-reperfusion injury. Giving AMPK activator AICAR in advance can compensate for this deficiency and play a protective role in the brain. This provides a new direction and target for ischemic cerebrovascular disease prevention and treatment, but the exact mechanism and how to control the intensity of activation remains to be further studied.