Neuroprotective Effect of the Combination of Aerobic Exercise and Adenosine on the A2A Receptor Gene Expression and Complications of Cerebral Stroke in the Hippocampus of adult Male Rat

Stroke is a neurological disorder and the second leading cause of death worldwide. Recently, studies on neuroprotective treatments for stroke have become a hot topic globally. The present study aimed to investigate the neuroprotective effect of a combination of aerobic exercise and adenosine on the expression of the A2a gene and the consequences of stroke injury in the hippocampus of male rats. Fifty male Wistar rats (8-10 weeks old, weighing 240-270 grams) were randomly divided into five groups: (sham, control+ischemia, ischemia+exercise, ischemia+adenosine, and ischemia+adenosine+exercise). After inducing ischemia, rats in exercise groups performed treadmill running 5 days per week for 8 week. Adenosine simultaneously once per day to Adenosine-treated groups were injected. 48 hours after completing the exercise protocol, hippocampal tissue was collected for cell death, and measuring of the A2a expression using the RT- PCR method. The data were analyzed using Anova and post hoc Bonferroni’s test. The number of dead cells increased in the ischemia group compared to the sham and decreased in the ischemia+adenosine+Exercise and ischemia+exercise groups compared to the ischemia group. The A2a expression in group ischemia+adenosine+exercise, ischemia+exercise, and ischemia+adenosine showed respectively the highest increase, with a significant difference compared to the sham (P<0/001) and control+ischemia (P<0/001) groups. aerobic exercise and adenosine, both independently and interactively, can serve as a neuroprotective combination by increasing the expression of the A2a and stimulating the signaling and mechanisms related to the reduction of cell death, providing therapeutic and protective effects against ischemic stroke-induced consequences.