Objective:Stroke is one of the most common neurological disorders worldwide and is recognized as the second leading cause of death. This study aimed to investigate the combined effect of aerobic exercise and adenosine injection on the expression of the HIF-1α gene in the brain of Wistar rats following cerebral ischemia. Materials and Methods:Fifty adult male Wistar rats (8–10 weeks old, weighing 240–270 g) were randomly assigned to five groups: Sham, Ischemia+Control, Ischemia+Exercise, Ischemia+Adenosine, and Ischemia+Adenosine+Exercise. After induction of cerebral ischemia, rats in the exercise groups followed a treadmill protocol five days per week, starting at 20 m/min with no incline for 18 minutes in the first week, gradually increasing to 30 m/min at a 10° incline for 50 minutes by the eighth week. Adenosine (0.3 mg/kg) was administered once daily to the relevant treatment groups. Forty-eight hours after completing the exercise protocol, the rats were sacrificed, and brain tissue was collected for analysis of HIF-1α gene expression using PCR. Data were analyzed using one-way ANOVA followed by Bonferroni post hoc test. Results:HIF-1α gene expression was significantly elevated in the Ischemia+Adenosine+Exercise, Ischemia+Exercise, and Ischemia+Adenosine groups, with the highest increase observed in the combined treatment group. These changes were statistically significant compared to both the Sham (P<0.001) and Ischemia+Control (P<0.001) groups.

Conclusion:The combination of aerobic exercise and adenosine enhances HIF-1α expression by simultaneously activating energy-producing and cellular signaling pathways, thereby promoting neuronal survival under ischemic conditions. This biological synergy offers promising potential for developing targeted therapeutic and rehabilitation protocols for stroke patients.