Metformin and CoQ10 combination therapy: a novel approach to mitigating ischemia-reperfusion injury and cognitive impairment

BACKGROUND: Rapid reperfusion is critical in ischemic stroke management, but reperfusion injury often limits its therapeutic benefits. Metformin (MT) and Coenzyme Q10 (CQ) have shown individual neuroprotective effects in ischemic models, though their combined impact remains unexplored. This study investigates the effects of MT and CQ co-administration in a rat model of global cerebral ischemia. MATERIALS AND METHOD: The Wistar rats induced with brain injury after transient carotid artery ligation were pre-treated with vehicle, MT (200 mg/kg), CQ (200 mg/kg), or their combination for 21 days. The neurological deficit, cerebral infarction, and vascular permeability were assessed after 24 hours of reperfusion injury in rats. Cognitive changes were assessed using various behavioral observations. RESULTS: Vehicle-treated ischemia-reperfusion (IR) rats showed significant neurological deficits, larger infarct areas, vascular leakage, cognitive impairment, and increased apoptosis compared to the Sham group. MT and CQ monotherapies significantly reduced infarction and vascular permeability. Notably, the combination treatment demonstrated superior outcomes in minimizing infarct size, apoptosis, and cognitive decline. CONCLUSION: Co-administration of MT and CQ offered enhanced neuroprotection compared to individual treatments. This benefit may stem from additive or synergistic antioxidant effects and AMPK activation, suggesting potential for combined therapy in ischemic stroke management.