Acute Post-Ischemic Neuroprotection By Metformin And Vitamin E: A Complementary Strategy Against Cerebral Ischemia-Reperfusion Injury

Abstract

Introduction:
Cerebral ischemia-reperfusion (IR) injury is a leading cause of long-term neurological disability, with limited post-stroke pharmacological options. Targeting energy metabolism and oxidative stress may offer complementary neuroprotection. This study evaluated the acute post-stroke efficacy of Metformin (MET) and Vitamin E (Vit-E), individually and in combination.

Materials and Methods:

Global cerebral ischemia was induced in male rats via bilateral common carotid artery occlusion (BCCAO) for 15 minutes followed by 3 days of reperfusion. Animals were divided into Sham, IR, MET (200 mg/kg, i.m.), Vit-E (100 mg/kg, i.m.), and MET + Vit-E groups. Treatments were administered once daily for 3 days post-IR. Behavioral performance, infarct size, oxidative stress markers (LPO, SOD, GSH), and BBB integrity (Evans Blue assay) were assessed.

Results:
MET and Vit-E, particularly in combination, significantly reduced infarct area, lipid peroxidation, and Evans Blue extravasation. The combination therapy showed enhanced antioxidant defense (SOD, GSH) compared to monotherapy. Behavioral tests showed cognitive improvement though it was not statistically significant during the 3-day treatment protocol.

Conclusion:
Post-stroke coadministration of MET and Vit-E confers complementary neuroprotection by targeting metabolic dysfunction and oxidative stress. These findings support a dual-mechanism strategy for managing cerebral IR injury and warrant further investigation with extended treatment durations.