Optimized dose of hydrogen-enriched water with minocycline combination therapy in experimental ischemic stroke.

Abstract

Using a transient middle cerebral artery occlusion (MCAO) rat model, this study investigated the dose-response relationship of hydrogen-enriched water (3.2 ppm) and assessed whether its combination with minocycline (20 mg/kg) enhances neuroprotection. Sixty-six male and female Sprague-Dawley rats underwent 60-minute MCAO and received hydrogen-enriched water at doses ranging from 5 to 30 mL/kg, alone or alongside minocycline, administered post-reperfusion and on days 1 and 2. At 7 days post-stroke, 20 mL/kg emerged as the optimal dose, yielding the best Garcia neurological scores and smallest infarct volumes, with a quadratic dose-response relationship (R = 0.751 for Garcia scores; R = 0.289 for lesion volume). The dual-agent regimen significantly surpassed hydrogen monotherapy in both functional recovery and infarct reduction, with no sex-based differences detected. These findings support dose-optimized hydrogen-enriched water as a neuroprotective strategy and highlight the additive benefit of combining it with minocycline.

Mechanism

Hydrogen-enriched water exerts anti-inflammatory and antioxidant effects, while minocycline provides additional neuroprotection; their combination appears to additively reduce infarct volume and improve neurological recovery following ischemia-reperfusion injury.