Mitochondrial Intercellular Transfer via Platelets After Physical Training Exerts Neuro-Glial Protection Against...

While thrombolytic therapy can be effective for stroke, many patients are unable to benefit due to time restrictions. In an aging society, sarcopenia, a condition marked by reduced muscle volume, often worsens recovery after stroke. Our study explored how mitochondria, which are abundant in muscle, could aid in stroke recovery through exercise-induced migration. Using mouse models of chronic hypoperfusion and ischemia, alongside in vitro studies with rat primary cells under oxygen-glucose deprivation and CoCl2 exposure, we found that treadmill exercise protected against white matter injury, myelin loss, astroglial formation, and memory deficits observed 28 days post-hypoperfusion. In acute ischemia models, training reduced glial activation and post-stroke complications. Exercise increased mitochondrial levels in muscle and blood, facilitating their migration between tissues via platelets. In vitro, the addition of muscle-derived mitochondria enhanced the survival of neurons, astrocytes, and oligodendrocytes. Notably, platelets carrying mitochondria from treadmill-trained mice significantly improved ischemic white matter injury and mitigated post-stroke complications. This study highlights mitochondria as a critical part of the secretome, suggesting that muscle-derived mitochondria might play a role in the protective effects of remote ischemic preconditioning. Cell-cell mitochondrial migration, therefore, could offer a promising new approach to reducing post-stroke complications and vascular dementia.