Mitochondrial Intercellular Transfer via Platelets After Physical Training Exerts Neuro‐Glial Protection Against Cerebral Ischemia

TL;DR

Exercise promotes muscle mitochondria transfer via platelets, which protects the brain against stroke and dementia.

Contribution

Discovery that muscle-derived mitochondria, transferred via platelets after exercise, protect neurons and glial cells in stroke.

Findings

Treadmill exercise reduces white matter injury and glial activation after cerebral ischemia.

Muscle-derived mitochondria transferred via platelets enhance survival of neurons and astrocytes in vitro.

Platelet transfusion from trained mice mitigates post-stroke complications and white matter injury.

Abstract

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.

Treadmill training protects against white matter injury and reduces cerebral infarction.

Muscle‐derived mitochondrial transfer via platelets is promoted by treadmill training.

Platelet transfusion emerges as a potential low‐risk therapeutic strategy for sequelae and vascular dementia.

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