Abstract Body: Background: Despite the effectiveness of immediate treatment, such as thrombolytic therapy, after a stroke, many patients are unable to benefit due to time restrictions. In an aging society, sarcopenia, a condition characterized by reduced muscle volume, is emerging as a significant issue, often contributing to poor recovery after stroke. Our study examined the role of mitochondria, which are abundant in muscle, and their migration during exercise in the context of stroke recovery.
Methods: We used mice models to simulate chronic hypoperfusion and distal middle cerebral artery occlusion. We also conducted in vitro studies with rat primary cells, co-cultured with a nonlethal concentration of CoCl₂ and oxygen-glucose deprivation.
Results: We found that 28 days post-hypoperfusion, there was a progression in white matter injury, including myelin loss, astroglial formation, and memory disorder. However, treadmill training protected against these damages. In cases of acute ischemia, training improved complications and reduced glial activation. We observed increased mitochondria in muscle and blood due to training, which migrated between tissues using platelets. In vitro analysis revealed that adding muscle mitochondria improved the survival of neurons, astrocytes, and oligodendrocytes. Most importantly, we found that mitochondrial transfusion from treadmill-trained mice platelet improved ischemic white matter injury and post-stroke complications.
Conclusions: The study showed mitochondria as part of the secretome, essential for regulating cell interactions. It explored mitochondrial secretion, transfer between cells, and dynamics influencing ischemic tissue. The protective effects of remote ischemic preconditioning might be linked to muscle-derived mitochondria, a recent phenomenon. Unlike conventional platelet transfusion, mitochondria administration even from cryopreserved platelets shows brain protection effect. Therefore, this suggests that the advantage of this therapy is that mitochondria can be extracted from platelets that could not be used for transfusion and used for treatment. Our study suggests it could be a promising new treatment for reducing post-stroke complications and vascular dementia.