Mitochonic acid 5, an ATP production accelerator, protects against neurological damage in ischemic stroke

Cerebral infarction is a severe condition that causes motor dysfunction and disorientation due to irreversible neuronal cell death. After an ischemic stroke, the lack of oxygen and nutrients induces cerebral neuronal damage along with mitochondrial dysfunction. Therefore, activating mitochondrial function is a promising strategy for treating ischemic stroke. This study aimed to examine whether Mitochonic acid 5 (MA-5), a compound that targets mitochondria to stimulate ATP synthesis, has protective effects against cerebral ischemia/reperfusion (I/R) injury. We first confirmed that MA-5 significantly increases ATP production after 1 h of exposure to neuron-like cells. MA-5 also increased ATP production coupled respiration in SH-SY5Y cells after the induction of OGD/R. After inducing cerebral I/R in mice via transient midbrain occlusion (t-MCAO), the administration of MA-5 reduced neurological deficits and infarct volume. In addition, MA-5 suppressed the increase in the Bax/Bcl-2 ratio, an index of mitochondria-mediated Apoptosis after t-MCAO. Taken together, these results suggest that MA-5 may be a useful therapeutic agent against ischemic stroke by activating mitochondrial function.

Brain; Ischemic stroke; Mitochondria; Neuron; Oxygen-glucose deprivation/reoxygenation (OGD/R).