Bone marrow mesenchymal stem cells-derived exosomes mediated delivery of tetramethylpyrazine attenuate cerebral ischemic injury

Abstract

ObjectivesTetramethylpyrazine (TEP) can protect the brain from ischemic damage, but it has defects such as short half-life, fast absorption, wide distribution, and rapid elimination, which limits its application. Exosomes (Exos) have the property of loading drugs and transporting signal substances. Here, we elucidated the effect of TEP-loaded bone marrow mesenchymal stem cell (BMSC)-derived Exos (Exo-TEP) on cerebral ischemic injury. Materials and MethodsThe Exos were extracted by ultracentrifugation and TEP was loaded into the Exos by electroporation. Oxygen-glucose deprivation (OGD) induced-primary cortical neurons and middle cerebral artery occlusion (MCAO)-induced mouse models were used to determine the effect of Exo-TEP on cerebral ischemic injury in vitro and in vivo. ResultsExo-TEP exhibited a stable and sustained release pattern compared to free TEP. Exo-TEP treatment was more significant in improving OGD-mediated decrease in cell activity, as well as a elevation in apoptosis and ROS production in cortical neurons. In comparison with Exo and free TEP treatment, Exo-TEP treatment significantly improved pathological changes, shrunk cerebral infarction volume, as well reduced neurological deficit scores and neuronal apoptosis, and oxidative stress. ConclusionsExo-TEP was superior to free TEP in improving cerebral ischemic injury by reducing neuronal apoptosis and oxidative stress.