Brain Microvascular Endothelial Cell-Derived Exosomes Protect Neurons from Ischemia-Reperfusion Injury in Mice.

ABSTRACT

Stroke often results in neurological and neuropsychiatric sequela. Exosomes derived from brain endothelial cells (EC-Exo) protect neurons from hypoxic injury. However, the biological role of exosomes in apoptosis and synaptic plasticity remains unclear. This research aimed to assess whether cerebral microvascular endothelial cells inhibit apoptosis and promote synaptic remodeling through exosome-mediated cell-cell interaction after the ischemic attack. The effects of EC-Exo on primary neuronal apoptosis and synapses in oxyglucose deprivation reoxygenation (OGD/R) injury were first assessed in vitro. Animal experiments were performed using C57BL/6J mice, divided into three groups a sham group, a model (middle cerebral artery occlusion/reperfusion, MCAO/R) group, and an EC-Exo group (tail vein injection of EC-Exo, once/2 days for 14 days) to evaluate the neuromotor and exploratory abilities of mice after MCAO/R. Apoptosis and synaptic protein expression levels were detected. The results demonstrated that EC-Exo inhibited neuronal apoptosis and increased synaptic length after OGD/R. In vivo, EC-Exo not only improved neural motor behavior and increased regional cerebral blood flow (rCBF) in MCAO/R-injured mice but also promoted the expression of synaptic regulatory proteins and inhibited apoptosis in the brain. These results suggest that EC-Exo may provide neuroprotection against stroke by promoting synaptic remodeling and inhibiting apoptosis from protecting neurons.