Neural Stem Cell Derived Extracellular Vesicles Pre-vents Microgliosis in Rat after Permanent Focal Ischemia

Background: Ischemic stroke is one of the most common caus-es of death and neurological disability worldwide. Neural stem cells (NSCs) have been suggested to reduce neuroinflamma-tion, in part through their secretion factors. Extracellular vesi-cles (EVs) are membrane-bound vesicles suggested to be po-tential exogenous therapeutic tools. Here, we studied whether NSC derived EVs (NSC-EVs) have anti-inflammatory effects on microglia and prevent microgliosis.Materials and Methods: EVs were isolated from neural stem cell culture by ultracentrifugation and characterized by enriched protein expression, size, and morphology. Middle cerebral oc-clusion artery (MCAO) used as rat ischemic stroke model. Sev-en days after stroke, the modified neurological severity score (mNSS) test was performed to measure functional recovery. Microglial marker Iba1 immunoreactivity was evaluated in brain coronal sections by immunohistochemistry technique in sham-injury, ischemia and EV treated groups.Results: Animals (n=3) treated with NSC-EVs significantly decreased Iba1 immunoreactivity to the baseline state. Also, displayed consistently better neurological function with mNSS score reduction.Conclusion: NSC-EVs administration prevents microgliosis in the ischemic brain and improves functional recovery.

Keywords:

MCAO , Neural Stem Cell , Extracellular Vesicle , Mi-croglia , Mnss