The Effect of Exosomes Derived from Bone Marrow Stem Cells in Combination with Rosuvastatin on Functional Recovery and Neuroprotection in Rats After Ischemic Stroke

Rosuvastatin, known as a cholesterol-lowering agent, has been used as an alternative therapy after the onset of stroke. In this study, neuroprotection and functional recovery of exosomes in combination with rosuvastatin have been investigated. Sixty adult male Wistar rats were subjected to middle cerebral artery occlusion (MCAO). Exosome at the dose of 100 mu g and/or rosuvastatin at the dose of 20 mg/kg/day for 7 days were administered to rats as a therapeutic strategy. The elevated body swing test (EBST) and Garcia score were conducted as behavioral tests for the measurement of functional recovery. The histopathological and immunohistochemical analyses were also performed for the assessment of infarcted volume and neuroprotection in the brain of rats. The real-time PCR method was carried out to determine the relative expressions of the NLRP-3 and NLRP1 genes. After 7 days of treatment with exosome and rosuvastatin in rats which underwent MCAO, the decrease in infarct volume of the animals treated with exosome was more pronounced compared with those treated only with exosome. The combination therapy remarkably lowered the size of infarct volume. Our observation was confirmed by the downregulation of the NLRP1 and NLRP3 genes in response to combinatory treatment of rats induced by MCOA, denoting a lower rate of cell death. The number of GFAP-positive cells were reduced in the exosome-treated group compared with the MCAO group. The rate of lipid peroxidation was measured by malondialdehyde (MDA) levels which demonstrated a significant reduction of MDA in the exosome- and rotuvastatin-treated groups when compared with the MCAO group. However, the levels of the SOD enzyme did not significantly alter when the treatment groups were compared with the MCAO group. According to our findings, it seems that the use of exosomes and rosuvastatin, as a novel treatment regimen, might promote neurological recovery after the onset of stroke.