Neuroprotective Effect of Stroke Pretreated Mesenchymal Stem Cells Against Cerebral Ischemia/Reperfusion Injury in Rats

Abstract

Mesenchymal stem cells (MSCs) have been shown to enhance neurological recovery after stroke. A rat middle cerebral artery occlusion model was designed to assess neuroprotective effects of stroke pretreated MSCs on cerebral ischemia/reperfusion injury. MSCs were isolated and cultured in medium with 10% fetal bovine serum, normal control serum, or stroke serum (SS). MSCs were then injected into rats (n=6 in each group) 1 day after middle cerebral artery occlusion, and feeding continued for 28 days. A battery of behavioral tests, 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, enzyme-linked immunosorbent assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to assess neural injury. To detect enhancement of neuronal regeneration and angiogenesis, immunofluorescence and Western blotting were performed to assess expression of trophic factors and growth factors. After treatment, behavior of rats improved significantly. Infarction area, brain lesion, and apoptosis cells were significantly decreased in the SS-MSCs group compared with the other groups. SS-MSCs also modulated inflammation by attenuating inflammatory cytokines. Furthermore, the number of neurogenesis-positive cells and expression of trophic factors and growth factors were significantly higher in the SS-MSCs group compared with the others. MSCs cultured with fetal bovine serum and normal control serum showed differences in expression of trophic factors and growth factors, but the results were not as good as with SS-MSCs. Administration of SS-MCSs after reperfusion led to neuroprotection by inducing the recovery process, including improving pathological changes, behavioral improvement, neurogenesis, suppression of apoptosis and inflammation, and angiogenesis.