Mesenchymal Stem Cells Improve Ischemic Stroke Injury by Anti-Inflammatory Properties in Rat Model of Middle Cerebral Artery Occlusion

Background: Ischemic stroke is a major cause of permanent disability and inflammation has a prominent role in stroke pathology. Stem cell therapy is a new approach for stroke treatment. Mesenchymal stem cells (MSCs) are appropriate for this approach due to neuroprotective and immunomodulatory effects. Objectives: In this experimental study, the neuroprotective effects of mesenchymal stem cells (MSCs) on brain injury after transient middle cerebral artery occlusion (tMCAO) in rats was investigated with emphasis on inflammatory factors. Methods: Mesenchymal Stem Cells were isolated from bone marrow of rats and expanded by cell culture. Thirty-six male Wistar rats were randomly selected and divided to 6 groups. The MCAO model was performed in 4 groups with 24 and 72 hours of reperfusion. A single infusion of 2 x 10(6) MSCs was transplanted in one of the 24-hour and 72-hour groups and others received saline. In the sham groups, surgery was done without MCAO. Behavioral tests were evaluated and infarct volume was measured by staining of brain sections. Serumlevels of Interleukin (IL)1 beta and Tumornecrosis factor (TNF)alpha were measured by the enzymelinked immunosorbent assay (ELISA). Relative expression of Interleukin (IL)1 beta, tumor necrotizing factor (TNF)alpha, and IL6 genes were assessed in penumbra of the ischemic region using real time polymerase chain reaction (PCR). Results: The study results indicated that total behavioral scores were increased 72 hours after MSC transplantation (14.5 +/- 2.0, P < 0.01). Moreover, MSCs decreased the infarct volume both 24 hours (18.82 +/- 1.58, P < 0.01) and 72 hours (14.4 +/- 1.53, P < 0.05) after MCAO. Serum levels of IL-1 beta and TNF alpha were increased afterMCAO, yet MSCs transplantation decreased IL-1 beta (368.3 +/- 109.5, P < 0.001) and TNF alpha (126.9 +/- 38.6, P < 0.01) compared to saline. Also, relative gene expression of IL1 beta, TNF alpha, and IL6 was decreased by MSCs transplantation (P < 0.05). Conclusions: The MSCs had a neuroprotective effect in ischemic stroke via modulation of inflammatory response, and serum levels of IL1 alpha and TNF beta could be used as markers for evaluating anti-inflammatory effects of MSCs.