Anti-inflammatory and Antiapoptotic Effects of Mesenchymal Stem Cells Transplantation in Rat Brain with Cerebral Ischemia

Background: Excessive inflammation and apoptosis contribute to the pathogenesis of ischemic brain damage. Nuclear factor-kappa B (NF-kappa B) is considered to be a key protein complex involved in this cascade of events. The aim of the present study was to clarify the protection mechanism of the mesenchymal stem cells (MSCs). Methods: Lewis rats (N = 90) were randomly assigned to three groups: (1) the sham-operated group; (2) the saline group, in which the animals underwent rat transient middle cerebral artery occlusion (tMCAO, for 2 hours) and were treated with saline through the tail vein; and (3) the MSCs group, in which the animals underwent tMCAO (for 2 hours) and were infused with cultured human MSCs (4 x 10(6)/0.4 ml PBS) through the tail vein. At days 1 and 3 post-MSCs infusion, real-time PCR, and Western blot, immunohistochemical analyses were applied for tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and P-IKK beta, p53, and B-cell lymphoma 2 (Bcl-2) expression levels. Results: TNF-alpha, IL-1 beta messenger RNA (mRNA) and P-IkB-alpha, P-IKK beta, p53 protein expression levels were significantly increased in the saline group compared with the sham group. However, IkB-alpha and Bcl-2 protein expression levels were markedly decreased in the saline group. After injection of BrdU 1 MSCs, the expression levels of TNF-alpha, IL-1 beta mRNA and P-IkB-alpha, P-IKK beta, p53 protein were significantly decreased. Contrary to these findings, IkB-alpha, Bcl-2 protein expression levels were markedly increased. In addition, we found that infarct area was significantly reduced in MSCs group. Conclusions: These results suggest that MSCs' neuroprotection is attributable to its anti-inflammatory and antiapoptotic effect through inhibition of NF-kappa B.