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

Abstract

Excessive inflammation and apoptosis contribute to the pathogenesis of ischemic brain damage. Nuclear factor-kappa B (NF-κB) 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). 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 × 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-α (TNF-α), interleukin-1β (IL-1β) and P-IKKβ, p53, and B-cell lymphoma 2 (Bcl-2) expression levels. TNF-α, IL-1β messenger RNA (mRNA) and P-IκB-α, P-IKKβ, p53 protein expression levels were significantly increased in the saline group compared with the sham group. However, IκB-α and Bcl-2 protein expression levels were markedly decreased in the saline group. After injection of BrdU(+) MSCs, the expression levels of TNF-α, IL-1β mRNA and P-IκB-α, P-IKKβ, p53 protein were significantly decreased. Contrary to these findings, IκB-α, Bcl-2 protein expression levels were markedly increased. In addition, we found that infarct area was significantly reduced in MSCs group. These results suggest that MSCs' neuroprotection is attributable to its anti-inflammatory and antiapoptotic effect through inhibition of NF-κB.