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

• Published in: Journal of stroke and cerebrovascular diseases Vol. 23; no. 10; pp. 2598 - 2606
• Main Authors: Gu, Naibing, MD, Rao, Chunguang, MD, Tian, Ye, PhD, Di, Zhengli, MD, PhD, Liu, Zhiqin, MD, Chang, Mingze, MD, Lei, Hui, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2014
• Subjects: Animals; Apoptosis; bcl-2-Associated X Protein - metabolism; Brain - metabolism; Brain - pathology; Brain Ischemia - metabolism; Brain Ischemia - therapy; Cardiovascular; Disease Models, Animal; Human mesenchymal stem cells; Humans; I-kappa B Kinase - metabolism; I-kappa B Proteins - metabolism; Infarction, Middle Cerebral Artery - complications; inflammation; Inflammation - metabolism; Interleukin-1beta - metabolism; Male; Mesenchymal Stem Cell Transplantation - methods; Neurology; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; nuclear factor-kappa B; rat cerebral ischemia and reperfusion; Rats; Rats, Inbred Lew; Treatment Outcome; Tumor Necrosis Factor-alpha - metabolism; Tumor Suppressor Protein p53 - metabolism; nuclear factor-kappa B; apoptosis; rat cerebral ischemia and reperfusion; Human mesenchymal stem cells; inflammation
• ISSN: 1052-3057; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2014.05.032

Background 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). 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 × 106 /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. Results 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. Conclusions These results suggest that MSCs' neuroprotection is attributable to its anti-inflammatory and antiapoptotic effect through inhibition of NF-κB.