Neuroprotective effects of intravenous transplantation of bone marrow mononuclear cells from 5-fluorouracil pre-treated rats on ischemic stroke

• Published in: Behavioural brain research 2016-03, Vol.301, p.287-292
• Main Authors: Li, Y., Mao, W.W., Zhang, C.G., Wan, L., Jing, C.H., Hua, X.M., Li, S.T., Cheng, J.
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Animals; Bone Marrow Cells - drug effects; Bone Marrow Cells - pathology; Bone Marrow Cells - physiology; Bone marrow mononuclear cells; Bone Marrow Transplantation - methods; Brain - pathology; Brain - physiopathology; Brain Ischemia - pathology; Brain Ischemia - physiopathology; Brain Ischemia - therapy; Cell Survival; CXCR4; Disease Models, Animal; Fluorouracil - pharmacology; Growth factor; Infarction, Middle Cerebral Artery; Injections, Intravenous; Male; Nerve Growth Factors - metabolism; Neuroprotective Agents - pharmacology; Random Allocation; Rats, Sprague-Dawley; Receptors, CXCR4 - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - physiopathology; Reperfusion Injury - therapy; Stroke; Stroke - pathology; Stroke - physiopathology; Stroke - therapy
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2015.07.048

•Bone marrow mononuclear cells (BMMNCs) from 5-fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats.•BMRMNCs have elevated secretion of growth factors as compared to BMMNCs.•More BMRMNCs migrate to the injured brain early after transplantation as compared to BMMNCs. Our previous findings showed bone marrow mononuclear cells (BMMNCs) from 5- fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats. This study was undertaken to explore the potential mechanisms underlying the neuroprotective effects of BMRMNCs in middle cerebral artery occlusion (MCAO) rat model. Rats were intravenously pre-treated with 5-FU and BMRMNCs were collected at different time points. The contents of growth factors in the supernatant and CXCR4 expression were detected by ELISA and flow cytometry, respectively. MCAO was introduced to rats, and BMMNCs and BMRMNCs collected at 7 days after 5-FU pre-treatment were independently transplanted via the tail vein 24h later. The neurological function was evaluated before cell transplantation and at 24h, 7d and 14d after cell transplantation. Rats were sacrificed at 14d after cell transplantation, the brains were collected for TTC staining, infarct volume detection, NISSL staining, counting of viable cells in the CA1 region, and observation of transplanted cells. BMRMNCs had elevated expressions of growth factors as well as CXCR4 expression. Our results confirmed the better therapeutic effects of BMRMNCs in MCAO rats, demonstrated by reduction in infarct volume, improvement of neurological function and more viable cells in the hippocampus. In addition, more transplanted cells were found after BMRMNCs transplantation at 7 days and 14 days although there was no marked difference at 14 days. These findings indicate that BMRMNCs transplantation may protect ischemic stroke, at least partially, via increasing the secretion of growth factors and migration to the injured site.