Effects of bone marrow mesenchymal stem cells transplantation on the recovery of neurological functions and the expression of Nogo-A, NgR, Rhoa, and ROCK in rats with experimentally-induced convalescent cerebral ischemia

骨髓间充质干细胞移植对实验诱导的恢复期脑缺血大鼠神经功能恢复及Nogo-A、NgR、Rhoa和ROCK表达的影响

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Abstract

BACKGROUND: To investigate the effects of intravenous transplantation of bone marrow mesenchymal stem cells (BMSCs) on neurological function in rats with experimentally-induced convalescent cerebral ischemia and the expression of Nogo-A, NgR, Rhoa, and ROCK expression. METHODS: BMSCs were isolated and cultured in vitro using the whole bone marrow adherent method. Eighty-one adult male Sprague-Dawley rats were divided at random into three groups: the sham-operated group, the cerebral ischemia group, and the BMSC treatment group (n=27 rats per group). In the latter two groups, the middle cerebral artery occlusion (MCAO) model was performed by the modified Zea Longa method. After MCAO, rats in the sham-operated and cerebral ischemic groups were injected with 1 mL of phosphate buffered saline (PBS) via the tail vein. In the BMSC-treatment group, 1 mL of the BMSC suspension (containing 3×10(6) BMSCs) was injected through the rats' femoral vein. At 12, 24, and 72 h after BMSC transplantation, modified neurological deficit scores (mNSS) were used to assess neurological function. TTC (2,3,5-triphenyl tetrazolium chloride) staining was used to measure the ischemic lesion volume, and the distribution of Nogo-A protein was observed by immunohistochemistry. The expressions of Nogo-A, NgR, Rhoa, and ROCK were detected by Western blot. RESULTS: At 72 h after BMSC transplantation, the mNSS scores were significantly lower in the BMSC treatment group than those in the cerebral ischemia group (7.50±0.55 vs. 8.67±0.52, P<0.01), and the ischemic lesions volume was significantly reduced. The expressions of Nogo-A, NgR, RhoA, and ROCK were significantly decreased compared with the controls (P<0.05). CONCLUSIONS: The transplantation of BMSCs can improve neurological function in rats after convalescent cerebral ischemia, and their therapeutic effect may be related to the downregulation of Nogo-A, NgR, RhoA, and ROCK expression.

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