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

Jianbo Zhang; Zhenjun Li; Wenchao Liu; Wenxian Zeng; Chuanzhi Duan; Xuying He

doi:10.21037/atm.2020.03.144

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

Ann Transl Med. 2020 Mar;8(6):390. doi: 10.21037/atm.2020.03.144.

Authors

Jianbo Zhang¹, Zhenjun Li¹, Wenchao Liu¹, Wenxian Zeng¹, Chuanzhi Duan¹, Xuying He^{1

2}

Affiliations

¹ Department of Neurosurgery, The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Province Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
² Department of Neurosurgery, Southern Medical University, Zhujiang Hospital, Guangzhou 510282, China.

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 3×10⁶ 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.

Keywords: Bone marrow mesenchymal stem cells (BMSCs); Nogo-A; convalescent cerebral ischemia.