Bone marrow mesenchymal stem cells may alleviate brain damage caused by the microglial overactivation in the cortex around ischemic site of stroke
Yan Nan1, Wu Yanlong2, Tang Xiaohui2, Zhang Xiaoyan2, Wang Hui2, Yang Tianze2, Zhou Maochun2, Wang Zhengdong3, Yang Xiaoxia1
1School of Medical Applied Technology, 2Basic Medical College, 3Department of Anatomy, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
Abstract: BACKGROUND: Bone marrow mesenchymal stem cell transplantation has achieved good results in the treatment of ischemic stroke, but its mechanism of action still needs to be studied in depth.
OBJECTIVE: To study the effects of bone marrow mesenchymal stem cells on further damage of overactivated microglia in the cortex around ischemic site.
METHODS: Thirty 8-week-old Sprague-Dawley rats were divided into sham operation, model, and transplantation groups. The ischemic stroke models of rats were established with blocking the middle cerebral artery with an embolic thread method for the model group and transplantation group. The third generation of bone marrow mesenchymal stem cells was injected into the abdominal cavity of the transplantation. Rabbits of the model group and the sham operation group were injected with the same amount of DMEM. The injection was taken on every other day after surgery for 14 consecutive days. The motor function of paralyzed rats in different groups was evaluated by BBB scores at 7 and 14 days after surgery. At 15 days after operation, the cortex around the cerebral infarction was taken from the rats. Immunohistochemical staining and western blot assay were applied to study the expression of Ox-42, a marker of activated microglia, and tumor necrosis factor-α, interleukin-6, and interleukin-1β in the cortex near the ischemia cortex.
RESULTS AND CONCLUSION: Compared with the sham operation group, expression levels of Ox-42 activated by microglia and tumor necrosis factor-α, interleukin-6, and interleukin-1β were higher in the model group, and decreased in the transplantation group. Compared with the model group, BBB scores showed an improved motor function of paralysis limbs in the transplantation group. It is concluded that the over-activation of microglia is inhibited, and the expression of inflammatory cytokines is decreased with bone marrow mesenchymal stem cells, thus to protect the cerebral cortex from damaging and promote motor function recovery to a certain extent.
Key words: stem cells, bone marrow mesenchymal stem cells, ischemic stroke, tumor necrosis factor-α, interleukin-6, and interleukin-1β, Ox-42