亚低温下脑缺血大鼠骨髓间充质干细胞迁移和梗死体积的变化

背景：关于亚低温运用到神经损伤修复领域的研究已有一些报道,但亚低温对神经干细胞在脑内移植迁移的影响还不太清楚。 目的：观察亚低温对移植入脑缺血大鼠侧脑室的骨髓间充质干细胞迁移及脑梗死体积的影响。 方法：采用Longa法永久性闭塞SD大鼠大脑中动脉制作局灶性脑缺血损伤模型,50只大鼠随机摸球法分为亚低温组、对照组、假手术组。亚低温组于移植前应用亚低温处理大鼠急性脑缺血损伤,对照组于移植前应用常温处理大鼠急性脑缺血损伤;假手术组大鼠麻醉后分离结扎右侧颈内总动脉。亚低温组和对照组在造模后24 h,在脑立体定向下经侧脑室注射移植用5-BrdU标记的骨髓间充质干细胞。经过5,14,21 d后用免疫组织化学方法检测各组大鼠脑组织BrdU阳性细胞数。 结果与结论：骨髓间充质干细胞移植第14天多数标记的骨髓间充质干细胞已经迁移至梗死灶周围,移植后亚低温组各时间点梗死灶周边皮质的BrdU阳性细胞数明显多于对照组(P < 0.05)。与对照组比较,亚低温组在移植前后各个时间点脑梗死体积均显著减小(P < 0.05)。提示移植前宿主亚低温处理可以促进骨髓间充质细胞的定向迁移,且脑梗死体积显著减小。

Migration of bone marrow mesenchymal stem cells and changes in infarct volume in rats with cerebral ischemia under mild hypothermia

BACKGROUND:There are a few reports addressing the application of mild hypothermia to the study of repairing the nerve injury, but few reports have addressed the effects of mild hypothermia on the migration of neural stem cells in the brain following transplantation. OBJECTIVE:To explore the effects of mild hypothermia on the migration of bone marrow mesenchymal stem cells transplanted into the lateral ventricle of rats with cerebral ischemia, as well as the effect on the infarct volume. METHODS:A focal cerebral ischemic injury model of right middle cerebral artery occlusion was established using modified Longa’s method in Sprague-Dawley rats. Fifty rats were divided into mild hypothermia group, control group and sham-operation group. Local mild hypothermia was applied in the mild hypothermia group before transplantation for the treatment of acute cerebral ischemia. Normal body temperature was maintained in control group before transplantation for the treatment of acute cerebral ischemia. The right carotid artery of rats in the sham-operation group was separated and ligated after anesthesia. At 24 hours following model establishment in the mild hypothermia group and the control group, bone marrow mesenchymal stem cells labeled with 5-BrdU were transplanted into the rat lateral ventricle. The amount of BrdU-positive cells in the brain tissue in each group was measured by immunohistochemistry at 5, 14 and 21 days following injection in each group.   RESULTS AND CONCLUSION:At 14 days after transplantation, a majority of labeled bone marrow mesenchymal stem cells had migrated to the infarct area. At various time points following transplantation, the number of BrdU-positive cells in the cortex around infarction focus was obviously greater in the hypothermia group compared with the control group  (P < 0.05). Compared with the control group, the infarct volume in the mild hypothermia group at various time points was reduced significantly (P < 0.05). Results indicate that mild hypothermia before transplantation may promote the direct migration of bone marrow mesenchymal stem cells, and can reduce the infarct volume.