骨髓间充质干细胞立体定向移植联合亚低温治疗大鼠脑损伤

背景:临床研究证明,亚低温(33~35℃)能有效减轻继发性脑和脊髓损伤,对中枢神经损伤有确切的保护作用。目的:检测是否可以通亚低温治疗的方法提高骨髓间充质干细胞立体定向移植对重型颅脑损伤大鼠的治疗效果。方法:采用液压颅脑损伤仪,给予Wistar大鼠2.53.31~303.98kPa液压冲击力,制成重型液压颅脑损伤大鼠模型,将其随机分为脑损伤组,骨髓间充质干细胞移植组,亚低温+骨髓间充质干细胞组。后2组伤后6h将体外培养的SD大鼠骨髓间充质干细胞立体定向移植到脑损伤灶内,亚低温+骨髓间充质干细胞组同时给予低温治疗。伤后第3天用WesternBlot检测脑组织中AQP4蛋白合成的变化,采用干湿比重法测脑组织含水量。伤后24h,3d及伤后1,2周行动物神经学缺损评分,2周后处死行免疫组织化学和苏木精-伊红染色。结果与结论:亚低温治疗后,与脑损伤组和骨髓间充质干细胞移植组相比,亚低温+骨髓间充质干细胞组AQP4蛋白表达量及脑水肿程度也明显降低(P<0.05),移植后1和2周,亚低温+骨髓间充质干细胞组的大鼠神经学缺损评分明显低于其他两组;且其脑组织切片中的神经元数量较其他两组明显增多(P<0.01)。提示骨髓间充质干细胞立体定向移植联合亚低温治疗大鼠脑损伤可明显改善重型颅脑损伤后大鼠的神经学功能。

Stereotactic transplantation of bone marrow mesenchymal stem cells combined with mild hypothermia for traumatic brain injury

BACKGROUND:In recent years,mild hypothermia(33-35 ℃) in the treatment of brain and spinal cord injury obtains more and more attention.Many clinical studies have shown that mild hypothermia can reduce secondary brain and spinal cord injury,and play a precise protective role in central nervous injury in rats.OBJECTIVE:To determine whether mild hypothermia can enhance curative effects of stereotactic transplantation of bone marrow mesenchymal stem cells(BMSCs) on traumatic brain injury(TBI) in rats.METHODS:BMSCs were cultured by the suspension culture in vitro.The models of severe TBI were made in rats by given 253.31-303.98 kPa power of hydraulic impact.BMSCs were stereotactically transplantated into the brain in the rats with TBI 24 hours after TBI,and the rats were divided into three groups,group A:TBI;group B:BMSCs transplantation group;group C:BMSCs transplantation+hypothermia group.After 3 days,AQP4 expression was determined by Western Blot,the water contents in the brain tissues were measured as wet-to-dry weight ratio.The neurological defect scores were determined after 24 hours,3 days and 1,2 weeks after TBI.The immunohistochemistry and pathology were checked after 2 weeks.RESULTS AND CONCLUSION:Three days after brain injury,compared with A group and B group,the expression of AQP4 detected by Western Blot and cerebral edema detected by wet-to-dry weight ratio were decreased(P<0.05).The neurological defect scores were significantly lower in group C than those in groups A and B at 1 and 2 weeks after TBI(P<0.05).The number of neurons in group C was higher than that in groups A and B(P<0.01).These findings show that stereotactic transplantation of BMSCs combined with mild hypothermia can significantly improve the neurological function in the rats with TBI.