骨髓基质细胞脑室内移植对脑外伤后神经功能障碍的治疗作用

Therapeutical effect of intracerebroventricular transplantation of bone marrow stromal cells in the rats subjected to experimental traumatic brain injury

目的:探讨骨髓基质细胞(MSCs)移植到实验性脑外伤大鼠侧脑室后对神经功能障碍的治疗作用。方法:从GFP转基因SD大鼠分离MSCs,体外扩增至第五代。取SD大鼠96只,供制作模型。其中随机选取24只作为正常对照组,72只采用Feeney自由落体方法建立大鼠脑外伤模型,造模后7 d,随机分为三组:MSCs治疗组、IMDM对照组、TBI对照组,每组24只。MSCs治疗组经侧脑室移植MSCs,IMDM对照组经侧脑室注射同体积的IMDM基础培养液,TBI对照组经侧脑室空白进针,分别于移植后2、4、8、12周末,以神经功能评分和免疫荧光染色评价MSCs移植后对大鼠神经功能的改善情况和在大鼠脑内存活迁移情况。结果:经侧脑室移植的MSCs可向脑损伤区域迁移,少数能表达一些神经元和星形胶质细胞的特异性标志物,如NeuN和GFAP。侧脑室移植MSCs治疗组大鼠神经功能恢复的程度优于侧脑室注射IMDM对照组和TBI对照组,有统计学差异(P<0.05),IMDM对照组和TBI对照组神经功能恢复的程度相比无明显差异(P>0.05)。结论:MSCs通过侧脑室同种异体移植后能存活并向损伤区域迁移聚集,少数可分化为神经元和星形胶质细胞,可促进外伤性脑损伤所造成的神经功能障碍的恢复。

Objective： To assess the effect of intracerebroventricular transplantation of bone marrow stromal cells（MSCs） on the improvement of neurological behavior in the rats subjected to experimental traumatic brain injury.Methods： MSCs were separated from GFP-SD rats and cultured into the fifth generation in vitro.96 SD rats were applied in the model establishments,among which 24 rats were selected as normal group,Feeney free-failing method was used to establish traumatic brain injury（TBI） models in other 72 rats,7 days after model establishment,the 72 rats were divided into MSCs transplantation group,Isore＇s Modified Dulbecco＇s Medium（IMDM） control group,TBI control group,with 24 rats in each.The MSCs transplantation rats were transplanted with MSCs into lateral ventricle.The IMDM control rats were injected with IMDM of equal volume into lateral ventricle,the TBI control rats were injected with nothing into lateral ventricle.At the end of 2,4,8 and 12 weeks of transplantations respectively,the neurological severity score（NSS） and immunohistochemical detection were used to evaluate the improvements of neurological function and migration of MSCs in vivo.Results： The MSCs immigrated to injured brain areas after lateral ventricle administration,and a few of MSCs expressed phenotypic protein marker of neural cells,such as NeuN and GFAP.The neurological scores in the MSCs transplantation group was better than that of the IMDM control and TBI control groups（P0.05）.There was no significant difference in the neurological scores between IMDM control and TBI control groups（P0.05）.Conclusion： MSCs could immigrate to injury brain areas after lateral ventricle administration and has a therapeutic benefit after TBI,and a few of MSCs could differentiate into neurons or astrocytes.