Mahmood Asim, Lu Dunyue, Qu Changsheng, Goussev Anton, Chopp Michael
Department of Neurosurgery, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Neurosurgery. 2005 Nov;57(5):1026-31; discussion 1026-31. doi: 10.1227/01.neu.0000181369.76323.50.
This study was designed to investigate the effects of human bone marrow stromal cell (hMSC) administration in rats for 3 months after traumatic brain injury (TBI).
Adult male Wistar rats (n = 60) were injured with controlled cortical impact and divided into four groups. The three treatment groups (n = 10 each) were injected with 2 x 10, 4 x 10, and 8 x 10 hMSCs, respectively, intravenously, whereas the control group (n = 30) received phosphate-buffered saline. All injections were performed 1 day after injury into the tail veins of rats. Neurological functional evaluation of animals was performed before and after injury by use of Neurological Severity Scores. Animals were sacrificed 3 months after TBI, and brain sections were stained by immunohistochemistry.
Statistically significant improvement in functional outcome was observed in all three treatment groups compared with control values (P < 0.05). This benefit was visible 14 days after TBI and persisted until 3 months (end of trial). There was no difference in functional outcome among the three treatment groups. Histological analysis showed that hMSCs were present in the lesion boundary zone at 3 months with all three doses tested.
hMSCs injected in rats after TBI survive until 3 months and provide long-lasting functional benefit. Functional improvement may be attributed to stimulation of endogenous neurorestorative functions such as neurogenesis and synaptogenesis.
本研究旨在探讨创伤性脑损伤(TBI)后3个月给大鼠注射人骨髓间充质干细胞(hMSC)的效果。
成年雄性Wistar大鼠(n = 60)采用控制性皮质撞击致伤,并分为四组。三个治疗组(每组n = 10)分别经静脉注射2×10、4×10和8×10的hMSC,而对照组(n = 30)接受磷酸盐缓冲盐水。所有注射均在大鼠受伤后1天经尾静脉进行。在受伤前后通过神经严重程度评分对动物进行神经功能评估。TBI后3个月处死动物,脑切片进行免疫组织化学染色。
与对照值相比,所有三个治疗组的功能结局均有统计学意义的改善(P < 0.05)。这种益处于TBI后14天可见,并持续至3个月(试验结束)。三个治疗组之间的功能结局无差异。组织学分析显示,在3个月时,在所测试的所有三种剂量下,hMSC均存在于损伤边界区。
TBI后给大鼠注射的hMSC可存活至3个月,并提供持久的功能益处。功能改善可能归因于对内源性神经修复功能如神经发生和突触发生的刺激。