Abstract: Objective To investigate the cognitive change in electrical stimulation (ECS) pre-conditioned rats after traumatic brain injury (TBI) and the role of endothelial progenitor cells in brain trauma. Methods Adult male Wistar rats were divided into 4 groups randomly: Sham group (n = 61), TBI group (n = 61), ECS pre-conditioned and TBI group (ECS-TBI group, n = 61), ECS group (n = 61). At 3 h, 6 h, 24 h, 48 h, 72 h after fluid percussion injury (FPI), 6 rats were randomly selected from each group and the number of circulating endothelial progenitor cells was counted by flow cytometry. At the same time, 3 rats from each group were chosen randomly and brain tissue was taken out. Microvascular density (MVD) of injured hippocampus was measured by vWF immunohistochemical staining. Ten rats of each group were subjected to Morris Water Maze Test and escaping latencies were recorded separately at 7-11 days after FPI. Results Compared with TBI group, the number of endothelial progenitor cells in peripheral circulation increased significantly in ECS-TBI group at 3 hours and 6 hours after brain trauma (P = 0.000, for all), and reduced to baseline gradually afterwards. The vWF+ MVD on the injured side of hippocampus in ECS-TBI group was higher than those of other groups 1d after FPI, and reached to a peak at 7 d (P < 0.01). In Morris Water Maze Test, the escaping latency of ECS-TBI rats were reduced significantly compared to that of the TBI group from 3 d to 5 d after brain trauma (P < 0.01). Conclusion Compared to TBI group, there was less cognitive defect in ECS-TBI group after traumatic brain injury. This protective effect may partially due to enhanced angiogenesis induced by increasing circulating endothelial progenitor cells after ECS. Endothelial progenitor cells accumulated in the injured brain may promote post?traumatic angiogenesis and recovery of neurological function.

Key words: Transcutaneous electric nerve stimulation, Brain injuries, Stem cells, Endothelial cells, Cognition disorders, Prognosis

摘要： 目的 探讨非创伤性（电刺激）动员外周血内皮祖细胞对大鼠颅脑创伤后认知功能的影响及其可能机制。方法 于电刺激后24 h 对成年雄性Wistar大鼠施行液压打击术，制备颅脑创伤模型，流式细胞术测量创伤后外周血内皮祖细胞数量；免疫组织化学染色观察患侧海马区血管性血友病因子表达阳性（vWF+）微血管密度；Morris 水迷宫实验评价大鼠伤后认知功能恢复程度。结果 与单纯打击组比较，创伤后3 h 和6 h 电刺激预处理组大鼠外周血内皮祖细胞数量显著升高（均P = 0.000），之后逐渐降至正常水平；与其他各组相比，伤后第1 天电刺激预处理组大鼠海马区vWF+微血管密度即开始增加，至第7 天达高峰平台期（P = 0.000）；与单纯打击组相比，Morris水迷宫实验训练第3 天时电刺激预处理组大鼠逃避潜伏期开始缩短，随着训练时间的延长，组间差异明显增加且具有统计学意义（P = 0.016）。结论 电刺激预处理可促进颅脑创伤后认知功能的恢复。其潜在的机制可能与创伤前动员机体外周血内皮祖细胞，使得伤后更多的内皮祖细胞归巢到损伤区域，有助于伤后血管新生和神经功能的恢复。

关键词: 经皮神经电刺激, 脑损伤, 干细胞, 内皮细胞, 认知障碍, 预后