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亚低温联合神经干细胞移植对脊髓损伤大鼠神经功能恢复的影响。

Effects of hypothermia combined with neural stem cell transplantation on recovery of neurological function in rats with spinal cord injury.

作者信息

Wang Dong, Zhang Jianjun

机构信息

Department of Neurosurgery, The Fourth Center Clinical College of Tianjin Medical University, Tianjin 300140, P.R. China.

出版信息

Mol Med Rep. 2015 Mar;11(3):1759-67. doi: 10.3892/mmr.2014.2905. Epub 2014 Nov 10.

Abstract

The microenvironment of the injured spinal cord is hypothesized to be involved in driving the differentiation and survival of engrafted neural stem cells (NSCs). Hypothermia is known to improve the microenvironment of the injured spinal cord in a number of ways. To investigate the effect of NSC transplantation in combination with hypothermia on the recovery of rat spinal cord injury, 60 Sprague‑Dawley female rats were used to establish a spinal cord hemisection model. They were divided randomly into three groups: A, spinal cord injury group; B, NSC transplantation group; and C, NSC transplantation + hypothermia group. At 1, 2, 4, 6 and 8 weeks post‑injury, the motor function of all animals was evaluated using the Basso, Beattie and Besnaham locomotor scoring system and the inclined plane test. At 4 weeks post‑transplantation, histological analysis and immunocytochemistry were performed. At 8 weeks post‑transplantation, horseradish peroxidase nerve tracing and transmission electron microscopy were conducted to observe axonal regeneration. The outcome of hind limb motor function recovery in group C significantly surpassed that in group B at 4 weeks post‑injury (P<0.05). Recovery was also observed in group A, but to a lesser degree. For the pathological sections no neural axonal were observed in group A. A few axon‑like structures were observed in group B and more in group C. Horseradish peroxidase‑labeled neurofibers and bromodeoxyuridine‑positive cells were observed in the spinal cords of group C. Fewer of these cells were found in group B and fewer still in group A. The differences among the three groups were significant (P<0.05). Using transmission electron microscopy, newly formed nerve fibers and myelinated nerve fibers were observed in the central transverse plane in groups B and C, although these nerve fibers were not evident in group A. In conclusion, NSC transplantation promoted the recovery of hind limb function in rats, and combination treatment with hypothermia produced synergistic effects.

摘要

据推测,受损脊髓的微环境参与驱动植入神经干细胞(NSC)的分化和存活。已知低温可通过多种方式改善受损脊髓的微环境。为了研究NSC移植联合低温对大鼠脊髓损伤恢复的影响,采用60只雌性Sprague-Dawley大鼠建立脊髓半切模型。将它们随机分为三组:A组为脊髓损伤组;B组为NSC移植组;C组为NSC移植+低温组。在损伤后1、2、4、6和8周,使用Basso、Beattie和Besnaham运动评分系统和倾斜平面试验评估所有动物的运动功能。在移植后4周,进行组织学分析和免疫细胞化学检测。在移植后8周,进行辣根过氧化物酶神经追踪和透射电子显微镜观察轴突再生情况。损伤后4周时,C组后肢运动功能恢复的结果显著优于B组(P<0.05)。A组也观察到了恢复,但程度较轻。病理切片显示,A组未观察到神经轴突。B组观察到一些轴突样结构,C组更多。在C组脊髓中观察到辣根过氧化物酶标记的神经纤维和溴脱氧尿苷阳性细胞。B组中这些细胞较少,A组更少。三组之间的差异具有统计学意义(P<0.05)。使用透射电子显微镜观察发现,B组和C组在中央横切面上观察到新形成的神经纤维和有髓神经纤维,而A组未观察到明显的神经纤维。总之,NSC移植促进了大鼠后肢功能的恢复,低温联合治疗产生了协同作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/727b/4270334/7bb803da4c16/MMR-11-03-1759-g00.jpg

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