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基质细胞衍生因子-1α(SDF-1α)可改善大鼠脊髓挫伤后的神经恢复。

Stromal cell-derived factor-1 alpha (SDF-1α) improves neural recovery after spinal cord contusion in rats.

机构信息

Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Brain Res. 2012 Sep 14;1473:214-26. doi: 10.1016/j.brainres.2012.07.037. Epub 2012 Jul 27.

Abstract

Stromal cell-derived factor-1 alpha (SDF-1α) is an important cytokine, implicated in the control of stem cell trafficking and bone marrow-derived stem cell mobilization. Generally, SDF-1α regulates multiple physiological processes such as embryonic development and organ homeostasis. There is also good evidence that SDF-1α and its receptor CXCR4(1) are key regulators of neurorepair processes after brain ischemia and spinal cord injury. In this study, we investigated the influence of chronic intrathecal delivery of SDF-1α after spinal cord contusion. After contusion T9, male Wistar rats at the age of 12 weeks were intrathecally treated with SDF-1α in different doses (100, 500 and 1000 ng/ml) via an osmotic pump for 28 days. Thereafter, animals were subjected to an open field locomotor test. Behavioral scores were significantly higher in SDF-1α treated animals compared to placebo-treated groups. In addition, we evaluated histopathological changes in the spinal cord in the presence or absence of SDF-1α. Chronic delivery of SDF-1α decreased numbers of apoptotic cells, boosted astroglia and microglia response, induced angiogenesis, and potentiated the number of proliferating cells in a dose-dependent manner. These results clearly indicate an improved functional CNS long-term recovery after spinal cord injury. This behavioral restoration was paralleled by a reduction of apoptosis and changes in neuroinflammatory cells.

摘要

基质细胞衍生因子-1 阿尔法(SDF-1α)是一种重要的细胞因子,参与控制干细胞的迁移和骨髓源性干细胞的动员。通常,SDF-1α 调节多种生理过程,如胚胎发育和器官稳态。也有充分的证据表明,SDF-1α 和其受体 CXCR4(1)是脑缺血和脊髓损伤后神经修复过程的关键调节因子。在这项研究中,我们研究了脊髓挫伤后鞘内持续给予 SDF-1α 的影响。在 T9 挫伤后,12 周龄雄性 Wistar 大鼠通过渗透泵鞘内给予不同剂量(100、500 和 1000ng/ml)的 SDF-1α 28 天。之后,动物接受了旷场运动测试。与安慰剂组相比,SDF-1α 处理组的行为评分明显更高。此外,我们评估了存在或不存在 SDF-1α 时脊髓的组织病理学变化。SDF-1α 的慢性给药以剂量依赖性的方式减少了凋亡细胞的数量,增强了星形胶质细胞和小胶质细胞的反应,诱导了血管生成,并增加了增殖细胞的数量。这些结果清楚地表明,脊髓损伤后中枢神经系统的功能长期恢复得到了改善。这种行为恢复与凋亡减少和神经炎症细胞的变化相平行。

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