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Insulin-like Growth Factor-1 to Improve Neurological Recovery after Acute Spinal Cord Injury: A Porcine Study.

机译：胰岛素样生长因子-1改善急性脊髓损伤后的神经功能恢复：一项猪研究。

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摘要

Objective: Spinal cord injury is a devastating condition that leads to long-term disabilities. Currently, there is no effective treatment that minimizes spinal cord damage or enhances neurological recovery. Recent studies in rats or rabbits suggested that neurologic recovery after spinal cord injury could be improved with the administration of neurotropic hormones, such as insulin-like growth factor-1 (IGF-1). In order to apply such bench-side discovery to clinical practice, we conducted a study in a higher animal model, akin to human physiology, to evaluate the effectiveness of intrathecal injections of IGF-1to improve neurological recovery in a porcine model of acute traumatic spinal cord injury.;Methods: Traumatic spinal cord injury model was produced by controlled compression and distraction of the exposed T12 segment of the spinal cord. Eighteen pigs were randomly assigned to receive intrathecal injections of either IGF-1, growth hormone or saline at 1, 24 and 48 hours after spinal cord injury. Locomotor function was assessed daily using the validated modified Tarlov's scale for 21 days. Spinal cord segments were then harvested and the survival of neurons, reactive astrogliosis and apoptosis were determined using neuronal-specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), cleaved caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assays.;Results: Intrathecal injections of IGF-1 and growth hormone significantly increase the concentrations of the neurotropic hormones in the cerebrospinal fluid after injury (p < 0.01). These concentrations returned to baseline by 21 days after drug delivery. Motor deficits on the first day after injury were comparable between animals in the treatment and control groups. By the end of the third week, neurologic recovery was better in animals receiving IGF-1 treatment (p < 0.05). Immunohistological and western blot studies of the injured segments of spinal cord showed that treatment with both IGF-1 and growth hormone prevented reactive astrogliosis (p < 0.05) while only IGF-1 improved the survival of mature neurons (p < 0.05). IGF-1 also inhibited apoptosis after spinal cord injury (p < 0.05).;Conclusions: In our clinically relevant model of traumatic spinal cord injury in pigs, intrathecal injection of IGF-1 demonstrated beneficial effects on neurological and histological recovery.
机译：目的：脊髓损伤是导致长期残疾的毁灭性疾病。当前，没有使脊髓损伤最小化或增强神经恢复的有效治疗。最近在大鼠或兔子中进行的研究表明，通过施用诸如胰岛素样生长因子-1（IGF-1）之类的神经营养激素可以改善脊髓损伤后的神经系统恢复。为了将这种台式发现应用于临床实践，我们在类似于人类生理学的更高动物模型中进行了一项研究，以评估鞘内注射IGF-1改善猪急性脊髓损伤模型中神经系统恢复的有效性。方法：创伤性脊髓损伤模型是通过控制性压缩和牵开暴露的脊髓T12节段而建立的。十八只猪被随机分配在脊髓损伤后1、24和48小时接受鞘内注射IGF-1，生长激素或生理盐水。每天使用经过验证的改良的Tarlov量表评估运动功能，持续21天。然后收获脊髓节段，并使用神经元特异性核蛋白（NeuN），神经胶质原纤维酸性蛋白（GFAP），裂解的caspase-3和末端脱氧核苷酸转移酶介导的dUTP-生物素缺口测定神经元的存活，反应性星形胶质细胞增生和凋亡。结果：鞘内注射IGF-1和生长激素可显着增加损伤后脑脊液中的神经营养激素浓度（p <0.01）。这些浓度在给药后21天回到基线。损伤后第一天的运动缺陷在治疗组和对照组的动物之间相当。到第三周结束时，接受IGF-1治疗的动物的神经功能恢复更好（p <0.05）。脊髓损伤部分的免疫组织学和蛋白质印迹研究表明，IGF-1和生长激素的治疗​​均可以预防反应性星形胶质细胞增生（p <0.05），而只有IGF-1可以提高成熟神经元的存活率（p <0.05）。 IGF-1还抑制脊髓损伤后的细胞凋亡（p <0.05）。结论：在我们临床上相关的猪创伤性脊髓损伤模型中，鞘内注射IGF-1对神经和组织学恢复具有有益作用。

著录项

  • 作者

    Wang, Qinzhou.;

  • 作者单位

    The Chinese University of Hong Kong (Hong Kong).;

  • 授予单位 The Chinese University of Hong Kong (Hong Kong).;
  • 学科 Health Sciences General.;Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 2012
  • 页码 150 p.
  • 总页数 150
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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