Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada.
J Neuroinflammation. 2012 Sep 21;9:224. doi: 10.1186/1742-2094-9-224.
Evidence suggests that the inflammatory events in the acute phase of spinal cord injury (SCI) exacerbate the initial trauma to the cord leading to poor functional recovery. As a result, minimizing the detrimental aspects of the inflammatory response after SCI is a promising treatment strategy. In this regard, immunoglobulin G (IgG) from pooled human serum is a promising treatment candidate. Due to its putative, though poorly characterized immuno-modulatory effects, IgG has been used clinically to treat neuroinflammatory disorders such as Guillain-Barré syndrome, but its effects in neurotrauma remain largely unexplored.
This study examines the potential neuroprotective effects of IgG in a well-characterized cervical model of SCI. Female Wistar rats were subject to moderate-severe clip compression injury at the C7-T1 level. IgG (0.4 g/kg) or saline was injected intravenously to randomly selected animals at 15 min post SCI. At several time points post SCI, biochemical assays, histology and immunohistochemistry analyses, and neurobehavioral assessments were used to examine the neuroprotective effects of IgG at the molecular, cellular, and neurobehavioral levels.
We found that intravenous treatment of IgG following acute clip-compression SCI at C7-T1 significantly reduced two important inflammatory cytokines: interleukin (IL)-1β and IL-6. This early reduction in pro-inflammatory signaling was associated with significant reductions in neutrophils in the spinal cord and reductions in the expression of myeloperoxidase and matrix metalloproteinase-9 in the injured spinal cord at 24 h after SCI. These beneficial effects of IgG were associated with enhanced tissue preservation, improved neurobehavioral recovery as measured by the BBB and inclined plane tests, and enhanced electrophysiological evidence of central axonal conduction as determined by motor-evoked potentials.
The findings from this study indicate that IgG is a novel immuno-modulatory therapy which shows promise as a potential treatment for SCI.
有证据表明，脊髓损伤（SCI）急性期的炎症事件会加剧脊髓的初始创伤，导致功能恢复不良。因此，最大限度地减少 SCI 后炎症反应的不利方面是一种有前途的治疗策略。在这方面，来自人血清的免疫球蛋白 G（IgG）是一种很有前途的治疗候选物。由于其潜在的、但特征描述不佳的免疫调节作用，IgG 已在临床上用于治疗神经炎症性疾病，如格林-巴利综合征，但它在神经创伤中的作用仍在很大程度上未被探索。
本研究在一种经过充分特征描述的颈段 SCI 模型中研究了 IgG 的潜在神经保护作用。雌性 Wistar 大鼠在 C7-T1 水平接受中度至重度夹压伤。在 SCI 后 15 分钟，随机选择动物静脉注射 IgG（0.4 g/kg）或生理盐水。在 SCI 后的几个时间点，使用生化测定、组织学和免疫组织化学分析以及神经行为评估，在分子、细胞和神经行为水平上检查 IgG 的神经保护作用。
我们发现，在 C7-T1 处的急性夹压 SCI 后静脉内给予 IgG 治疗，显著降低了两种重要的炎症细胞因子：白细胞介素（IL）-1β和 IL-6。这种早期的促炎信号减少与脊髓内中性粒细胞的显著减少以及 SCI 后 24 小时受伤脊髓中髓过氧化物酶和基质金属蛋白酶-9表达的减少有关。IgG 的这些有益作用与组织保存的改善、BBB 和斜面测试测量的神经行为恢复的改善以及运动诱发电位确定的中央轴突传导的增强电生理证据有关。
本研究的结果表明，IgG 是一种新型的免疫调节治疗方法，有望成为 SCI 的潜在治疗方法。
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