Neuroprotective effects of interleukin-10 following excitotoxic spinal cord injury
Neuroprotective effects of interleukin-10 following excitotoxic spinal cord injury
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DOI：
10.1006/exnr.1999.7173
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发表时间：
1999-10-01
影响因子：
5.3
通讯作者：
Yezierski, RP
中科院分区：
文献类型：
--
作者：
Brewer, KL;Bethea, JR;Yezierski, RP
使君子酸（QUIS）椎管内注射产生兴奋性毒性损伤，其病理特征与缺血性和创伤性脊髓损伤（SCI）相关的病理特征相似。炎症反应似乎是SCI引起的继发性神经元损伤的主要组成部分，并在QUIS诱导的损伤的发病机制中起作用。IL-10是一种有效的炎症细胞因子，已显示在人类和动物炎症疾病模型中减少炎症并改善功能结果。我们建议在兴奋毒性SCI后给予IL-10将减弱炎症反应，从而导致神经元存活增加。雌性Sprague-Dawley大鼠脊柱内注射QUIS，然后脊柱内（5 ng，n = 8）或全身注射（5 μ g，n = 14）IL-10。存活时间是不同的（2-3天），以产生一系列的损伤状态和炎症参与。当椎管内给药时，IL-10显著加重了QUIS损伤（P < 0.05），导致病变体积增加11.2%。当全身给予IL-10时，在更晚期的损伤中，损伤体积显著减小18.1%（P < 0.05），但对更急性的损伤没有影响。这些不同的影响归因于短期损伤中的适度炎症反应，而更慢性损伤中的炎症反应更强烈。总之，通过全身给予IL-10减少对SCI的炎症反应导致神经元损伤的显著减少，这表明靶向损伤诱导的炎症可能是急性SCI的有效治疗策略。(C)北京：科学出版社.
Intraspinal injection of quisqualic acid (QUIS) produces excitotoxic injury with pathological characteristics similar to those associated with ischemic and traumatic spinal cord injury (SCI). Inflammatory responses appear to be a major component of the secondary neuronal injury initiated by SCI and play a role in the pathogenesis of QUIS-induced injury. IL-10 is a potent antiinflammatory cytokine that has been shown to reduce inflammation and improve functional outcome in human and animal models of inflammatory diseases. We propose the administration of IL-10 following excitotoxic SCI will attenuate the inflammatory response, thus resulting in increased neuronal survival. Female, Sprague-Dawley rats were given intraspinal injections of QUIS followed by either intraspinal (5 ng, n = 8) or systemic injections (5 mu g, n = 14) of IL-10. Survival times were varied (2-3 days) in order to produce a range of injury states and inflammatory involvement. When administered intraspinally, IL-10 significantly exacerbated the QUIS damage (P < 0.05), resulting in an 11.2% increase in lesion volume. When given systemically, IL-10 significantly decreased lesion volume by 18.1% in the more advanced injury (P < 0.05), but did not effect the more acute injury. These divergent effects were attributed to the modest inflammatory response in the short-term injury compared to the more robust inflammatory response in the more chronic injury. In conclusion, reducing the inflammatory response to SCI by systemic administration of IL-10 resulted in a significant reduction in neuronal damage, suggesting that targeting injury-induced inflammation may be an effective treatment strategy for acute SCI. (C) 1999 Academic Press.