...
首页> 外文期刊>The European Journal of Neuroscience >Neutralization of interleukin-1beta modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice.
【24h】

Neutralization of interleukin-1beta modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice.

机译:白细胞介素-1β的中和改变了小鼠颅脑外伤后的炎症反应并改善了组织学和认知结果。

获取原文
获取原文并翻译 | 示例
           

摘要

Interleukin-1beta (IL-1beta) may play a central role in the inflammatory response following traumatic brain injury (TBI). We subjected 91 mice to controlled cortical impact (CCI) brain injury or sham injury. Beginning 5 min post-injury, the IL-1beta neutralizing antibody IgG2a/k (1.5 microg/mL) or control antibody was infused at a rate of 0.25 microL/h into the contralateral ventricle for up to 14 days using osmotic minipumps. Neutrophil and T-cell infiltration and microglial activation was evaluated at days 1-7 post-injury. Cognition was assessed using Morris water maze, and motor function using rotarod and cylinder tests. Lesion volume and hemispheric tissue loss were evaluated at 18 days post-injury. Using this treatment strategy, cortical and hippocampal tissue levels of IgG2a/k reached 50 ng/mL, sufficient to effectively inhibit IL-1betain vitro. IL-1beta neutralization attenuated the CCI-induced cortical and hippocampal microglial activation (P < 0.05 at post-injury days 3 and 7), and cortical infiltration of neutrophils (P < 0.05 at post-injury day 7). There was only a minimal cortical infiltration of activated T-cells, attenuated by IL-1beta neutralization (P < 0.05 at post-injury day 7). CCI induced a significant deficit in neurological motor and cognitive function, and caused a loss of hemispheric tissue (P < 0.05). In brain-injured animals, IL-1beta neutralizing treatment resulted in reduced lesion volume, hemispheric tissue loss and attenuated cognitive deficits (P < 0.05) without influencing neurological motor function. Our results indicate that IL-1beta is a central component in the post-injury inflammatory response that, in view of the observed positive neuroprotective and cognitive effects, may be a suitable pharmacological target for the treatment of TBI.
机译:IL-1beta(IL-1beta)可能在脑外伤(TBI)后的炎症反应中发挥重要作用。我们对91只小鼠进行了受控的皮质撞击(CCI)脑损伤或假手术损伤。损伤后5分钟开始,使用渗透微型泵以0.25 microL / h的速率将IL-1β中和抗体IgG2a / k(1.5 microg / mL)或对照抗体注入对侧心室长达14天。在损伤后第1-7天评估中性粒细胞和T细胞的浸润以及小胶质细胞的活化。使用莫里斯水迷宫评估认知度,并使用旋转脚踏车和滚筒测试评估运动功能。在损伤后18天评估病变体积和半球组织损失。使用这种治疗策略,皮层和海马组织IgG2a / k的水平达到50 ng / mL,足以在体外有效抑制IL-1。 IL-1β中和减弱了CCI诱导的皮质和海马小胶质细胞活化(损伤后第3天和第7天的P <0.05)和嗜中性粒细胞的皮质浸润(损伤后第7天的P <0.05)。 IL-1β中和作用减弱了活化T细胞的皮质浸润(损伤后第7天P <0.05)。 CCI引起神经运动和认知功能的明显缺陷,并导致半球组织的丧失(P <0.05)。在脑损伤的动物中,IL-1β中和处理可减少病变体积,减少半球组织损失并减轻认知缺陷(P <0.05),而不会影响神经系统运动功能。我们的结果表明,IL-1β是损伤后炎症反应的主要成分,鉴于观察到的积极的神经保护和认知作用,IL-1β可能是治疗TBI的合适药理靶标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号