• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of neuroinflammation >TLR-3 receptor activation protects the very immature brain from ischemic injury
【24h】

TLR-3 receptor activation protects the very immature brain from ischemic injury

机译：TLR-3受体激活可保护未成熟的大脑免受缺血性损伤

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background We have shown that preconditioning by lipopolysaccharide (LPS) will result in 90% reduction in ischemic brain damage in P7 rats. This robust LPS neuroprotection was not observed in P3 or P5 pups (corresponding to human premature infant). LPS is a known Toll-like receptor 4 (TLR-4) ligand. We hypothesized that TLRs other than TLR-4 may mediate preconditioning against cerebral ischemic injury in the developing brain. Methods TLR-2, TLR-3, TLR-4, and TLR-9 expression was detected in brain sections from P3, P5, and P7 rats by immuno-staining. In subsequent experiments, P5 rats were randomly assigned to TLR-3 specific agonist, poly I:C, or saline treated group. At 48 h after the injections, hypoxic-ischemic (HI) injury was induced by unilateral carotid artery ligation followed by hypoxia for 65 min. Brains were removed 1 week after HI injury and infarct volumes were compared in H&E stained sections between the two groups. Results TLR-2 and TLR-3 were highly expressed in brains of P3 and P5 but not in P7 rats. The number of TLR-4 positive cells was lower in P3 and P5 compared to P7 brains (P <0.05). TLR-3 was predominately expressed in P5 pups (P <0.05). There was no significant difference in TLR-9 expression in the three age groups. There was a significant reduction in infarct volume (P?=?0.01) in poly I:C compared to saline pre-treated P5 pups. Pre-treatment with poly I:C downregulated NF-κB and upregulated IRF3 expression in P5 rat ischemic brains. Pre-treatment with poly I:C did not offer neuroprotection in P7 rat brains. Conclusion TLRs expression and function is developmentally determined. Poly I:C-induced preconditioning against ischemic injury may be mediated by modulation of TLR-3 signaling pathways. This is the first study to show that TLR-3 is expressed in the immature brain and mediates preconditioning against ischemic injury.
机译：背景我们已经表明，通过脂多糖（LPS）进行预处理将使P7大鼠的缺血性脑损伤减少90％。在P3或P5幼崽（对应于人类早产儿）中未观察到这种强大的LPS神经保护作用。 LPS是已知的Toll样受体4（TLR-4）配体。我们假设除TLR-4以外的TLR可能介导针对发育中的脑缺血性损伤的预处理。方法采用免疫染色法检测P3，P5和P7大鼠脑组织中TLR-2，TLR-3，TLR-4和TLR-9的表达。在随后的实验中，将P5大鼠随机分为TLR-3特异性激动剂，poly I：C或生理盐水治疗组。注射后48小时，单侧颈动脉结扎，然后缺氧65分钟，引起缺氧缺血（HI）损伤。 HI损伤后1周取出大脑，比较两组之间H＆E染色切片的梗塞体积。结果TLR-2和TLR-3在P3和P5脑中高表达，而在P7大鼠中不高。与P7大脑相比，P3和P5中TLR-4阳性细胞的数量较少（P <0.05）。 TLR-3主要在P5幼犬中表达（P <0.05）。在三个年龄组中，TLR-9表达没有显着差异。与盐水预处理的P5幼犬相比，poly I：C的梗死体积显着减少（P <= 0.01）。聚I：C预处理可降低P5大鼠缺血性脑中NF-κB和IRF3表达。聚I：C预处理未在P7大鼠大脑中提供神经保护作用。结论TLRs的表达和功能由发育决定。 Poly I：C诱导的针对缺血性损伤的预处理可以通过调节TLR-3信号通路来介导。这是第一个表明TLR-3在未成熟的大脑中表达并介导针对缺血性损伤的预处理的研究。

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