Neuroprotective potential of the NF-κB inhibitor peptide IKK-NBD in cerebral ischemia-reperfusion injury
Neuroprotective potential of the NF-κB inhibitor peptide IKK-NBD in cerebral ischemia-reperfusion injury
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DOI：
10.1016/j.neuint.2010.09.006
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发表时间：
2010-12-01
影响因子：
4.2
通讯作者：
Raghubir, Ram
中科院分区：
文献类型：
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作者：
Desai, Abhishek;Singh, Nilendra;Raghubir, Ram
炎症在缺血病理学中起着重要作用 NF-κ B 是一种转录因子，在炎症和细胞存活中起着至关重要的作用，但其在缺血后的确切作用仍不确定因此，我们使用中脑评估了脑室内施用高度特异性 NF-κ B 抑制肽 IKK-NBD 对大鼠短暂性局灶性脑缺血损伤的影响 动脉闭塞模型 评估缺血引起的神经功能缺损 促炎细胞因子 IL-1 β 水平的变化 血脑屏障 (BBB) 通透性 OX-42 免疫反应性变化 活性氧 (ROS) 产生和末端 dUTP 缺口末端标记 (TUNEL) 的 DNA 碎片在缺血 1 小时后再灌注 24 小时进行监测 用 40 μg IKK-NBD 或作为对照的无活性 IKK-NBD 肽预处理后 用 IKK-NBD 肽预处理显着改善脑缺血引起的神经功能缺损 通过 ELISA 对 IL-1 β 进行定量显示，IKK-NBD 肽治疗的大鼠纹状体 IL-1 β 水平显着降低 治疗还导致小胶质细胞 OX-42 染色减少，伊文思蓝染料外渗显着减少，表明 BBB 免受缺血性损伤的保护。这些结果表明，特异性 NF-κ B 抑制可淡化缺血后炎症。此外，通过 TUNEL 染色评估的 DNA 片段减少也证实了 IKK-NBD 肽的神经保护作用，因此可能是 推断 IKK-NBD 肽可减少缺血性脑损伤，这至少部分归因于缺血性损伤后炎症的减少 (C) 2010 Elsevier Ltd 保留所有权利
Inflammation plays an important role in ischemic pathology NF-kappa B is a transcription factor that has a crucial role in Inflammation and cell survival but its precise role in the ischemic aftermath is still uncertain Therefore we evaluated the effect of intracerebroventricular administration of a highly specific NF-kappa B inhibitor peptide IKK-NBD on transient focal cerebral ischemic injury in rat using middle cerebral artery occlusion model The assessment of ischemia-Induced neurological deficits alterations in the proinflammatory cytokine IL-1 beta level OX-42 immunoreactivity changes in blood-brain barrier (BBB) permeability reactive oxygen species (ROS) production and DNA fragmentation by terminal dUTP nick end labelling (TUNEL) were monitored at 24 h post reperfusion following 1 h of ischemia after pretreatment with either 40 mu g of IKK-NBD or the inactive IKK-NBD peptide which served as controlPre-treatment with IKK-NBD peptide significantly ameliorated the cerebral ischemia-Induced neurological deficits Quantification of IL-1 beta by ELISA revealed significantly reduced striatal IL-1 beta level in IKK-NBD peptide treated rats The treatment also resulted in reduced staining of microglial OX-42 and significantly reduced extravasation of Evans blue dye indicating protection of BBB from ischemic Insult These results indicate that specific NF-kappa B inhibition downplays post-ischemic inflammation Furthermore reduction in DNA fragmentation as assessed by TUNEL staining also confirms the neuroprotective effect of IKK-NBD peptide Thus It may be Inferred that IKK-NBD peptide reduces ischemic brain damage and this can at least partly be attributed to reduction in inflammation following ischemic injury (C) 2010 Elsevier Ltd All rights reserved