Pro-inflammatory interferon gamma signaling is directly associated with stroke induced neurodegeneration.
Pro-inflammatory interferon gamma signaling is directly associated with stroke induced neurodegeneration.
复制标题
DOI：
10.1007/s11481-014-9560-2
复制
发表时间：
2014-12
影响因子：
6.2
通讯作者：
Pennypacker, Keith R.
中科院分区：
文献类型：
--
作者：
Seifert, Hilary A.;Collier, Lisa A.;Chapman, Cortney B.;Benkovic, Stanley A.;Willing, Alison E.;Pennypacker, Keith R.
对中风的延迟免疫反应是导致在最初的缺血事件后继续发生的神经损伤增加的原因。这种延迟的免疫反应与脾有关，因为在大脑中动脉闭塞(MCAO)之前切除脾具有神经保护作用。干扰素γ与脾反应有关，可增强大脑中动脉阻塞后的神经损伤。干扰素γ激活炎性趋化因子干扰素诱导蛋白10(IP-10)的表达。本研究旨在探讨干扰素γ信号在大脑中动脉阻塞后炎症反应中的作用。脑缺血后IP-10在脑和脾组织的表达增加。脾切除可抑制大脑中IP-10的升高，而重组干扰素γ可使大鼠脑内IP-10的水平恢复到脑缺血后的水平。对大脑中动脉阻塞治疗的大鼠全身注射干扰素γ中和抗体可减少脑梗塞体积和脑内IP-10水平。与接受同型对照抗体的动物相比，接受干扰素γ抗体治疗的动物大脑中受损的T细胞浸润减少。此外，用脾切除或干扰素γ中和抗体抑制干扰素γ信号转导可阻断IP-10的表达，减少大脑中动脉阻塞后的神经变性。靶向卒中后的这种促炎途径可能是一种有前途的卒中治疗方法。
The delayed immune response to stroke is responsible for the increased neural injury that continues to occur after the initial ischemic event. This delayed immune response has been linked to the spleen, as splenectomy prior to middle cerebral artery occlusion (MCAO) is neuroprotective. Interferon gamma (IFNγ) is linked to the splenic response, which enhances neural injury following MCAO. IFNγ activates the expression of the inflammatory chemokine interferon-inducible protein 10 (IP-10). This study was designed to determine the role of IFNγ signaling in the inflammatory response following MCAO. Expression of IP-10 increased in the brain and the spleen following MCAO. Splenectomy inhibited the increase of IP-10 in the brain post-MCAO, while recombinant IFNγ administration to splenectomized rats returned IP-10 levels in the brain to levels found in rats after MCAO only. Systemic administration of an IFNγ neutralizing antibody to MCAO-treated rats reduced infarct volume and IP-10 levels in the brain. T cell infiltration was reduced in the MCAO-damaged brains of IFNγ antibody-treated animals relative to those that received isotype control antibodies. Additionally, inhibiting IFNγ signaling with splenectomy or an IFNγ neutralizing antibody blocked the induction of IP-10 expression and decreased neurodegeneration following MCAO. Targeting this pro-inflammatory pathway following stroke could be a promising stroke therapeutic.
登录
查看更多内容
影响因子：
14.5
作者：
Lee, Soon-Tae;Chu, Kon;Roh, Jae-Kyu
通讯作者：
Roh, Jae-Kyu
影响因子：
2.1
作者：
Ajmo, Craig T., Jr.;Vernon, Dionne O. L.;Cuevas, Javier
通讯作者：
Cuevas, Javier
影响因子：
2.9
作者：
Duckworth, EAM;Butler, TL;Pennypacker, KR
通讯作者：
Pennypacker, KR
影响因子：
82.9
作者：
Liesz, Arthur;Suri-Payer, Elisabeth;Veltkamp, Roland
通讯作者：
Veltkamp, Roland
影响因子：
4.2
作者：
Hall, A. A.;Guyer, A. G.;Leonardo, C. C.;Ajmo, C. T., Jr.;Collier, L. A.;Willing, A. E.;Pennypacker, K. R.
通讯作者：
Pennypacker, K. R.