Adjudin protects against cerebral ischemia reperfusion injury by inhibition of neuroinflammation and blood-brain barrier disruption.
Adjudin protects against cerebral ischemia reperfusion injury by inhibition of neuroinflammation and blood-brain barrier disruption.
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Adjudin 通过抑制神经炎症和血脑屏障破坏来防止脑缺血再灌注损伤。
DOI：
10.1186/1742-2094-11-107
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发表时间：
2014-06-14
影响因子：
9.3
通讯作者：
Xia W
中科院分区：
文献类型：
--
作者：
Liu T;Zhang T;Yu H;Shen H;Xia W
由小胶质细胞激活和血脑屏障（BBB）阻断介导的神经炎症是导致缺血再灌注损伤中神经元死亡和梗死区扩散的重要因素。寻找新的分子来调节神经炎症具有重要的临床价值。我们以前已经证明，adjudin，一种已知具有抗精子生成功能的小分子化合物，通过抑制NF-κB途径减弱小胶质细胞活化。在本研究中，我们继续探索是否adjudin可以通过使用短暂的大脑中动脉闭塞（tMCAO）模型的神经保护。与溶剂组相比，再灌注后的Adjudin治疗显著降低了梗死体积和神经评分。CD 11b染色显示，adjudin显著抑制皮质和纹状体中的小胶质细胞活化，伴随着细胞因子TNF-α、IL-1β和IL-6的表达和释放的减少。同时，佐剂明显防止缺血和再灌注后的BBB破坏，如通过与媒介物组相比在大脑皮层和纹状体中IgG检测的减少所指示的。紧密连接相关蛋白ZO-1、JAM-A和Occludin的免疫荧光染色和免疫印迹也证实了这一发现，其中这些蛋白的减少可以通过调节蛋白处理来减弱。此外，adjudin明显抑制脑卒中后升高的MMP-9活性。总之，这些数据表明，adjudin保护脑缺血再灌注损伤，我们提出了一个有效的神经炎症调节剂的临床潜力。
Neuroinflammation mediated by activation of microglia and interruption of the blood-brain barrier (BBB) is an important factor that contributes to neuron death and infarct area diffusion in ischemia reperfusion injury. Finding novel molecules to regulate neuroinflammation is of significant clinical value. We have previously shown that adjudin, a small molecule compound known to possess antispermatogenic function, attenuates microglia activation by suppression of the NF-κB pathway. In this study we continued to explore whether adjudin could be neuroprotective by using the transient middle cerebral artery occlusion (tMCAO) model. Adjudin treatment after reperfusion significantly decreased the infarction volume and neuroscore compared to the vehicle group. Staining of CD11b showed that adjudin markedly inhibited microglial activation in both the cortex and the striatum, accompanied by a reduction in the expression and release of cytokines TNF-α, IL-1β and IL-6. Concomitantly, adjudin noticeably prevented BBB disruption after ischemia and reperfusion, as indicated by the reduction of IgG detection in the brain cortex and striatum versus the vehicle group. This finding was also corroborated by immunofluorescence staining and immunoblotting of tight junction-related proteins ZO-1, JAM-A and Occludin, where the reduction of these proteins could be attenuated by adjudin treatment. Moreover, adjudin obviously inhibited the elevated MMP-9 activity after stroke. Together these data demonstrate that adjudin protects against cerebral ischemia reperfusion injury, and we present an effective neuroinflammation modulator with clinical potential.
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影响因子：
6.3
作者：
Wang, Zhifei;Leng, Yan;Chuang, De-Maw
通讯作者：
Chuang, De-Maw
DOI：
10.1530/rep-10-0464
发表时间：
2011-05
期刊：
Reproduction (Cambridge, England)
影响因子：
--
作者：
Mok KW;Mruk DD;Lie PP;Lui WY;Cheng CY
通讯作者：
Cheng CY
DOI：
10.1073/pnas.87.13.5144
发表时间：
1990-07-01
影响因子：
11.1
作者：
OLIVER, CN;STARKEREED, PE;FLOYD, RA
通讯作者：
FLOYD, RA
影响因子：
6.3
作者：
Chen, JL;Zhang, CL;Chopp, M
通讯作者：
Chopp, M
影响因子：
7.3
作者：
Kirk, J;Plumb, J;McQuaid, S
通讯作者：
McQuaid, S