A translocator protein 18 kDa agonist protects against cerebral ischemia/reperfusion injury.
A translocator protein 18 kDa agonist protects against cerebral ischemia/reperfusion injury.
复制标题
易位蛋白 18 kDa 激动剂可预防脑缺血/再灌注损伤
DOI：
10.1186/s12974-017-0921-7
复制
发表时间：
2017-07-28
影响因子：
9.3
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Li HD;Li M;Shi E;Jin WN;Wood K;Gonzales R;Liu Q
背景脑缺血是导致死亡和残疾的主要原因，治疗选择有限。虽然炎症和免疫反应参与了缺血性脑损伤，但缺血后神经炎症的分子调节因子仍有待确定。主要定位于线粒体外膜的转运蛋白18 kDa（TSPO）在炎症状态下主要在中枢神经系统内的神经胶质中表达。本研究探讨了TSPO激动剂，etifoxine，对神经炎症和脑损伤后缺血/reperfusion.MethodsWe使用的小鼠模型大脑中动脉闭塞（MCAO）检查治疗潜力和神经保护机制etifoxine.ResultsTSPO上调Iba 1+或CD 11b + CD 45 int细胞从小鼠进行MCAO和再灌注。Etifoxine显着减弱神经功能缺损和梗死体积后MCAO和再灌注。在经历30、60或90分钟MCAO的小鼠中，衰减明显。艾提伏辛减少缺血性脑中促炎因子的产生。此外，艾提伏辛治疗导致小胶质细胞白细胞介素-1 β、白细胞介素-6、肿瘤坏死因子-α和诱导型一氧化氮合酶的表达降低。值得注意的是，艾提伏辛对脑梗死的好处是消融在小鼠耗尽的小胶质细胞使用集落刺激因子1受体inhibitors.ConclusionsThese研究结果表明，TSPO激动剂，艾提伏辛，减少神经炎症和缺血/再灌注后的脑损伤。靶向TSPO的治疗潜力需要进一步研究缺血性卒中。
BackgroundCerebral ischemia is a leading cause of death and disability with limited treatment options. Although inflammatory and immune responses participate in ischemic brain injury, the molecular regulators of neuroinflammation after ischemia remain to be defined. Translocator protein 18 kDa (TSPO) mainly localized to the mitochondrial outer membrane is predominantly expressed in glia within the central nervous system during inflammatory conditions. This study investigated the effect of a TSPO agonist, etifoxine, on neuroinflammation and brain injury after ischemia/reperfusion.MethodsWe used a mouse model of middle cerebral artery occlusion (MCAO) to examine the therapeutic potential and mechanisms of neuroprotection by etifoxine.ResultsTSPO was upregulated in Iba1+or CD11b+CD45intcells from mice subjected to MCAO and reperfusion. Etifoxine significantly attenuated neurodeficits and infarct volume after MCAO and reperfusion. The attenuation was pronounced in mice subjected to 30, 60, or 90 min MCAO. Etifoxine reduced production of pro-inflammatory factors in the ischemic brain. In addition, etifoxine treatment led to decreased expression of interleukin-1β, interleukin-6, tumor necrosis factor-α, and inducible nitric oxide synthase by microglia. Notably, the benefit of etifoxine against brain infarction was ablated in mice depleted of microglia using a colony-stimulating factor 1 receptor inhibitor.ConclusionsThese findings indicate that the TSPO agonist, etifoxine, reduces neuroinflammation and brain injury after ischemia/reperfusion. The therapeutic potential of targeting TSPO requires further investigations in ischemic stroke.
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DOI：
10.1523/jneurosci.2102-11.2011
发表时间：
2011-09-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Faustino JV;Wang X;Johnson CE;Klibanov A;Derugin N;Wendland MF;Vexler ZS
通讯作者：
Vexler ZS
神经干细胞维持自然杀伤细胞的作用，从而控制大脑炎症的恢复
影响因子：
25
作者：
Liu Q;Sanai N;Jin WN;La Cava A;Van Kaer L;Shi FD
通讯作者：
Shi FD
影响因子：
3.7
作者：
Mendu SK;Bhandage A;Jin Z;Birnir B
通讯作者：
Birnir B
影响因子：
4.7
作者：
Frechou, Magalie;Zhang, Shaodong;Guennoun, Rachida
通讯作者：
Guennoun, Rachida
DOI：
10.1111/bpa.12196
发表时间：
2014-11
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
--
作者：
Liu GJ;Middleton RJ;Hatty CR;Kam WW;Chan R;Pham T;Harrison-Brown M;Dodson E;Veale K;Banati RB
通讯作者：
Banati RB