A TSPO ligand attenuates brain injury after intracerebral hemorrhage.
A TSPO ligand attenuates brain injury after intracerebral hemorrhage.
复制标题
TSPO配体减轻脑出血后的脑损伤
DOI：
10.1096/fj.201601377rr
复制
发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Li M;Ren H;Sheth KN;Shi FD;Liu Q
脑出血（Intracerebral hemorrhage，ICH）是一种严重的疾病，目前尚无有效的治疗方法。脑出血后，白细胞的立即浸润和小胶质细胞的活化伴随着18-kDa转运蛋白（TSPO）的快速上调。TSPO配体在CNS损伤模型中显示出抗炎和神经保护特性。在这项研究中，我们确定了TSPO配体艾提伏辛对2种ICH小鼠模型脑损伤和炎症的影响。TSPO在ICH患者脑内的Iba 1+细胞和胶原酶诱导的ICH小鼠的CD 11b + CD 45 int细胞中上调。通过注射自体血或胶原酶诱导ICH后，艾提伏辛显著减少神经缺损和血肿周围脑水肿。在胶原酶诱导的ICH小鼠中，艾提伏辛的保护作用与减少白细胞浸润到脑中以及小胶质细胞产生IL-6和TNF-α有关。艾提伏辛改善血脑屏障的完整性，减少细胞死亡。值得注意的是，通过使用集落刺激因子1受体抑制剂消除了小胶质细胞耗竭小鼠中艾提伏辛的保护作用。这些结果表明，TSPO配体艾提伏辛减轻ICH后的脑损伤和炎症。TSPO可能是一个可行的治疗靶点，需要在ICH中进行进一步研究。Li，M.，Ren，H.，Sheth，K. N.，施，F.- D、刘，智-地TSPO配体减轻脑出血后的脑损伤
Intracerebral hemorrhage (ICH) is a devastating disease without effective treatment. After ICH, the immediate infiltration of leukocytes and activation of microglia are accompanied by a rapid up-regulation of the 18-kDa translocator protein (TSPO). TSPO ligands have shown anti-inflammatory and neuroprotective properties in models of CNS injury. In this study, we determined the impact of a TSPO ligand, etifoxine, on brain injury and inflammation in 2 mouse models of ICH. TSPO was up-regulated in Iba1+ cells from brains of patients with ICH and in CD11b+CD45int cells from mice subjected to collagenase-induced ICH. Etifoxine significantly reduced neurodeficits and perihematomal brain edema after ICH induction by injection of either autologous blood or collagenase. In collagenase-induced ICH mice, the protection of etifoxine was associated with reduced leukocyte infiltration into the brain and microglial production of IL-6 and TNF-α. Etifoxine improved blood–brain barrier integrity and diminished cell death. Notably, the protective effect of etifoxine was abolished in mice depleted of microglia by using a colony-stimulating factor 1 receptor inhibitor. These results indicate that the TSPO ligand etifoxine attenuates brain injury and inflammation after ICH. TSPO may be a viable therapeutic target that requires further investigations in ICH.—Li, M., Ren, H., Sheth, K. N., Shi, F.-D., Liu, Q. A TSPO ligand attenuates brain injury after intracerebral hemorrhage.