Efficacy of the lipid-soluble iron chelator 2,2'-dipyridyl against hemorrhagic brain injury.
Efficacy of the lipid-soluble iron chelator 2,2'-dipyridyl against hemorrhagic brain injury.
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DOI：
10.1016/j.nbd.2011.08.028
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发表时间：
2012-01
影响因子：
6.1
通讯作者：
Wang, Jian
中科院分区：
文献类型：
--
作者：
Wu, He;Wu, Tao;Li, Mingchang;Wang, Jian
已有研究表明，脂溶性铁络合剂2，2‘-联吡啶可以减轻脑缺血后的脑损伤，减少蛛网膜下腔出血后的脑血管痉挛。在这项研究中，我们研究了2，2‘-联吡啶对12月龄小鼠脑出血后的疗效。脑出血模型采用纹状体内注射胶原酶或自体全血的方法。脑出血前2小时(治疗前)或脑出血后6小时(治疗后)分别给予2，2‘-联吡啶或2，2’-联吡啶或赋形剂，每日1次，连续3天。预处理组于脑出血后1~3d处死小鼠，检测铁沉积、神经元死亡、氧化应激、小胶质细胞/星形胶质细胞活化、中性粒细胞浸润和脑白质损伤。后处理组小鼠在脑出血后第3天进行脑损伤体积和脑水肿检查，在第1、3和28天进行神经功能缺失检查。2，2‘-联吡啶可减少铁蓄积和神经元死亡，减少活性氧的产生，减少小胶质细胞的活化，而不影响星形胶质细胞或中性粒细胞的浸润，并减轻脑白质的损伤。治疗后可减少脑损伤体积和脑水肿，改善神经功能。这些结果表明，脂溶性铁络合剂2，2‘-联吡啶可以减轻脑出血后的脑损伤，改善功能预后。
Previous studies have indicated that 2,2′-dipyridyl, a lipid-soluble ferrous iron chelator, can reduce brain injury after cerebral ischemia and reduce cerebral vasospasm after subarachnoid hemorrhage. In this study, we examined the efficacy of 2,2′-dipyridyl after intracerebral hemorrhage (ICH) in 12-month-old mice. ICH was modeled by intrastriatal injection of collagenase or autologous whole blood. 2,2′-Dipyridyl or vehicle was administered intraperitoneally 2 h before ICH (pretreatment) or 6 h after ICH (post-treatment) and then once daily for up to 3 days. Mice in the pretreatment group were sacrificed 1 or 3 days after ICH and examined for iron deposition, neuronal death, oxidative stress, microglial/astrocyte activation, neutrophil infiltration, and white matter damage. Mice in the post-treatment group were examined for brain lesion volume and edema on day 3 and for neurologic deficits on days 1, 3, and 28 after ICH. Pretreatment with 2,2′-dipyridyl decreased iron accumulation and neuronal death, attenuated production of reactive oxygen species, reduced microglial activation without affecting astrocytes or neutrophil infiltration, and attenuated white matter damage. Post-treatment reduced brain lesion volume and edema and improved neurologic function. These results indicate that the lipid-soluble ferrous iron chelator 2,2′-dipyridyl can reduce brain injury and improve functional outcome after ICH.
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