Neurobiol Dis 2012 Jan;45 (1): 388-94. [IF:5.121]
Efficacy of the lipid-soluble iron chelator 2,2'-dipyridyl against hemorrhagic brain injury.
Wu H , Wu T , Li M , Wang J .
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA; Department of Pathology, First Clinical Hospital, Harbin Medical University, Harbin 150001, China.
哈尔滨医科大学第一临床医院病理科，约翰斯·霍普金斯大学医学院
Abstract
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 2h before ICH (pretreatment) or 6h after ICH (post-treatment) and then once daily for up to 3days. Mice in the pretreatment group were sacrificed 1 or 3days 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.
摘要：
先前的研究显示2,2'-联吡啶，一种脂溶性二价铁螯合剂，能够减轻大脑局部缺血之后的大脑损伤，且能够减轻蛛网膜下腔出血之后的大脑血管痉挛。此项研究中，我们使用12个月大的小鼠检验了2,2'-联吡啶在脑内出血之后的效能。大脑局部缺血由纹状体内注射胶原酶或者小鼠自身全血模拟。在模拟大脑局部出血之前2h腹内注射2,2'-联吡啶或者赋形剂（预处理）或者大脑局部缺血6h之后（后处理），之后每天给予2,2'-联吡啶或者赋形剂一次，持续三天。预处理组小鼠在大脑局部缺血1天或者3天的时候被处死，并检测铁含量，神经元死亡，氧化应激，微神经胶质/或者星状细胞活性，中性粒细胞渗出，和白质损伤。后处理组小鼠在第3天检测大脑损伤面积和水肿，及在大脑局部缺血的第1天，第3天和第28天检测神经缺陷。预处理组中，2,2'-联吡啶减少了铁的积累和神经元死亡，减低了活性氧化产物的产量，在不影响星状细胞或中性粒细胞渗出的情况下减低了微神经胶质的活性，并减低了白质损伤。后处理组2,2'-联吡啶减少了大脑损伤面积和水肿，并改善了神经功能。这些结果提示脂溶性的二价铁螯合剂2,2'-联吡啶在大脑局部缺血之后能够减少大脑损伤，并且改善神经功能预后。
