Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products
Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products
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DOI：
10.3171/jns.2002.96.2.0287
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发表时间：
2002-02-01
影响因子：
4.1
通讯作者：
Hoff, JT
中科院分区：
文献类型：
--
作者：
Huang, FP;Xi, GH;Hoff, JT
Object.脑出血（ICH）后脑水肿形成的机制尚未完全阐明。作者发现，红细胞溶解在ICH后水肿发展中起重要作用。在目前的研究中，他们试图确定血红蛋白的降解产物是否会引起脑水肿。在立体定向引导下，将血红蛋白、氯化高铁血红素、胆红素或FeCl 2注入Sprague-Dawley大鼠的右侧基底神经节。24小时后处死动物，测定脑水和离子含量。采用免疫印迹法和免疫组化法检测血红素氧合酶-1（HO-1）的表达。HO抑制剂锡原卟啉（SnPP）和铁螯合剂去铁胺对血红蛋白诱导的脑水肿的影响也进行了检查。脑内输注血红蛋白、氯化血红素、胆红素或FeCl 2在24小时引起脑含水量增加。HO-1在血红蛋白输注和SnPP减弱的血红蛋白诱导的水肿的HO抑制后上调。腹腔注射去铁胺500 mg/kg可减轻血红蛋白引起的脑水肿。血红蛋白至少部分通过其降解产物引起脑水肿。限制血红蛋白降解结合使用铁螯合剂可能是限制ICH后脑水肿的一种新的治疗方法。
Object. The mechanisms involved in brain edema formation following intracerebral hemorrhage (ICH) have not been fully elucidated. The authors have found that red blood cell lysis plays an important role in edema development after ICH. In the present study, they sought to determine whether degradation products of hemoglobin cause brain edema.Methods. Hemoglobin, hemin, bilirubin, or FeCl2 were infused with stereotactic guidance into the right basal ganglia of Sprague-Dawley rats. The animals were killed 24 hours later to determine brain water and ion contents. Western blot analysis and immunohistochemistry were applied for heme oxygenase-1 (HO-1) measurement. The effects of an HO inhibitor, tin-protoporphyrin (SnPP), and the iron chelator deferoxamine, on hemoglobin-induced brain edema were also examined.Intracerebral infusion of hemoglobin, hemin, bilirubin, or FeCl2 caused an increase in brain water content at 24 hours. The HO-1 was upregulated after hemoglobin infusion and HO inhibition by SnPP-attenuated hemoglobin-induced edema. Brain edema induced by hemoglobin was also attenuated by the intraperitoneal injection of 500 mg/kg deferoxamine.Conclusions. Hemoglobin causes brain edema, at least in part, through its degradation products. Limiting hemoglobin degradation coupled with the use of iron chelators may be a novel therapeutic approach to limit brain edema after ICH.