Attenuation of intracerebral hemorrhage and thrombin-induced brain edema by overexpression of interleukin-1 receptor antagonist
Attenuation of intracerebral hemorrhage and thrombin-induced brain edema by overexpression of interleukin-1 receptor antagonist
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DOI：
10.3171/jns.2001.95.4.0680
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发表时间：
2001-10-01
影响因子：
4.1
通讯作者：
Keep, RF
中科院分区：
文献类型：
--
作者：
Masada, T;Hua, Y;Keep, RF
Object.腺病毒介导的白细胞介素1受体拮抗剂（IL-1 ra）过表达减轻局灶性脑缺血后的炎症反应和脑损伤。最近，脑出血（ICH）后的炎症反应被确定。在这项研究中，作者检验了IL-1 ra过表达减少ICH后脑损伤（特别是水肿形成）的假设。将表达IL-1 ra的腺病毒（Ad.RSVIL-1 ra）或LacZ、对照蛋白（Ad.RSVlacZ）或盐水注射到大鼠左侧脑室。在病毒注射后第5天，将100穆尔自体血或5 U凝血酶输注到右侧基底神经节中。分别于24 h和72 h处死大鼠，测定脑含水量和脑离子含量。凝血酶处理的大鼠在24小时后处死，用于水肿测量和通过髓过氧化物酶（MPO）测定评估多形核白细胞（PMNL）浸润，以及组织学评价。与生理盐水处理和Ad. RSVlacZ转导的对照组相比，Ad.RSVIL-1 ra转导的大鼠在ICH后3天同侧基底神经节水肿显著减轻（81.5 +/- 0.3%，而对照动物为83.4 +/- 0.4%和83.3 +/- 0.5%）。在Ad.RSVIL-1 ra处理的大鼠中，凝血酶诱导的脑水肿也减少了（81.3 +/- 0.4%，而对照大鼠为83.2 +/- 0.4%和82.5 +/- 0.4%）。凝血酶诱导水肿的减少与PMNL浸润基底节的减少相关，通过MPO测定（减少49%）和组织学检查评估。使用腺病毒载体过表达IL-1 ra可减轻脑出血后脑水肿形成和凝血酶诱导的脑内炎症用IL-1 ra减少ICH诱导的水肿可能是由于凝血酶诱导的脑炎症减少。
Object. Adenovirus-mediated overexpression of interleukin-1 receptor antagonist (IL-1ra) attenuates the inflammatory reaction and brain injury that follows focal cerebral ischemia. Recently, an inflammatory reaction after intracerebral hemorrhage (ICH) was identified. In this study the authors examine the hypothesis that overexpression of IL-1ra reduces brain injury (specifically edema formation) after ICH.Methods. Adenoviruses expressing IL-1ra (Ad.RSVIL-1ra) or LacZ, a control protein (Ad.RSVlacZ), or saline were injected into the left lateral cerebral ventricle in rats. On the 5th day after virus injection, 100 mul of autologous blood or 5 U thrombin was infused into the right basal ganglia. Rats with ICH were killed 24 or 72 hours later for measurement of brain water and ion content. Thrombin-treated rats were killed 24 hours later for edema measurements and an assessment of polymorphonuclear leukocyte (PMNL) infiltration by myeloperoxidase (MPO) assay, as well as histological evaluation. Compared with saline-treated and Ad.RSVlacZ-transduced controls, Ad.RSVIL-1ra-transduced rats had significantly attenuated edema in the ipsilateral basal ganglia 3 days after ICH (81.5 +/- 0.3% compared with 83.4 +/- 0.4% and 83.3 +/- 0.5% in control animals). Thrombin-induced brain edema was also reduced in Ad.RSVIL-1ra-treated rats (81.3 +/- 0.4% compared with 83.2 +/- 0.4% and 82.5 +/- 0.4% in control rats). The reduction in thrombin-induced edema was associated with a reduction in PMNL infiltration into the basal ganglia, as assessed by MPO assay (49% reduction) and histological examination.Conclusions. Overexpression of IL-1ra by using an adenovirus vector attenuated brain edema formation and thrombin-induced intracerebral inflammation following ICH. The reduction in ICH-induced edema with IL-1ra may result from reduction of thrombin-induced brain inflammation.