The effects of dexmedetomidine on perinatal excitotoxic brain injury are mediated by the α2A-adrenoceptor subtype
The effects of dexmedetomidine on perinatal excitotoxic brain injury are mediated by the α2A-adrenoceptor subtype
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DOI：
10.1213/01.ane.0000194301.79118.e9
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发表时间：
2006-02-01
影响因子：
5.7
通讯作者：
Gressens, P
中科院分区：
文献类型：
--
作者：
Paris, A;Mantz, J;Gressens, P
我们在缺乏单个α（2）-肾上腺素受体亚型的小鼠中进行了当前研究，以阐明α（2）-肾上腺素受体亚型对围产期兴奋性脑损伤模型中右美托咪定神经保护特性的贡献。在出生后第5天，将野生型小鼠和缺乏α（2A）-肾上腺素受体（α（2A）-KO）或α（2C）-肾上腺素受体亚型（α（2C）-KO）的小鼠随机分配接受右美托咪定（3 μ g/ kg）或磷酸盐缓冲盐水腹腔内给药。腹膜内注射后30分钟，脑内注射多巴胺能激动剂鹅膏蕈氨酸（10 μ g），产生经皮质坏死和白色物质损伤，模拟围产期人类缺氧样损伤。在出生后第10天通过组织病理学检查对病变进行定量。右美托咪定使野生型小鼠和α（2C）-KO小鼠皮质中的平均病变大小分别降低44%和49%。用右美托咪定预处理后，鹅膏蕈氨酸诱导的白色病变减少了71%（野生型小鼠）和75%（α（2C）-KO小鼠）。相比之下，在α（2C）-KO小鼠中，右美托咪定不能防止皮质兴奋性毒性损伤，并且白色病变更加明显（平均病变尺寸增加82%）。右美托咪定在围产期兴奋性毒性脑损伤模型中提供有效的神经保护作用。这种作用在α（2A）-KO小鼠中完全消除，表明神经保护作用是通过α（2A）-肾上腺素受体亚型介导的。
We performed the current study in mice lacking individual alpha(2)-adrenoceptor subtypes to elucidate the contribution of alpha(2)-adrenoceptor subtypes to the neuroprotective properties of dexmedetomidine in a model of perinatal excitotoxic brain injury. On postnatal Day 5, wild-type mice and mice lacking alpha(2A)-adrenoceptor (alpha(2A)-KO) or alpha(2C)-adrenoceptor subtypes (alpha(2C)-KO) were randomly assigned to receive dexmedetomidine (3 mu g/ kg) or phosphate-buffered saline intraperitoneally. Thirty minutes after the intraperitoneal injection, the glutamatergic agonist ibotenate (10 mu g) was intracerebrally injected, producing transcortical necrosis and white matter lesions that mimic perinatal human hypoxic-like lesions. Quantification of the lesions was performed on postnatal Day 10 by histopathologic examination. Dexmedetomidine reduced mean lesion size in the cortex of wild-type mice and alpha(2C)-KO mice by 44% and 49%, respectively. Ibotenate-induced white matter lesions were reduced by 71% (wild-type mice) and 75% (alpha(2C)-KO mice) after pretreatment with dexmedetomidine. In contrast, in alpha(2C)-KO mice, dexmedetomidine did not protect against the cortical excitotoxic insult, and white matter lesions were even more pronounced (82% increase of mean lesion size). Dexmedetomidine provides potent neuroprotection in a model of perinatal excitotoxic brain damage. This effect was completely abolished in alpha(2A)-KO mice, suggesting that the neuroprotective effect is mediated via the alpha(2A)-adrenoceptor subtype.