Sensitive indicators of injury reveal hippocampal damage in C57BL/6J mice treated with kainic acid in the absence of tonic-clonic seizures
Sensitive indicators of injury reveal hippocampal damage in C57BL/6J mice treated with kainic acid in the absence of tonic-clonic seizures
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DOI：
10.1016/j.brainres.2004.07.021
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发表时间：
2004-10-22
期刊：
影响因子：
2.9
通讯作者：
Miller, DB
中科院分区：
文献类型：
--
作者：
Benkovic, SA;O'Callaghan, JP;Miller, DB
神经损伤的敏感指数用于评估红藻氨酸（KA）诱导的成年C57 BL/6 J小鼠（4个月）海马损伤的时程，该品系先前报道对红藻氨酸诱导的神经毒性具有抗性。小鼠全身注射生理盐水或红藻氨酸盐，对癫痫发作严重程度进行评分（拉辛量表），并存活12小时、1天、3天或7天，然后使用组织学或生化终点评价它们的神经病理学变化。大多数红藻氨酸治疗的小鼠表现出有限的癫痫发作活动（阶段1），然而，铜银和Fluoro-Jade B染色显示治疗后12小时的显着损害。免疫组化和免疫测定的胶质细胞酸性蛋白和凝集素染色显示了强烈的治疗诱导的反应性胶质增生和小胶质细胞活化。免疫球蛋白G的免疫染色显示红藻氨酸诱导的血脑屏障的突破。尼氏染色和苏木精染色提供的关于神经元损伤的信息很少，但揭示了浸润锥体层的非常驻细胞的身份。我们的数据表明，敏感指标的神经损伤评估在一个时间过程中，近端和远端的治疗，是必要的，以揭示神经病理变化的全部程度，可能被低估了传统的组织学染色。本文报道的神经病理学指标的电池揭示了C57 BL/6 J小鼠对红藻氨酸引起的兴奋性毒性神经损伤敏感，在没有强直-阵挛性癫痫发作的情况下。由爱思唯尔公司出版
Sensitive indices of neural injury were used to evaluate the time course of kainic acid (KA)-induced hippocampal damage in adult C57BL/6J mice (4 months), a strain previously reported to be resistant to kainate-induced neurotoxicity. Mice were injected systemically with saline or kainate, scored for seizure severity (Racine scale), and allowed to survive 12 h, one, three, or seven days following which they were evaluated for neuropathological changes using histological or biochemical endpoints. Most kainate-treated mice exhibited limited seizure activity (stage 1); however, cupric-silver and Fluoro-Jade B stains revealed significant damage by 12 h post-treatment. Immunohistochemistry and immunoassay of glial fibrillary acidic protein and lectin staining revealed a strong treatment-induced reactive gliosis and microglial activation. Immunostaining for immunoglobulin G revealed a kainate-induced breach in the blood-brain barrier. Nissl and hematoxylin stains provided little information regarding neuronal damage, but revealed the identity of non-resident cells which infiltrated the pyramidal layer. Our data suggest sensitive indicators of neural injury evaluated over a time course, both proximal and distal to treatment, are necessary to reveal the full extent of neuropathological changes which may be underestimated by traditional histological stains. The battery of neuropathological indices reported here reveals the C57BL/6J mouse is sensitive to excitotoxic neural damage caused by kainic acid, in the absence of tonic-clonic seizures. Published by Elsevier B.V.