NEUROPROTECTIVE ACTIVITY OF GLUTAMATE-RECEPTOR ANTAGONISTS AGAINST SOMAN-INDUCED HIPPOCAMPAL DAMAGE - QUANTIFICATION WITH AN OMEGA-3 SITE LIGAND
NEUROPROTECTIVE ACTIVITY OF GLUTAMATE-RECEPTOR ANTAGONISTS AGAINST SOMAN-INDUCED HIPPOCAMPAL DAMAGE - QUANTIFICATION WITH AN OMEGA-3 SITE LIGAND
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DOI：
10.1016/0006-8993(93)91270-3
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发表时间：
1993-08-06
期刊：
影响因子：
2.9
通讯作者：
BLANCHET, G
中科院分区：
文献类型：
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作者：
LALLEMENT, G;DELAMANCHE, IS;BLANCHET, G
以往的研究表明，omega3(外周型苯二氮卓)结合位点密度的测量在中枢神经系统神经组织损伤的定位和定量方面具有广泛的适用性。在本研究的第一步中，验证了这种方法在评估梭曼诱导的脑损伤方面的适用性。放射自显影研究显示，在梭曼攻击后2天，惊厥大鼠几个脑区的omega3位点密度显著增加。这些增加与梭曼引起的神经病理改变的方式和幅度密切相关，并与受损组织的胶质细胞反应和巨噬细胞侵袭密切相关。然后，我们使用这个标记物在小鼠海马区评估了NBQX和TCP对梭曼诱导的脑损伤的神经保护作用，NBQX和TCP分别是非NMDA和NMDA谷氨酸能受体的拮抗剂。梭曼前5min注射NBQX 20或40 mg/kg可完全阻止神经元的损伤。相比之下，在梭曼前5min给药1 mg/kg，1h后再给药，则有较好的神经保护作用。这些结果表明，NBQX和TCP对梭曼所致的脑损伤均具有良好的神经保护作用。鉴于已知梭曼致痫的神经病理与癫痫发作密切相关，本文结合非NMDA受体和NMDA受体在梭曼致痫的发生和维持中的作用，讨论了NBQX和TCP2的神经保护作用。
Previous investigations have indicated that the measurement of omega3 (peripheral-type benzodiazepine) binding site densities could be of widespread applicability in the localization and quantification of neural tissue damage in the central nervous system. In the first step of the present study, the suitability of this approach for the assessment of soman-induced brain damage was validated. Autoradiographic study revealed marked increases of omega3 site densities in several brain areas of convulsing rats 2 days after soman challenge. These increases were well-correlated with the pattern and the amplitude of neuropathological alterations due to soman and closely related to both glial reaction and macrophage invasion of the lesioned tissues. We then used this marker to assess, in mouse hippocampus, the neuroprotective activity against soman-induced brain damage of NBQX and TCP which are respective antagonists of non-NMDA and NMDA glutamatergic receptors. Injection of NBQX at 20 or 40 mg/kg 5 min prior to soman totally prevented the neuronal damage. Comparatively, TCP had neuroprotective efficacy when administered at 1 mg/kg 5 min prior to soman followed by a reinjection 1 h after. These results demonstrate that both NBQX and TCP afford a satisfactory neuroprotection against soman-induced brain damage. Since it is known that the neuropathology due to soman is closely seizure-related, the neuroprotective activities of NBQX and TCP are discussed in relation with the respective roles of non-NMDA and NMDA receptors in the onset and maintenance of soman-induced seizures.