Löschmann P A, Eblen F, Wüllner U, Klockgether T
Department of Neurology, University of Tübingen, Federal Republic of Germany.
J Neural Transm Suppl. 1995;46:87-95.
L-glutamate itself and compounds activating glutamate receptor subtypes such as N-methyl-D-aspartate (NMDA) can produce excitotoxic lesions similar to neuronal cell damage following ischemia, traumatic brain injury or as seen in human neurodegenerative disorders. Competitive and non-competitive NMDA-receptor antagonists have neuroprotective properties in a number of in-vitro and in-vivo models for these disorders. The discovery of nitric oxide (NO) in the central nervous system (CNS) and the demonstration of the link between glutamate receptor activation and NO formation led to the hypothesis that NMDA toxicity may be mediated by NO because of its ability to promote free radical generation. Three isoforms of nitric oxide synthase (NOS) have been described, one of which is expressed constitutively in neuronal tissues (nNOS) and is perferentially inhibited by 7-nitroindazole (7-NI). One day after intrastriatal injection of NMDA, systemic pretreatment of rats with 7-NI had no effect on lesion volumes. It is concluded that formation of NO subsequent to NMDA receptor stimulation is not critically involved in excitotoxicity seen in this model.
L-谷氨酸本身以及激活谷氨酸受体亚型（如N-甲基-D-天冬氨酸，NMDA）的化合物，可产生与缺血、创伤性脑损伤后或人类神经退行性疾病中所见的神经元细胞损伤类似的兴奋毒性损伤。竞争性和非竞争性NMDA受体拮抗剂在针对这些疾病的多种体外和体内模型中具有神经保护特性。中枢神经系统（CNS）中一氧化氮（NO）的发现以及谷氨酸受体激活与NO形成之间联系的证实，引发了这样一种假说，即NMDA毒性可能由NO介导，因为其具有促进自由基生成的能力。已描述了一氧化氮合酶（NOS）的三种同工型，其中一种在神经元组织中组成性表达（nNOS），并优先被7-硝基吲唑（7-NI）抑制。在纹状体内注射NMDA一天后，用7-NI对大鼠进行全身预处理对损伤体积没有影响。得出的结论是，NMDA受体刺激后NO的形成与该模型中所见的兴奋毒性没有密切关系。
