ACUTE EFFECTS OF IRRADIATION ON THE RAT-BRAIN - PROTECTION BY GLUTAMATE BLOCKADE
ACUTE EFFECTS OF IRRADIATION ON THE RAT-BRAIN - PROTECTION BY GLUTAMATE BLOCKADE
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DOI：
10.1016/0014-2999(95)00006-7
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发表时间：
1995-03-24
影响因子：
5
通讯作者：
STUTZMANN, JM
中科院分区：
文献类型：
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作者：
ALAOUI, F;PRATT, J;STUTZMANN, JM
Riluzole（2-氨基-6-三氟乙氧基苯并噻唑），地佐环平（MK-801;（+）-5-甲基-10，11-二氢-5H-二苯并（a，d）-环庚烯-5，10-亚胺马来酸盐）和拉莫三嗪（3，5-二氨基-6-（2，3-二氯苯基）-1，2-三嗪），据报道具有神经保护作用的药剂，以及WR 2721在接受钴60源2.5戈瑞（戈伊）照射的15日龄大鼠中评价了放射保护剂（S-2-（3-氨基丙基氨基）-乙基硫代磷酸）。照射后20分钟，腹膜内注射利鲁唑（0.5-8 mg/kg）、地佐环平（0.1-1 mg/kg）、拉莫三嗪（25 mg/kg）、WR 2721（75 mg/kg）或载体。照射后6小时，行为和组织学评价显示，暴露于2.5戈伊引起运动不足、蹒跚步态和嗜睡，与4 mg/kg腹腔注射利鲁唑相比，上述情况显著减少。从1 mg/kg i. p.剂量开始，还观察到对齿状回神经元的剂量依赖性保护。地佐环平引起行为改变，但显着减少神经元损伤。拉莫三嗪显着增加神经元损伤，而WR 2721赋予没有保护。总之，两个阻断剂的amatergic神经传递赋予显着的保护作用，对脑损伤所造成的电离辐射时，管理后的曝光。
Riluzole (2-amino-6-trifluorothethoxy benzothiazole), dizocilpine (MK-801; (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclohepten-5,10-imine maleate), and lamotrigine (3,5-diamino-6-(2,3-dichlorophenyl)-1,2-triazine), agents reported to have neuroprotective actions, and WR2721 (S-2-(3-aminopropylamino)-ethylphosphorothioic acid), a radioprotector, were evaluated in 15-day-old rats that underwent a 2.5 Gray (Gy) irradiation from a cobalt 60 source. 20 min after irradiation, riluzole (0.5-8 mg/kg), dizocilpine (0.1-1 mg/kg), lamotrigine (25 mg/kg), WR 2721 (75 mg/kg) or vehicle, were injected intraperitoneally. 6 h after irradiation, behavioural and histological evaluations revealed that exposure to 2.5 Gy caused hypolocomotion, stumbling gait and somnolence, which was significantly reduced, from the dose of 4 mg/kg i.p. of riluzole. A dose-dependent protection of neurones in the dentate gyrus, starting from the dose of 1 mg/kg i.p. was also seen. Dizocilpine caused behavioural modifications but significantly reduced neuronal damage. Lamotrigine significantly increased neuronal damage while WR 2721 conferred no protection. In conclusion, two blockers of glutamatergic neurotransmission conferred significant protection against brain damage caused by ionizing irradiation when administered subsequent to exposure.