PRODUCTION OF LIMBIC MOTOR SEIZURES AND BRAIN-DAMAGE BY SYSTEMIC AND INTRACEREBRAL INJECTIONS OF PARAQUAT IN RATS
PRODUCTION OF LIMBIC MOTOR SEIZURES AND BRAIN-DAMAGE BY SYSTEMIC AND INTRACEREBRAL INJECTIONS OF PARAQUAT IN RATS
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DOI：
10.1111/j.1600-0773.1992.tb00575.x
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发表时间：
1992-12-01
期刊：
影响因子：
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通讯作者：
STEPHENSON, JD
中科院分区：
文献类型：
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作者：
BAGETTA, G;CORASANITI, MT;STEPHENSON, JD
对大鼠全身和海马内注射百草枯二氯化物（1，1 '-二甲基4，4'-联吡啶二氯化物）的行为和神经病理学影响进行了研究。将百草枯（0.1-1.0 μ mol）注入背侧海马，在注射后几分钟内产生边缘系统运动性癫痫发作，随后在24小时时在CA 1和CA 3锥体细胞层、梨状皮质、齿状颗粒细胞层和筋膜门中出现神经元损伤（n=9只大鼠）。较小剂量的百草枯（10 nmol）无效。海马内注射百草枯（1 μ mol）的影响可通过与阿托品（50 nmol; n=6只大鼠）一起给药或在MK 801（0.3 mg.kg-1腹腔注射）后60分钟给药来预防。全身注射百草枯（20-100 mg.kg-1）也使15只动物中的10只出现前肢阵挛和直立。24小时后，在其中9只大鼠中发现神经元细胞死亡，仅限于梨状皮质，这是百草枯浓度最高的大脑区域。阿托品（150 mg.kg-1，60 min前腹腔注射）完全阻止了运动性癫痫发作，但在6只受试动物中仍有2只发生细胞死亡。总之，全身和海马内注射百草枯产生的行为兴奋伴随24小时后脑损伤和拮抗剂的研究表明参与毒蕈碱和NMDA受体的神经毒性机制。
The behavioural and neuropathological effects of both systemic and intrahippocampal injections of paraquat dichloride (1,1'-dimethyl 4,4'-bipyridinium dichloride) were studied in rats. Paraquat (0.1-1.0 mumol) injected into the dorsal hippocampus, produced limbic motor seizures within a few minutes of injection followed by neuronal damage in the CA1 and CA3 pyramidal cell layers, pyriform cortex, dentate granule cell layer and in the hilus fascia dentata at 24 hr (n=9 rats). A smaller dose of paraquat (10 nmol) was ineffective. The effects of intrahippocampal injections of paraquat (1 mumol) were prevented by administering it together with atropine (50 nmol; n=6 rats) or by giving it 60 min. after MK 801 (0.3 mg.kg-1 intraperitoneally). Systemic injections of paraquat (20-100 mg.kg-1) also produced forelimb clonus and rearing in 10 out of 15 animals. Neuronal cell death was found 24 hr later in 9 of these rats and was restricted to the pyriform cortex, the brain region with the highest concentrations of paraquat. Atropine (150 mg.kg-1 intraperitoneally given 60 min. previously) completely prevented the motor seizures but cell death still occurred in 2 of the 6 animals tested. In conclusion, both systemic and intrahippocampal injections of paraquat produced behavioural excitation accompanied 24 hr later by brain damage and antagonist studies suggested involvement of muscarinic and NMDA receptors in the neurotoxic mechanism.