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NMDA受体拮抗剂MK801对破伤风毒素所致大鼠海马神经元损失的预防作用

Prevention by the NMDA receptor antagonist, MK801 of neuronal loss produced by tetanus toxin in the rat hippocampus.

作者信息

Bagetta G, Nisticò G, Bowery N G

机构信息

Department of Pharmacology, School of Pharmacy, University of London.

出版信息

Br J Pharmacol. 1990 Dec;101(4):776-80. doi: 10.1111/j.1476-5381.1990.tb14156.x.

DOI:10.1111/j.1476-5381.1990.tb14156.x
PMID:2150767
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1917860/
Abstract
  1. The behavioural and neuropathological effects of tetanus toxin, microinjected directly into the hippocampus, were studied in rats. 2. A single dose (1000 minimum lethal doses, MLDs) of tetanus toxin, injected unilaterally into the hippocampus produced a time-dependent neuronal loss in the CA1 pyramidal cell layer. In comparison with the contralateral, untreated side these effects became statistically significant (P less than 0.05) 7 days (22.0 +/- 1.1% reduction) and 10 days (29.2 +/- 1.7% reduction) after the injection. No significant changes were observed 7 days after treatment with 500 MLDs whereas a reduction of 37.5 +/- 3.1% in the CA1 area cell number was produced 4 days after the injection of 2000 MLDs. 3. Behavioral stimulatory effects were also induced by tetanus toxin (1000 MLDs) within 48 h of the injection and these culminated in generalized convulsions 5-7 days later. Convulsions were observed after a shorter period of latency in rats receiving 2000 MLDs tetanus toxin whereas 500 MLDs were ineffective. 4. No behavioural and neuropathological effects were observed in rats treated with neutralized tetanus toxin (1000 MLDs), bovine serum albumin or phosphate buffer. 5. Pretreatment with MK801 (0.3 mg kg-1, i.p., given 1 h before and after the injection with tetanus toxin and then once daily for 4 or 7 days) prevented the behavioural and neuropathological effects induced by tetanus toxin (1000-2000 MLDs). In addition, such treatment fully protected the animals from the lethal effects induced by 1000 MLDs tetanus toxin. In addition, such treatment fully protected the animals from the lethal effects induced by 1000MLDs tetanus toxin. By contrast, pretreatment with diazepam (3.Omgkg-1, i.p.) using the same schedule as for MK801 did not antagonize the effects of tetanus toxin (1000-2000 MLDs). 6. In conclusion, the present experiments have demonstrated that the intrahippocampal injection of tetanus toxin produces in rats a dose- and time-dependent behavioural stimulation and neuronal loss in the CAl pyramidal cell layer which can be prevented by the non-competitive NMDA antagonist, MK801.
摘要
  1. 研究了直接微量注射到大鼠海马体中的破伤风毒素的行为和神经病理学效应。2. 单侧注射到海马体中的单剂量(1000个最小致死剂量,MLDs)破伤风毒素在CA1锥体细胞层产生了时间依赖性的神经元损失。与对侧未处理的一侧相比,这些效应在注射后7天(减少22.0±1.1%)和10天(减少29.2±1.7%)时具有统计学意义(P小于0.05)。注射500 MLDs后7天未观察到显著变化,而注射2000 MLDs后4天CA1区细胞数量减少了37.5±3.1%。3. 破伤风毒素(1000 MLDs)在注射后48小时内也诱导了行为刺激效应,这些效应在5 - 7天后 culminated 为全身性惊厥。接受2000 MLDs破伤风毒素的大鼠惊厥潜伏期较短,而500 MLDs无效。4. 用中和的破伤风毒素(1000 MLDs)、牛血清白蛋白或磷酸盐缓冲液处理的大鼠未观察到行为和神经病理学效应。5. 用MK801(0.3 mg kg-1,腹腔注射,在注射破伤风毒素前后1小时给予,然后每天一次,共4或7天)预处理可预防破伤风毒素(1000 - 2000 MLDs)诱导的行为和神经病理学效应。此外,这种处理可使动物完全免受1000 MLDs破伤风毒素诱导的致死效应。此外,这种处理可使动物完全免受1000MLDs破伤风毒素诱导的致死效应。相比之下,按照与MK801相同的给药方案用安定(3.0mgkg-1,腹腔注射)预处理并不能拮抗破伤风毒素(1000 - 2000 MLDs)的效应。6. 总之,本实验表明,海马体内注射破伤风毒素在大鼠中产生剂量和时间依赖性的行为刺激以及CA1锥体细胞层的神经元损失,而非竞争性NMDA拮抗剂MK801可预防这种情况。
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00fb/1917860/5e505ca1e905/brjpharm00248-0015-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00fb/1917860/09c7e2605b8a/brjpharm00248-0014-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00fb/1917860/4b70e2634aef/brjpharm00248-0015-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00fb/1917860/5e505ca1e905/brjpharm00248-0015-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00fb/1917860/09c7e2605b8a/brjpharm00248-0014-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00fb/1917860/4b70e2634aef/brjpharm00248-0015-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00fb/1917860/5e505ca1e905/brjpharm00248-0015-b.jpg

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