NEUROPROTECTIVE EFFECT OF KETAMINE ADMINISTERED AFTER STATUS EPILEPTICUS ONSET
NEUROPROTECTIVE EFFECT OF KETAMINE ADMINISTERED AFTER STATUS EPILEPTICUS ONSET
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DOI：
10.1111/j.1528-1157.1995.tb00979.x
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发表时间：
1995-02-01
期刊：
影响因子：
5.6
通讯作者：
FUJIKAWA, DG
中科院分区：
文献类型：
--
作者：
FUJIKAWA, DG
我们研究了在锂-匹罗卡品诱导的癫痫持续状态（SE）发作后给予非竞争性N-甲基-D-谷氨酸（NMDA）拮抗剂氯胺酮的神经保护作用。在Wistar大鼠中用氯化锂（3 mEq/kg）和毛果芸香碱（PC）（30-60 mg/kg，腹膜内，i. p.）诱导癫痫发作。SE发作后15分钟，腹膜内注射氯胺酮100 mg/kg或生理盐水，SE发作后3 h分别腹腔注射阿托品、地西泮（DZP）和苯巴比妥（PB）终止癫痫发作。24小时后，对大鼠进行脑灌注固定，随后进行脑处理以进行光学显微镜检查。给予生理盐水的大鼠（n = 5）在检查的25个脑区中的24个中有神经元损伤。给予氯胺酮的大鼠（n = 7）在24个受损区域中的22个中具有显著的神经保护作用。氯胺酮减少癫痫发作放电的幅度，并在3只大鼠EEG癫痫发作活动在30分钟内停止，这些大鼠都没有神经元损伤。在其他4只大鼠中，EEG发作放电持续>90 min;在这些动物中，24个受损区域中的21个受到保护。相比之下，1小时高剂量PC诱导SE（400 mg/kg i. p.，无氯化锂预给药）的大鼠有14个受损区域，其中7个与持续电图癫痫发作的氯胺酮亚组的未受损区域显著不同。因此，氯胺酮在SE发作后给药时具有显著的神经保护作用，无论癫痫发作放电是否消除。
We investigated the neuroprotective effect of the noncompetitive N-methyl-D-asparatate (NMDA) antagonist ketamine when administered after onset of lithium-pilocarpine-induced status epilepticus (SE). Seizures were induced in Wistar rats with lithium chloride (3 mEq/kg) and pilocarpine (PC) (30-60 mg/kg intraperitoneally, i.p.). Fifteen minutes after SE onset, either ketamine 100 mg/kg or normal saline was injected i.p., and 3 h after SE onset atropine, diazepam (DZP), and phenobarbital (PB) were administered i.p. to terminate the seizures. Twenty-four hours later, rats underwent brain perfusion-fixation, with subsequent brain processing for light-microscopic examination. Rats administered saline (n = 5) had neuronal damage in 24 of 25 brain regions examined. Rats administered ketamine (n = 7) had significant neuroprotection in 22 of 24 damaged regions. Ketamine reduced the amplitude of seizure discharges, and in 3 rats EEG seizure activity ceased in 30 min; none of these rats had neuronal damage. In the other 4 rats, EEG seizure discharges persisted >90 min; in these animals, 21 of 24 damaged regions were protected. In contrast, rats with 1-h high-dose PC-induced SE (400 mg/kg i.p. without lithium chloride preadministration) had 14 damaged regions, of which 7 were significantly different from the undamaged regions of the ketamine subgroup with persistent electrographic seizures. Thus, ketamine is remarkably neuroprotective when administered after onset of SE, whether or not seizure discharges are eliminated.