氯胺酮在利多卡因化学性点燃大鼠的量效关系

目的观察氯胺酮对大鼠化学性点燃模型的作用,并了解其是否有量效关系。方法建立利多卡因化学性点燃模型大鼠,观察氯胺酮对利多卡因点燃的影响。结果氯胺酮20.0~30.0 mg.kg-1,ip可降低利多卡因化学点燃模型大鼠降低Rac ine's发作级别(P<0.05),并降低V级发作率。结论氯胺酮能抑制大鼠利多卡因化学性点燃发作,并有显著的量效关系。     

柴胡总皂甙对戊四氮慢性点燃大鼠痫性发作及脑电图的影响

目的 评价柴胡有效成分中柴胡总皂甙对戊四氮（PTZ）慢性点燃大鼠痫性发作及脑电图的影响。方法 将48只健康SD大鼠随机等分为6组,即空白组、生理盐水组、丙戊酸钠（VPA）组和柴胡总皂甙高、中、低3种剂量组,除空白组不做处理外．其他组采用腹腔注射PTZ进行慢性点燃造模,造模同时给予以上不同处理因素,连续4周．在此期间记录大鼠痫性发作级别及次数,最后描记大鼠脑电图。结果 柴胡总皂甙高、中、低3个剂量组在实验2周时可以降低大鼠的痫性发作率,其中以高剂量组显著（P〈0．05）,柴胡皂甙高剂量组应用4周时能明显降低PTZ慢性点燃大鼠的点燃率（P〈0．05）,并明显降低痫性发作级别（P〈0．01）;各组间脑电图也存在一定差异。结论 柴胡总皂甙可拮抗PTZ慢性点燃大鼠的痫性发作．并有一定的对抗PTZ慢性点燃作用。     

戊四氮点燃大鼠慢性癫癎模型的建立及评价

目的建立戊四氮点燃的大鼠慢性癫痫模型。方法对大鼠隔日腹腔注射惊厥阈下低、中、高3个剂量（20、40、60mg／kg）的戊四氮，通过观察动物体重变化、行为表现及电生理等资料评价3个剂量的戊四氮，在模型点燃过程中产生的不同效应。结果惊厥阈下低剂量（20mg／kg）不能有效点燃模型。动物行为表现为烦躁；中剂量组大鼠（40mg／kg）给药后惊厥发作平稳，发作级别由轻到重循序渐进。发作缓解后动物活动自如；高剂量组大鼠（60mg／kg）给药后发生持续惊厥大发作，死亡率高。结论戊四氮惊厥阈下中剂量（40mg／kg）隔日给药。能有效点燃大鼠慢性癫痫。模型稳定、持久，点燃率较高、死亡率较低，为理想的致痴诱导剂量。     

海人酸杏仁核点燃大鼠癫痫模型的建立和评价

目的：建立和评价海人酸杏仁核微量注射点燃癫痫动物模型。方法：选用雄性Wistar大鼠,以杏仁核外侧基底核为给药靶点,在立体定位仪下,微量注射海人酸1 μg后进行大鼠的行为学和电生理学观察,并分别于第6、12、72 h和7、14、21 d对大鼠脑组织进行病理学观察。结果：海人酸微量注射后实验大鼠出现典型的癫痫发作过程,顶叶皮层脑电图依次出现多种形式的痫性放电,HE染色显示海马和颞叶皮层神经细胞的相应病理变化,点燃成功率为90%。结论：采用杏仁核海人酸微量注射方法成功建立了Wistar大鼠点燃癫痫模型,该模型适用于颞叶癫痫的相关研究。     

甘珀酸对点燃大鼠的保护作用和对连接蛋白32的影响

 目的观察甘珀酸(生胃酮)对戊四氮点燃大鼠的保护作用和对连接蛋白32的影响。方法观察戊四氮及生胃酮腹腔注射大鼠痫性发作等级及潜伏期的变化,并采用蛋白印迹法测定海马CX32的表达。结果20 mg·kg^-1生胃酮组大鼠痫性发作等级较致痫组低,潜伏期明显延长(P<0.05);10 mg·kg^-1生胃酮组大鼠痫性发作等级与致痫组无差异,但潜伏期较致痫组显著延长(P<0.01)。致痫组海马CX32表达较对照组明显增加,20 mg·kg^-1生胃酮组与对照组无显著差异。结论反复癫痫发作会诱导CX32异常表达,CX32和缝隙连接参与了癫痫的形成和点燃过程,缝隙连接阻滞剂生胃酮有较明确的抗癫痫作用。     

佐匹克隆对大鼠化学点燃效应的影响

①目的　探讨佐匹克隆 (zpl)对大鼠戊四唑 (PTZ)化学点燃和对小鼠氨基脲惊厥的影响。 ②方法制备大鼠PTZ化学点燃模型 ,对已点燃大鼠分别给予zpl 1 .5、3.0、5 .0mg/kg灌胃 ,30min后PTZ 35mg/kg腹腔注射 ,观察大鼠行为发作情况 ,大鼠行为发作按Ono标准分级 ,计算 6级发作百分率并与用药前比较 ;小鼠zpl(0 .5、1 .5、3.0mg/kg)灌胃给药 30min后 ,氨基脲 (1 5 0mg/kg)尾静脉注射 ,观察小鼠行为活动变化 ,记录小鼠阵挛惊厥的潜伏期及存活时间。③结果　zpl 3.0、5 .0mg/kg可降低点燃大鼠行为发作强度 ,与用药前比较其Ono分级和 6级发作的百分率均有显著性差异 (t =2 .1 9,P <0 .0 5 ,t =5 .2 6 ,P <0 .0 1 ;χ2 =4 .6 8,P <0 .0 5 ,χ2 =1 0 .74 ,P <0 .0 1 ) ;zpl 1 .5、3.0mg/kg灌胃用药延长了小鼠氨基脲惊厥的潜伏期及存活时间 ,与对照组比较有显著性差异 (t =2 .2 0～ 3.81 ,P <0 .0 5、0 .0 1 )。④结论　zpl对大鼠PTZ化学点燃和小鼠氨基脲惊厥均有明显的抑制作用     

杏仁基底外侧核电点燃癫痫模型的制作及观察

为了探讨杏仁基底外侧核电点燃癫痫模型的制作及意义,我们把双极电极插入大鼠左侧杏仁基底外侧核,给予慢性电刺激使大鼠达到点燃状态,观察其发作过程、行为改变并记录脑电图。结果发现29只接受刺激的大鼠,达到点燃的有24只,8.29±5.31次刺激出现5级瘸样发作,10.87±3.44次刺激达到点燃,没有因抽搐发作而致死的点燃大鼠。脑电图记录到后发放时程在32.05~51.65 s之间。行为观察发现点燃大鼠比对照组易激惹。说明杏仁基底外侧核电点燃大鼠癫痫模型便于从行为、脑电图等多方面进行观察,是研究人类癫痫机制、药物治疗和预防的良好工具。     

Effects of pentylenetetrazol kindling on glutamate receptor genes expression in the rat hippocampus

It has been hypothesized that changes in the excitatory amino acid receptor biosynthesis may be involved in the mechanism of kindling—an animal model of epileptogenesis. In order to test this hypothesis, we investigated the effects of pentylenetetrazol kindling on the expression of genes coding for NMDAR1 and GluR2 in the rat hippocampal formation. Pentylenetetrazol kindling decreased the hippocampal NMDAR1 mRNA level after 3 and 24 h; lowered the GluR2 flip level and elevated the flop mRNA one in the CA1 field and dentate gyrus after 3 and 24 h, respectively. A receptor autoradiography showed an increase in the [³H]MK-801 binding density in the hippocampus following both acute and repeated pentylenetetrazol administration. We conclude that an early occurrence of downregulation of the glutamate receptor gene expression may be an adaptive response of glutamate receptors to an oversupply of excitatory amino acids during repeated seizures.     

Some observations on the kindling process

1. Kindling is an animal model of epilepsy in which repeated administration of a subconvulsant stimulus, electrical or chemical, produces a gradually increasing electroencephalographic and behavioral response which culminates in a behavioral seizure.

2. The biological basis of the kindling effect remains unknown but alterations in neurotransmission figure prominently in most hypotheses. Several factors of kindling are considered as central to the phenomenon. It is most important to recognize that the development of kindling and a kindled seizure are not necessarily the same phenomenon.

3. Kindling is essentially a permanent change in the sensitivity of the brain to a stimulus. It therefore follows that the biological basis for kindling must be a permanent change. Permanent changes in neurotransmitter levels or receptor parameters have not been conclusively demonstrated in kindling. Other possible permanent changes include changes in Ca activated mechanisms which alter neuronal structures such as dendritic spines.

4. An essential component to the riddle of kindling is the absolute requirement for an inter-stimulus interval of at least 1–2 hours. This suggests that the biological process which leads to kindling occurs in this critical period. Recent experiments with cysteamine suggest that the events in this critical period can be manipulated chemically. An understanding of these events will help to clarify the biological basis of kindling.