Production under control of microorganism and pharmacological use of spontaneously epileptic rats.

微生物控制下的生产和自发性癫痫大鼠的药理用途。

基本信息

批准号：
06557141
负责人：
SASA Masashi
金额：
$ 4.99万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

The spontaneously epileptic rat (SER : zi/zi, tm/tm) is obtained by mating heterozygous tremor rat (tm/+) with monozygous zitter rat (zi/zi). SER shows both tonic convulsion and absence-like seizures spontaneously. The seizures are easily induced by light stimuli such as tactile stimulation. SER is now reproduced by mating the zitter-homozygous and tremor-heterozygous animals (zi/zi, tm/+) each other. When male and female animals were housed in clean racks with a ratio of 1 : 1 or 1 : 2 at 22-26ﾟC and 50-65 % relative humidity in stress-free conditions, the SER was most efficiently reproduced. Previous attempts with a single i.v.injection of thyrotropine releasing hormone analogue, CNK-602A.inhibited both tonic and absence-like seizures. Under such conditions, effects of chronic intake of CNK-602A on epileptic seizures and survival time of SER were examined. CNK-602A significantly inhibited tonic convulsion and extended survival time from 19.0 <plus-minus> 0.6 to 21.7 <plus-minus>0.7 w … More eeks without affecting weight gain and serum T3 and T4 levels. These findings suggestthat this drug may be effective against convulsive seizures in patients with epilepsy. In slice preparations of SER hippocampus, long-lasting depolarization shifts accompanied repetitive firings in the CA1 cells were evoked with a single electronic stimulation of mossy fiber. This phenomenon were blocked by calcium channel blockers such as nicardipine. In addition, the calcium voltage induced by intracellular depolarizing pulse was inhibited by nicardipine at a dose lower than that required to inhibit the voltage of normal rats. In isolated CA3 neurons studied with patch clamp method revealed that the I-V curve of calcium currents in young SER before induction of epileptic seizures resembled that of normal Kyoto Wistar rat. However, the threshold for openning the calcium channel was lower in matured SER than that observed in normal rat. In addition, this current was inhibited by calcium antagonists at a dose much lower than that required to block the current in normal rats. Furthermore, a newly synthesized calcium channel blocker, S-312-d, inhibited the epileptic seizures in SER subjected to both single and repeated (once daily for 4 consecutive days) oral administrations. These findings suggest that calcium channel blockers are useful in human epilepsy. In summary, SER may be serve as a useful animal model for acute and chronic evaluations of novel antiepileptic drugs against non-remeidal epilepsy. Moreover, SER may also be used to study the mechanism underlying epileptic seizu Less

赞助的癫痫大鼠（SER：ZI/ZI，TM/TM）是通过与单氮基Zitter大鼠（ZI/ZI）配合杂合树（TM/+）获得的。 SER既表现出滋补性抽搐，又显示出类似癫痫发作的赞助。癫痫发作很容易被光刺激（例如触觉刺激）诱导。现在，通过将zitter-homozygous和震颤 - 杂合动物（Zi/Zi，tm/+）交配来复制Ser。当将男性和雌性动物放在干净的架子中，在22-26°C时为1：1或1：2，在无压力条件下相对湿度为50-65％时，SER最有效地再现了。以前的腹膜注射促甲状腺粒细胞的尝试释放了辣椒类似物，CNK-602A。抑制了滋补和缺失的癫痫发作。在这种情况下，检查了CNK-602A慢性摄入对癫痫发作和SER存活时间的影响。 CNK-602A显着抑制了补品抽搐，并从19.0 <plus-minus> 0.6到21.7 <plus-minus> 0.7 W…更多的EEKS而不会影响体重增加和血清T3和T4水平。这些发现表明，该药物可能有效地防止癫痫患者的抽搐性癫痫发作。在海马Ser海马的切片制剂中，用单个电子刺激苔藓纤维唤起了CA1细胞中重复发射的长期去极化移位。这种现象被钙通道阻滞剂（如尼卡迪平）阻塞。另外，尼卡迪平的抑制细胞内去极化脉冲诱导的钙电压的剂量低于抑制正常大鼠电压所需的剂量。在用斑块夹的分离的CA3神经元中，研究表明，在诱导癫痫发作之前，年轻SER中钙电流的I-V曲线类似于正常的京都Wistar大鼠。但是，在成熟的Ser中，打开钙通道的阈值低于正常大鼠中观察到的阈值。此外，钙拮抗剂的抑制剂量低于阻断正常大鼠中电流所需的剂量。此外，新合成的钙通道阻滞剂S-312-D抑制了遭受单个和重复（连续4天每天一次）的SER中的癫痫发作。这些发现表明，钙通道阻滞剂在人癫痫中很有用。总而言之，SER可以用作对非恢复癫痫的新型抗癫痫药进行急性和慢性评估的有用动物模型。此外，SER还可以用于研究癫痫性seizu的基本机制