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

由杂合子震颤大鼠（tm/+）与单合子震颤大鼠（zi/zi）交配获得自发性癫痫大鼠（SER: zi/zi, tm/tm）。SER显示强直性惊厥和自发性失神样发作。轻刺激如触觉刺激容易诱发癫痫发作。现在，通过将震颤纯合子动物和震颤杂合子动物（zi/zi, tm/+）相互交配来繁殖SER。当雄性和雌性动物在22-26含量、50- 65%的相对湿度和无压力条件下，以1:1或1:2的比例饲养在干净的架子上时，SER的繁殖效率最高。先前的尝试是单次静脉注射促甲状腺素释放激素类似物cnk - 602a，抑制强直性和缺席样癫痫发作。在此条件下，观察慢性摄入CNK-602A对癫痫发作及SER生存时间的影响。CNK-602A显著抑制强直性惊厥，延长生存时间，从19.0 <正-负> 0.6延长至21.7 <正-负>0.7 w .延长生存时间，而不影响体重增加和血清T3和T4水平。这些发现表明，这种药物可能对癫痫患者的惊厥发作有效。在SER海马切片制备中，单次电子刺激苔藓纤维可诱发CA1细胞中伴随重复性放电的长时间去极化移位。这种现象可被钙通道阻滞剂如尼卡地平阻断。此外，尼卡地平对细胞内去极化脉冲引起的钙电压的抑制作用低于正常大鼠的抑制剂量。膜片钳法研究离体CA3神经元，发现诱发癫痫发作前幼龄SER钙电流的I-V曲线与正常京都Wistar大鼠相似。然而，成熟SER的钙通道打开阈值比正常大鼠低。此外，这种电流被钙拮抗剂所抑制，其剂量远低于正常大鼠阻断电流所需的剂量。此外，新合成的钙通道阻滞剂S-312-d可抑制单次和多次（每天一次，连续4天）口服SER的癫痫发作。这些发现表明钙通道阻滞剂对人类癫痫是有用的。综上所述，SER可作为一种有用的动物模型，用于评估新型抗癫痫药物对非补救性癫痫的急性和慢性疗效。此外，SER也可用于研究癫痫发作的机制

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