El mice : Seizure mechanisms and their management

本课题组的所有实验结果如下：1.在出生后早期，脑和肝脏的氨基酸代谢和基因活性，包括聚A^+RNA和钠通道mRNA的表达，都是异常的。观察EL小鼠惊厥后即刻脑组织c-fos基因的表达。观察神经元生长、发育和分化的障碍。在未加任何惊厥剂的情况下，可检测到初级弯曲神经元神经细胞膜的兴奋性状态。对海马神经元继发性全身性癫痫的发病机制进行了研究。在海马区观察到细胞数量和树突的减少，以及蝇草酚结合部位的减少。兴奋性神经递质结合部位出现致痫异常。在大脑中发现了GABA能、去甲肾上腺素能和谷氨酸受体的紊乱。GABA能和谷氨酸能神经元系统随着生长、发育或刺激而改变。在脑片和海马片观察到兴奋性和抑制性神经递质的异常释放。在大脑中发现了遗传上和异常高水平的犬尿氨酸、低水平的多巴胺和其他代谢紊乱。从骨骼到血液的钙转运减少是公认的。这种钙有效性的降低可能导致依赖钙调蛋白的胺合成减少，从而导致癫痫阈值降低。小鼠癫痫发作可被GABA_B受体激动剂巴氯芬和5-羟色胺再摄取抑制剂西酞普兰抑制。EL鼠的品系已经从遗传和微生物学上进行了控制，以保存和繁殖，并便于任何癫痫专家进行进一步的实验。

All experimental results by our research group are as follows :1. The amino acid metabolism and gene activity, including poly-A^+ RNA and sodium channel mRNA expression, were unusual at the early postnatal stage in the brain and liver.2. The expression of c-fos RNA was observed just after convulsion in the brain of seizure experienced El mice.3. Disturbances of neuronal growth, development and differentiation were observed. Excitatory state of neuronal membrane was detected without any convulsant in the primary curtured neuron.4. Mechanisms for onset of secondary generalized seizures were studied in the hippocampal neurons.5. Decreased cell numbers and dendrites, and also muscimol binding sites were observed in the hippocampal region.6. Epileptogenic abnormalities in the excitatory neurotransmitter binding sites were recognized.7. Disorders in the GABAergic, noradrenergic, and glutamateric receptors were found in the brain.8. GABAergic and glutamatergic neuronal systems changed with growth, development or stimulations.9. Abnormal release of excitatory and inhibitory neurotransmitters was observed in the cerebral and hippocampal slices.10. Genetically and extraordinally higher level of kynurenine, lower level of dopamine, and other metabolic disorders, were found in the brain.11. Decreased transport of Ca into blood from the bone was recognized. This decreased availability of Ca may result in a decrease of calmodulin dependent synthesis of amines, which leads to a lowered seizure threshold.12. El mouse seizures were inhibited by baclofen, a GABA_B receptor agonist, and citalopram, an inhibitor for serotonin re-uptake.13. El mouse strain has been controlled genetically and microbiologically to keep and to breed and also to be easy available to any epileptologists for further experiments.