André V, Ferrandon A, Marescaux C, Nehlig A
INSERM U 398, Faculty of Medicine, Université Louis Pasteur, 11 Rue Humann, 67085, Strasbourg, France.
Epilepsy Res. 2000 Nov;42(1):7-22. doi: 10.1016/s0920-1211(00)00153-4.
Electroconvulsive therapy, which is used to treat refractory major depression in humans increases seizure threshold and decreases seizure duration. Moreover, the expression of brain derived neurotrophic factor induced by electroshocks (ECS) might protect hippocampal cells from death in patients suffering from depression. As temporal lobe epilepsy is linked to neuronal damage in the hippocampus, we tested the effect of repeated ECS on subsequent status epilepticus (SE) induced by lithium-pilocarpine and leading to cell death and temporal epilepsy in the rat. Eleven maximal ECS were applied via ear-clips to adult rats. The last one was applied 2 days before the induction of SE by lithium-pilocarpine. The rats were electroencephalographically recorded to study the SE characteristics. The rats treated with ECS before pilocarpine (ECS-pilo) developed partial limbic (score 2) and propagated seizures (score 5) with a longer latency than the rats that underwent SE alone (sham-pilo). Despite this delay in the initiation and propagation of the seizures, the same number of ECS- and sham-pilo rats developed SE with a similar characteristic pattern. The expression of c-Fos protein was down-regulated by repeated ECS in the amygdala and the cortex. In ECS-pilo rats, c-Fos expression was decreased in the piriform and entorhinal cortex and increased in the hilus of the dentate gyrus. Neuronal damage was identical in the forebrain areas of both groups, while it was worsened by ECS treatment in the substantia nigra pars reticulata, entorhinal and perirhinal cortices compared to sham-pilo rats. Finally, while 11 out of the 12 sham-pilo rats developed spontaneous recurrent seizures after a silent period of 40+/-27 days, only two out of the 10 ECS-pilo rats became epileptic, but after a prolonged latency of 106 and 151 days. One ECS-pilo rat developed electrographic infraclinical seizures and seven did not exhibit any seizures. Thus, the extensive neuronal damage occurring in the entorhinal and perirhinal cortices of the ECS-pilo rats seems to prevent the establishment of the hyperexcitable epileptic circuit.
电休克疗法用于治疗人类难治性重度抑郁症，可提高癫痫阈值并缩短癫痫持续时间。此外，电击（ECS）诱导的脑源性神经营养因子表达可能保护抑郁症患者的海马细胞免于死亡。由于颞叶癫痫与海马体中的神经元损伤有关，我们测试了重复ECS对锂-匹罗卡品诱导的后续癫痫持续状态（SE）的影响，该状态会导致大鼠细胞死亡和颞叶癫痫。通过耳夹对成年大鼠施加11次最大强度的ECS。最后一次施加是在锂-匹罗卡品诱导SE的前两天。对大鼠进行脑电图记录以研究SE特征。与单独接受SE的大鼠（假手术-匹罗卡品组）相比，匹罗卡品前接受ECS治疗的大鼠（ECS-匹罗卡品组）出现部分边缘性发作（评分2）和扩展性发作（评分5），且潜伏期更长。尽管发作的起始和传播有所延迟，但相同数量的ECS-匹罗卡品组和假手术-匹罗卡品组大鼠出现了具有相似特征模式的SE。重复ECS使杏仁核和皮质中的c-Fos蛋白表达下调。在ECS-匹罗卡品组大鼠中，梨状皮质和内嗅皮质中的c-Fos表达降低，齿状回门区中的c-Fos表达增加。两组大鼠前脑区域的神经元损伤相同，但与假手术-匹罗卡品组大鼠相比，ECS治疗使黑质网状部、内嗅皮质和嗅周皮质的神经元损伤加重。最后，12只假手术-匹罗卡品组大鼠中有11只在40±27天的无发作期后出现自发性复发性癫痫，而10只ECS-匹罗卡品组大鼠中只有2只癫痫发作，但潜伏期延长至106天和151天。1只ECS-匹罗卡品组大鼠出现脑电图下临床发作，7只未出现任何发作。因此，ECS-匹罗卡品组大鼠内嗅皮质和嗅周皮质中发生的广泛神经元损伤似乎阻止了过度兴奋的癫痫回路的建立。
