Fabene Paolo F, Andrioli Anna, Priel Margareth R, Cavalheiro Esper A, Bentivoglio Marina
Department of Morphological and Biomedical Sciences, University of Verona, Verona, Italy.
Hippocampus. 2004;14(7):895-907. doi: 10.1002/hipo.20003.
Previous studies demonstrated that the spiny rat Proechimys guyannensis exhibits resistance to experimental epilepsy. Neural activation was studied in the Proechimys hippocampus, using Fos induction, within 24 h after pilocarpine-induced seizures; neurodegenerative events were investigated in parallel, using FluoroJade B histochemistry. These parameters were selected since pilocarpine-induced limbic epilepsy is known to elicit immediate early gene expression and cell loss in the hippocampus of seizure-prone laboratory rodents. At variance with matched experiments in Wistar rats, pilocarpine injection resulted in Proechimys in seizure episodes that, as previously reported, did not develop into status epilepticus. At 3 h and 8 h after seizure onset, Fos immunoreactivity filled the dentate gyrus of both rat species, and was quite marked in pyramidal cells of the Proechimys Ammon's horn. At 24 h, Fos immunoreactivity dropped in the Wistar hippocampus and persisted in Proechimys. At 8 h and 24 h, FluoroJade-stained neurons were very few in the Proechimys hippocampus, whereas they were abundant in that of Wistar rats. Double immunohistochemistry for Fos and parvalbumin, the protein expressed by fast-spiking hippocampal interneurons, indicated that Fos was induced up to 24 h in the vast majority of parvalbumin-containing cells of the Proechimys hippocampus, and in a minority of these cells in the Wistar hippocampus. The findings demonstrate that early postepileptic neurodegeneration is very limited in the Proechimys hippocampus, in which sustained Fos induction persists for several hours. The findings also indicate that Fos induction and persistence may not correlate with seizure intensity and may not be associated with neuronal death. Finally, the data implicate differential mechanisms of interneuron activity in anti-convulsant and pro-convulsant phenomena.
先前的研究表明，刺豚鼠（Proechimys guyannensis）对实验性癫痫具有抗性。在毛果芸香碱诱发癫痫发作后的24小时内，利用Fos诱导法研究了刺豚鼠海马体中的神经激活情况；同时，采用氟玉红B组织化学法并行研究了神经退行性变事件。选择这些参数是因为已知毛果芸香碱诱发的边缘性癫痫会在易患癫痫的实验啮齿动物海马体中引发即刻早期基因表达和细胞丢失。与在Wistar大鼠中进行的匹配实验不同，注射毛果芸香碱会使刺豚鼠出现癫痫发作，如先前报道的那样，不会发展为癫痫持续状态。癫痫发作开始后3小时和8小时，Fos免疫反应性充斥着两种大鼠的齿状回，在刺豚鼠海马角的锥体细胞中尤为明显。24小时时，Wistar大鼠海马体中的Fos免疫反应性下降，而在刺豚鼠中持续存在。在8小时和24小时时，刺豚鼠海马体中氟玉红染色的神经元很少，而在Wistar大鼠海马体中则大量存在。对Fos和小白蛋白（快速放电的海马中间神经元表达的蛋白质）进行双重免疫组织化学分析表明，在刺豚鼠海马体中，绝大多数含小白蛋白的细胞中Fos诱导持续长达24小时，而在Wistar大鼠海马体中只有少数此类细胞出现这种情况。研究结果表明，癫痫发作后早期海马体中的神经退行性变非常有限，其中Fos诱导持续数小时。研究结果还表明，Fos诱导和持续可能与癫痫发作强度无关，也可能与神经元死亡无关。最后，数据表明中间神经元活动的不同机制参与了抗惊厥和促惊厥现象。
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