Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
PLoS One. 2013 Aug 28;8(8):e72716. doi: 10.1371/journal.pone.0072716. eCollection 2013.
In models of status epilepticus ghrelin displays neuroprotective effects mediated by the growth hormone secretagogue-receptor 1a (GHS-R1a). This activity may be explained by anticonvulsant properties that, however, are controversial. We further investigated neuroprotection and the effects on seizures by comparing ghrelin with a more effective GHS-R1a agonist, JMV-1843. Rats were treated either with ghrelin, JMV-1843 or saline 10 min before pilocarpine, which was used to induce status epilepticus. Status epilepticus, developed in all rats, was attenuated by diazepam. No differences were observed among the various groups in the characteristics of pilocarpine-induced seizures. In saline group the area of lesion, characterized by lack of glial fibrillary acidic protein immunoreactivity, was of 0.45 ± 0.07 mm(2) in the hippocampal stratum lacunosum-moleculare, and was accompanied by upregulation of laminin immunostaining, and by increased endothelin-1 expression. Both ghrelin (P<0.05) and JMV-1843 (P<0.01) were able to reduce the area of loss in glial fibrillary acidic protein immunostaining. In addition, JMV-1843 counteracted (P<0.05) the changes in laminin and endothelin-1 expression, both increased in ghrelin-treated rats. JMV-1843 was able to ameliorate neuronal survival in the hilus of dentate gyrus and medial entorhinal cortex layer III (P<0.05 vs saline and ghrelin groups). These results demonstrate diverse protective effects of growth hormone secretagogues in rats exposed to status epilepticus.
在癫痫持续状态模型中，ghrelin 通过生长激素促分泌素受体 1a (GHS-R1a) 发挥神经保护作用。这种活性可能是由抗惊厥特性引起的，但这些特性存在争议。我们通过比较 ghrelin 和更有效的 GHS-R1a 激动剂 JMV-1843，进一步研究了神经保护作用和对癫痫发作的影响。大鼠在给予毛果芸香碱之前 10 分钟分别用 ghrelin、JMV-1843 或生理盐水处理，以诱导癫痫持续状态。所有大鼠均发生癫痫持续状态，用地西泮减轻。在毛果芸香碱诱导的癫痫发作的特征方面，各组之间没有差异。在生理盐水组中，海马层状分子层中缺乏神经胶质纤维酸性蛋白免疫反应性的病变面积为 0.45 ± 0.07 mm(2)，并伴有层粘连蛋白免疫染色上调和内皮素-1 表达增加。ghrelin (P<0.05) 和 JMV-1843 (P<0.01) 均能减少神经胶质纤维酸性蛋白免疫染色的缺失面积。此外，JMV-1843 对抗 ghrelin 处理大鼠中增加的层粘连蛋白和内皮素-1 表达的变化 (P<0.05)。JMV-1843 能够改善齿状回门区和内侧前额叶皮质层 III 的神经元存活 (P<0.05 与生理盐水和 ghrelin 组相比)。这些结果表明，生长激素促分泌素在暴露于癫痫持续状态的大鼠中具有不同的保护作用。
