Global transcriptional disturbances are believed to play a major role in the course of epilepsy. Due to the high complexity, the neurobiological mechanisms underlying different susceptibility to seizure and epilepsy are not well known. A transcription factor called REST/NRSF (repressor element 1-silencing transcription factor/neuron-restrictive silencer factor) is believed to contribute to processes associated with seizure development. Its downstream genes, those encoding BDNF (brain-derived neurotrophic factor) and TrkB (BDNF receptor; tropomyosin receptor kinase B), are also thought to play a role. To verify this hypothesis, we used a PTZ kindling model of epilepsy and divided animals into groups according to their different susceptibility to seizure. The concentrations of REST/NRSF, BDNF, and TrkB protein and mRNA were measured in hippocampal homogenates.

The level of REST/NRSF protein measured 24 hours after the last PTZ injection was increased in animals resistant to kindling and was unchanged in groups of rats kindled after 5, 10 and 20 in.ections of PTZ. In contrast, TrkB protein concentration was enhanced in all kindled rats and was unchanged in the resistant rats. There were no changes in the protein concentration of BDNF in rats with different susceptibility to kindling; however, data from the combined kindled groups vs. the resistant group revealed an increased level of BDNF in resistant animals.

In sum, the increased level of protein REST/NRSF in resistant animals may reflect its neuroprotective role against seizure development. The increased concentration of TrkB protein in kindled animals indicates its pivotal role in the process of epileptogenesis. We propose that in resistant rats, REST/NRSF could contribute to the prevention of TrkB activation related to seizures.

全球转录紊乱被认为在癫痫病程中起主要作用。由于高度复杂，对癫痫发作和癫痫不同易感性的神经生物学机制尚不清楚。一种称为 REST/NRSF（阻遏元件 1 沉默转录因子/神经元限制性沉默因子）的转录因子被认为有助于与癫痫发作相关的过程。其下游基因，即编码 BDNF（脑源性神经营养因子）和 TrkB（BDNF 受体；原肌球蛋白受体激酶 B）的基因，也被认为起作用。为了验证这一假设，我们使用了癫痫的 PTZ 点燃模型，并根据动物对癫痫发作的不同易感性将其分组。REST/NRSF、BDNF、

在最后一次 PTZ 注射后 24 小时测量的 REST/NRSF 蛋白水平在抗点燃的动物中增加，而在注射 5、10 和 20 次 PTZ 后点燃的大鼠组中没有变化。相比之下，TrkB 蛋白浓度在所有点燃的大鼠中都有所提高，而在抗性大鼠中没有变化。不同点燃敏感性大鼠BDNF蛋白浓度无变化；然而，来自联合点燃组与抗性组的数据显示抗性动物中 BDNF 的水平增加。

总之，抗性动物中蛋白质 REST/NRSF 水平的增加可能反映了其对癫痫发作的神经保护作用。点燃动物中 TrkB 蛋白浓度的增加表明其在癫痫发生过程中的关键作用。我们建议在抗性大鼠中，REST/NRSF 可能有助于预防与癫痫发作相关的 TrkB 激活。