BRAIN DEVELOPMENT IN EXPERIMENTAL EPILEPSY

描述（研究者摘要）：本研究的长期目标 项目是为了了解癫痫发作和大脑之间的关系， 发展如进度报告所示，我们最近 发现了一个例外的一般规则，即未成熟的大脑是 选择性地抵抗细菌引起的损伤。下组织生产的目标 这个项目的下一个阶段将是探索的限制， 例外的意义。这将在四个一般 （A）癫痫发作引起的神经元损伤，（在 齿状回，CC）致痫性，（D）诱导发芽。 A.我们将通过定量组织学方法确定 持续的穿通通路刺激诱导不可逆的神经元损失 在15日龄大鼠，并将比较分布和时间过程 在成年人中观察到的类似刺激后的损伤。我们 预期类似的刺激持续时间将诱导不太严重的 他说，年轻时就有军团，这种抵抗不会是绝对的。 我们将通过免疫细胞化学和原位杂交来确定 Hila神经元的亚群持续受损，并期望 不同的年龄分布。我们会善待动物 与NMDA和非NMDA谷氨酸受体阻滞剂。a我们预计， 用这些药剂保护特定的亚群我们将测试 SE对兔未成熟脑的影响， 出生时非常不成熟，豚鼠出生时非常成熟， 和中间的绒猴。 B。我们将研究持续的穿支通路刺激对 齿状回的成对脉冲抑制我们将跟随时间 在恢复期内这种抑制作用的丧失过程和 发芽期。 C.我们将研究病变的致痫性。我们预计 自发性癫痫发作和加速点燃将在 在足够严重的穿支通路刺激后， 诱导神经元损失。0.我们将通过Timm染色研究发芽， 免疫细胞化学和原位杂交研究GAP 43，NAP 2， 和GFAP。我们还将研究神经营养因子和 他们的受体。这些研究将确定海马神经元 在一些儿童早期癫痫发作的损害 物种，并应帮助临床医生了解基本原则 对非惊厥性癫痫发作的有效治疗。

DESCRIPTION (Investigator's Abstract): The long term objectives of this project are to understand the relationship between seizures and brain development. As shown in the progress report, we have recently discovered an exception to the general rule that the immature brain is selectively resistant to seizure-induced damage. The goals for the upcoming period of this project will be to explore the limits and significance of that exception. This will be done in four general areas: (A) seizure induced neuronal injury, ( of inhibition in the dentate gyrus, CC) epileptogenicity, (D) induction of sprouting. A. We will establish by quantitative histological methods whether sustained perforant path stimulation induces irreversible neuronal loss in 15 day old rats, and will compare the distribution and time course of damage to that observed in the adult after similar stimulation. We expect that similar durations of stimulation will induce less severe legions at younger ages, and that this resistance will not be absolute. We will define by immunocytochemistry and in situ hybridization the subpopulations of hila neurons which sustain damage, and expect a different distribution as a function of age. We will treat the animals with blockers of NMDA and non NMDA glutamate receptors.a We expect to protect selective subpopulations with those agents. We will test the effect of SE on the immature brain in the rabbit, a species which is very immature at birth, the guinea pig, which is very mature at birth; and the marmoset which is intermediate. B. We will study the effect of sustained perforant path stimulation on paired pulse inhibition in the dentate gyrus. We will follow the time course of this loss of inhibition during the recovery period and the period of sprouting. C. We will study the epileptogenicity of lesions. We expect that spontaneous seizures and accelerated kindling will be observed in animals following perforant path stimulation of sufficient severity to induce neuronal loss. 0. We will study sprouting by Timm stain, and by immunocytochemistry and in situ hybridization studies of GAP 43, NAP2, and GFAP. We will also study the induction of neurotrophins and of their receptors. These studies will define the risk of hippocampal damage from epileptic seizures during early childhood in several species, and should help clinicians to understand the basic principles that underlay treatment of non convulsive seizures.