BRAIN DEVELOPMENT IN EXPERIMENTAL EPILEPSY: STATUS

这个项目将研究能量衰竭在大脑中的作用。 癫痫持续状态对新生儿和成人的损害。 我们的初步结果推翻了普遍接受的观点，即 癫痫持续状态不会导致严重的能量衰竭 无全身并发症，如缺氧症。此外, 来自其他实验室的最新结果表明，经典的 荷包牡丹碱癫痫持续状态模型不适合研究 细胞死亡的机制。这个项目将使用可靠的 常规产生神经元的癫痫持续状态模型 易受伤害的脑区出现坏死。这些型号将使用 新生猴的惊厥药荷包牡丹碱； 成年大鼠的氟乙基；电刺激穿孔剂 在老鼠身上的路径。初步结果表明，在这些模型中 神经元坏死将是足够可预测和广泛的。 因此，对细胞机制的平行生化研究 伤害是可以进行的。在那些生化研究中，三磷酸腺苷， 将测定磷酸肌酸、葡萄糖、糖原和乳酸。 在取自大脑关键区域的显微穿孔活组织检查中 状态下的液氮或微波辐射 癫痫。我们预测，能源短缺将永远是 在选择性神经元坏死的区域观察到，以及 在代谢旺盛的区域会出现乳酸积聚 脑梗塞。

This project will examine the role of energy failure in brain damage from status epilepticus both in neonates and in adults. Our preliminary results disprove the generally accepted idea that status epilepticus does not produce profound energy failure in the absence of systemic complications such as anoxemia. In addition, recent results from other laboratories suggest that the classical bicuculline model of status epilepticus is not adequate to study the mechanisms of cell death. This project will use reliable models of status epilepticus which routinely produce neuronal necrosis in vulnerable brain regions. These models will use the convulsants bicuculline in the newborn marmoset monkey; flurothyl in adult rats; and electrical stimulation of the perforant path in rats. Preliminary results suggest that in these models neuronal necrosis will be sufficiently predictable and widespread so that parallel biochemical studies on the mechanism of cell injury can be conducted. In those biochemical studies, ATP, phosphocreatine, glucose, glycogen and lactate will be measured in micropunch biopsies taken from key regions of brains fixed with either liquid nitrogen or microwave irradiation during status epilepticus. We predict that energy failure will invariably be observed in areas where selective neuronal necrosis develops, and that lactate accumulation will be seen in areas in hypermetabolic infarction.