Department of Medical Pathomorphology, Medical University of Białystok, 13 Waszyngtona St., 15-269 Białystok, Poland.
Folia Neuropathol. 2011;49(3):230-6.
The objective of the current ultrastructural study was to explore the potentiality of the neuroprotective effect of TPM against damage of pyramidal neurons in the hippocampal CA1 and CA3 sectors in an experimental model of febrile seizures (FS) in rats. The FS group exhibited variously pronounced submicroscopic lesions of the neuronal perikarya, including total cell disintegration. Advanced changes induced by hyperthermic stress were manifested by marked degenerative abnormalities, such as substantial swelling of the mitochondria, dilation, degranulation and disintegration of the granular endoplasmic reticulum, and vacuolar changes in the Golgi complex. The most substantially damaged pyramidal neurons showed features of aponecrosis (so-called "dark neurons"), resulting in a marked neuronal loss in the explored areas of the hippocampal cortex. The neurodegenerative changes were accompanied by distinct damage to the blood-brain barrier components. The administration of topiramate at a dose of 80/kg b.m. prior to the induction of hyperthermic stress (as prevention against febrile seizures) caused a substantial neuroprotective action - the drug efficiently lightened the neuronal damage, basically reduced cell aponecrosis and enhanced cell viability. However, TPM applied directly after FS induction did not exert any distinct neuroprotective effect on the perikarya of pyramidal neurons in the hippocampal cortex.
本超微结构研究的目的是探讨托吡酯（TPM）对发热性惊厥（FS）大鼠海马 CA1 和 CA3 区锥体神经元损伤的神经保护作用。FS 组表现出不同程度的神经元胞体亚微结构损伤，包括全细胞崩解。由高热应激引起的晚期变化表现为明显的退行性异常，如线粒体显著肿胀、颗粒内质网扩张、脱粒和崩解以及高尔基复合体空泡化。受损最严重的锥体神经元表现出凋亡特征（所谓的“暗神经元”），导致海马皮质研究区域的神经元明显丢失。神经退行性变化伴随着血脑屏障成分的明显损伤。在高热应激诱导前给予托吡酯 80/kg b.m. 的剂量（作为预防热性惊厥）可产生显著的神经保护作用 - 该药物有效地减轻神经元损伤，基本上减少细胞凋亡并提高细胞活力。然而，FS 诱导后直接应用 TPM 对海马皮质锥体神经元的胞体没有明显的神经保护作用。
