Department of Neurosurgery, Faculty of Medicine, University of Pécs, H-7623 Pécs, Rét utca 2, Hungary.
Brain Res. 2008 Nov 6;1239:207-15. doi: 10.1016/j.brainres.2008.08.069. Epub 2008 Sep 4.
Morphological aspects of the formation and fate of neurons that underwent dramatic ultrastructural compaction ("dark" neurons) induced by 4-aminopyridine epilepsy were compared in an excitotoxic and a neighboring normal-looking area of the rat brain cortex. In the excitotoxic area, the later the ultrastructural compaction began after the outset of epilepsy, the higher the degree of mitochondrial swelling and ribosomal sequestration were; a low proportion of the affected neurons recovered in 1 day; the others were removed from the tissue through a necrotic-like sequence of ultrastructural changes (swelling of the cell, gradual disintegration of the intracellular organelles and dispersion of their remnants into the surroundings through large gaps in the plasma and nuclear membranes). In the normal-looking area, the ultrastructural elements in the freshly-formed "dark" neurons were apparently normal; most of them recovered in 1 day; the others were removed from the tissue through an apoptotic-like sequence of ultrastructural changes (the formation of membrane-bound, electrondense, compact cytoplasmic protrusions, and their braking up into membrane-bound, electrondense, compact fragments, which were swallowed by phagocytotic cells). Since these ultrastructural features differ fundamentally from those characteristic of necrosis, it seems logical that, in stark contrast with the prevailing conception, the cause of death of the epilepsy-induced "dark" neurons in the normal-looking cortical area cannot be necrosis. An apoptotic origin can also be precluded by virtue of the absence of its characteristics. As regards the excitotoxic environment, it is assumed that pathobiochemical processes in it superimpose a necrotic-like removal process on already dead "dark" neurons.
形态学方面的形成和命运的神经元经历了戏剧性的超微结构压实(“暗”神经元)诱导的 4 - 氨基吡啶癫痫在兴奋毒性和相邻的正常外观的大鼠大脑皮层区进行了比较。在兴奋毒性区，超微结构压实后发生癫痫的时间越晚，线粒体肿胀和核糖体隔离的程度越高;受影响的神经元在 1 天内恢复的比例较低;其余的通过类似于坏死的超微结构变化序列(细胞肿胀、细胞内细胞器逐渐解体，并通过质膜和核膜上的大间隙将其残留物分散到周围环境中)从组织中去除。在外观正常的区域，新形成的“暗”神经元中的超微结构元素明显正常;其中大多数在 1 天内恢复;其余的通过类似于凋亡的超微结构变化序列(形成膜结合的、电子致密的、紧凑的细胞质突起，以及它们断裂成膜结合的、电子致密的、紧凑的片段，被吞噬细胞吞噬)从组织中去除。由于这些超微结构特征与坏死的特征根本不同，因此，与普遍的概念形成鲜明对比的是，在外观正常的皮质区癫痫诱导的“暗”神经元的死亡原因不可能是坏死，这似乎是合乎逻辑的。由于缺乏其特征，凋亡起源也可以排除。至于兴奋毒性环境，假设其病理生物化学过程会在已经死亡的“暗”神经元上叠加类似于坏死的清除过程。
