The mode of death of epilepsy-induced "dark" neurons is neither necrosis nor apoptosis: an electron-microscopic study.
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.
Gallyas
Ferenc
F
Department of Neurosurgery, Faculty of Medicine, University of Pécs, H-7623 Pécs, Rét utca 2, Hungary. ferenc.gallyas.sen@aok.pte.hu
Kiglics
Viola
V
Baracskay
Péter
P
Juhász
Gábor
G
Czurkó
András
A
D015761:4-Aminopyridine; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure; D016923:Cell Death; D002470:Cell Survival / Q000502:physiology; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D009336:Necrosis / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000473:pathology* / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012270:Ribosomes / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D013997:Time Factors
D015761:4-Aminopyridine