Excitotoxicity plays an important role in the pathogenesis of diseases which are apparently different in their nature (stroke and neurodegenerative disorders). In brain ischemia the territory deprived totally from blood supply (core) is surrounded by the penumbra in the subsequent hours of the onset of ischemia. Here ce rebral blood flow is reduced to a level, where the electrophysiological function of the neurons ceased, and transient, but repetitive membran ion homeostasis disturbances occur. Some hours later, in lack of reperfusion, these cells also die as a result of necrosis or apop tosis. This 3-6 hour interval is called the 'therapeutic window'. In the core of the lesion cells quickly die, while in the penumbra acidosis and energy deficiency develop and the cells are still viable for some hours. Because of the reduced ATP synthesis, membrane pump functions deteorate, the cells become depolarized and a great amount of glutamate is released from them (strong excitotoxicity). This leads through mechanisms partly to acute neuronal swelling, partly to intracellular Ca++ accumulation. The latter triggers a destructive cascade resulting in delayed neuronal death'. Chronic ('weak') neurodegeneration can be suspected in the pathogenesis of different neurodegenerative disorders (e.g. Parkinson's disease, amyotrophic lateralsclerosis). In this case, any kinds of metabolic deficit leading to defective ATP production and glutamates toxicity result in neuronal cell death. Chronic neurodegeneration may develop even by normal glutamate transmission if the energy metabolism of the cell is disturbed for the reduced energy level will not be sufficient to repolarize the cell. The metabolic disturbance is caused mostly by the damage of any mitochondrial enzyme or enzyme complexes taking part in the terminal oxidation or oxidative phosphorilation of the cell.
|Number of pages||9|
|Journal||Lege Artis Medicinae|
|Publication status||Published - Sep 9 1998|
ASJC Scopus subject areas