Neuronal cell damage in the brain: possible involvement of oxidative mechanisms

Neuronal lesions in the brain occur in conditions associated with a reduced supply of oxygen (hypoxia and ischemia) and glucose (hypoglycemia) as well as in those associated with a pathologically enhanced neuronal activity (status epilepticus). In only two of these conditions (hypoxia and ischemia) are the lesions correlated to cellular oxygen lack, and gross energy failure is absent in one condition (status epilepticus). Although anaerobic mechanisms seem responsible for the cell injury in hypoxia and ischemia, oxidative mechanisms could operate in hypoglycemia and status epilepticus. Since the supply of oxygen has not ceased altogether in hypoxia and incomplete ischemia, and since reoxygenation/recirculation leads to a transient increase in tissue oxygen tensions, one cannot exclude the possibility that oxidative mechanisms contribute to the final damage following all types of cellular oxygen lack. We have failed to obtain evidence that peroxidative degradation of cellular constituents occurs in hypoglycemia and status epilepticus. Thus, there is neither a perturbation of the redox state of the glutathione pool of the tissue nor a measurable degradation of polyenoic phospholipid-bound fatty acids. It is emphasized that the cascade of events triggered by an accumulation of free polyenoic fatty acids, mainly arachidonic acid, may contribute to cell lesions by leading to cell edema and/or microcirculatory changes. During seizures, such an accumulation occurs even though energy failure is moderate and it may conceivably contribute to cell damage. In general, though, mechanisms of cell damage in the brain remain partly elusive.