Actions of brain-protecting substances against both oxygen and glucose deprivation in the guinea pig hippocampal neurons studied in vitro.

A study was made of the protective effects of several drugs (mannitol, phenytoin, vitamin E and dexamethasone) on the electrical activities of guinea pig hippocampal neurons in vitro when they were treated with a bathing medium deprived of both oxygen and glucose. Using guinea pig hippocampal slices, antidromic field potentials in the granular cell layer of the dentate gyrus were recorded stimulating mossy fibers. A model of ischemia in vivo in the slices was achieved by removing both oxygen and glucose from the perfusing medium. In standard medium, after 10 min of both oxygen and glucose deprivation, the field potentials exhibited minimum recovery with an amplitude of 6% of the control after 60 min. The protective effect of the drugs was evaluated by recovery of the field potential amplitude of the 60 min post-deprivation response and histological examination of the brain slice tissue. Drugs were added during 30 min of pre-deprivation and during deprivation. In this experiment we demonstrated that (1) phenytoin and vitamin E clearly showed protective action against neuronal damage caused by both oxygen and glucose deprivation in guinea pig hippocampal slices, (2) combined application of these drugs was more effective, and (3) mannitol showed no protective action in vitro. It was also demonstrated that (4) the dentate antidromic field response can be a useful index of cell death.