Effects of clomethiazole on spreading depression in the rat hippocampal slice

Clomethiazole is neuroprotective in a variety of animal models of ischaemic stroke, but the mechanism is unclear. This study examined whether clomethiazole is able to modify spreading depression elicited in rat hippocampal slices. When spreading depression was induced by superfusion with high K+ medium (50 mM), clomethiazole at 100 mu M reduced its duration. Both the amplitude and duration of spreading depression were reduced at 200 mu M. Clomethiazole at 200 mu M tended to reduce the amplitude of the K+-induced shift in direct current (DC) potential but this was not statistically significant. When a pair- of K+ pulses were presented, 30 min apart, the second produced a smaller DC potential than the first. Clomethiazole at 200 mu M increased the size of the ratio of these responses. Superfusion with a hypoxic solution induced spreading depression observed as a shift in the DC field potential. The amplitude of this was decreased significantly by clomethiazole at 200 mu M. With intracellular recordings, the effects of clomethiazole were quantified by measuring the time from the peak K+-induced depolarisation to the recovery of membrane potential following the period of hyperpolarisation. Clomethiazole did not reduce this period significantly. It is concluded that clomethiazole can reduce some forms of spreading depression, but only at the higher concentrations tested. It is unlikely that this effect contributes to its neuroprotective properties. (C) 2000 Elsevier Science B.V. All rights reserved.