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 clomethi azole is able to modify spreading depression elicited in rat hippocampal sl ices. When spreading depression was induced by superfusion with high K+ med ium (50 mM), clomethiazole at 100 mu M reduced its duration. Both the ampli tude and duration of spreading depression were reduced at 200 mu M. Clometh iazole at 200 mu M tended to reduce the amplitude of the K+-induced shift i n direct current (DC) potential but this was not statistically significant. When a pair- of K+ pulses were presented, 30 min apart, the second produce d a smaller DC potential than the first. Clomethiazole at 200 mu M increase d the size of the ratio of these responses. Superfusion with a hypoxic solu tion induced spreading depression observed as a shift in the DC field poten tial. 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 t o the recovery of membrane potential following the period of hyperpolarisat ion. Clomethiazole did not reduce this period significantly. It is conclude d that clomethiazole can reduce some forms of spreading depression, but onl y at the higher concentrations tested. It is unlikely that this effect cont ributes to its neuroprotective properties. (C) 2000 Elsevier Science B.V. A ll rights reserved.