Blockade of spreading depression in chronic epileptic rats: reversion by diazepam

Following pilocarpine-induced status epilepticus, rats become chronically epileptic showing 2-3 spontaneous recurrent seizures per week. The aim of this work was to verify the characteristics of spreading depression (SD) in these chronic epileptic rats (n = 16). SD was evoked in one point of the frontal cortex by topical application of KCl solution at 20 min intervals, and recordings were made in two points over the parietal cortex (a 'near' point and a 'remote' one, about 3 and 8 mm posterior to the stimulating region, respectively). In all control animals (n = 10), KCl stimulation elicited SD which in 100% of the cases propagated regularly to the two recording points. In the chronic epileptic rats only about 50% of the KCl applications were effective in eliciting SD, detected at the 'near' recording point. Of these, only 3% propagated to the 'remote' recording point. In eight of the above epileptic rats, diazepam (5-10 mg/kg, i.v.) was injected after 1-2 h of recording, when SD incidence in response to KCl stimulation has been established. After diazepam, the incidence of SDs propagating regularly to the 'near' and to the 'remote' recording points increased significantly, (132 and 53 SDs, respectively, out of 139 KCl stimulations), as compared with the incidence in the pretreatment period (33 and 1, respectively, out of 63 stimulations; P < 0.005). These data indicate an impairment in the susceptibility to cortical SD in chronic epileptic rats suggesting modifications in cortical excitability in the pilocarpine model of epilepsy. They also indicate a facilitatory effect of diazepam on SD, confirming previous observations in non-epileptic rats.