Increased afterdischarge threshold during kindling in epileptic rats

Abstract

The effects of daily electrical kindling stimulation of the perforant pathway were investigated in an excitotoxic rat model of epilepsy with chronic seizures in order to learn whether the preexisting epileptic condition would facilitate or retard kindling. Sprague-Dawley rats with recurrent spontaneous seizures 4–8 months after unilateral intrahippocampal kainic acid (KA) injection were implanted with recording electrodes in the hippocampus and stimulating electrodes in the perforant path. Daily stimulation for 10 s at 5 Hz was given for 15 days. The afterdischarge (AD) threshold and the AD duration of kindled KA rats were compared before and during kindling with those of a kindled control group. In the control group, as expected, mean AD thresholds decreased (P<0.01), while AD duration progressively increased. Although AD threshold was the same in KA and control groups at the start of kindling, in the KA group a significant increase in threshold occurred from the beginning to the end of kindling (P<0.01). Behaviorally, KA rats showed stage 4 or 5 seizures on the first stimulation, and stage 3–5 seizures during the remainder of kindling. Paired pulse testing showed facilitation of late components of the dentate gyrus field potential at the beginning of kindling, and suppression of late components at the end, in the KA rats. A significant decrease in the rate of spontaneous seizures in KA rats was noted during the period of kindling (P=0.04). These results suggest that electrical stimulation of the perforant path may strengthen homeostatic seizure suppressing mechanisms, and may provide insights into novel approaches to the treatment of clinical seizures in temporal lobe epilepsy.