Abstracts

A common feature in kindling and status epilepticus models for Temporal Lobe Epilepsy (TLE) is enhanced neurogenesis in the subgranular layer of the hippocampus. Although there is evidence that some of these newborn neurons migrate towards ectopic locations and have abnormal firing behaviour, no clear relationship between enhanced neurogenesis and epileptogenesis has been demonstrated. In the present study we investigated the effect of blocking neurogenesis by low dose whole brain [gamma]-irradiation on hippocampal kindling epileptogenesis., Female rats (n=16) were implanted with a bipolar recording and stimulation electrode in the right dorsal hippocampus. One week after implantation half of the rats were subjected to low-dose (8 Gy) whole brain irradiation. One or two days after irradiation, rats were subjected to a rapid alternate day kindling acquisition protocol and received 48 stimulations spread over 4 alternating days. One and two weeks after termination of kindling acquisition, rats were retested by giving ten additional stimulations per test. The afterdischarge threshold, afterdischarge duration and the clinical seizure severity (Racine stages 1-5) were compared between irradiated and non-irradiated rats., All rats displayed afterdischarges and clinical seizures with an increasing length and severity, until they displayed five or more consecutive stage 5 seizures and were labelled fully kindled. At kindling day 3 and 4 mean seizure severity in irradiated rats was significantly worse compared to non-irradiated rats. This difference was evident because seizures in irradiated rats developed more quickly to the most severe seizure state compared to seizures in non-irradiated rats. In line with these differences, afterdischarge threshold at kindling day 4 was significantly lower in irradiated compared to non-irradiated rats. All these differences were temporary and could no longer be demonstrated during retest stimulations., Low-dose whole brain irradiation, administered in order to block neurogenesis, leads to a lowered threshold to electrically evoke an epileptic event one week after irradiation. At this time point, irradiated rats also displayed more rapidly more severe seizures compared to non-irradiated rats. These effects were only temporary and no longer evident two and three weeks after irradiation. We can conclude that blocking neurogenesis by low-dose whole brain irradiation has mild accelerating but temporary effects on epileptogenesis., (Supported by the Institute for the Promotion of Innovation through Science and Technology (IWT) in Flanders and UCB Pharma.)