Introduction:

Adult hippocampal neurogenesis is severely influenced in several models for Temporal Lobe Epilepsy (TLE). Proliferation and synaptic integration of neural precursors is increased in response to seizures. Part of the precursors migrates to ectopic locations, where they form aberrant connections. However no clear relationship between this altered neurogenesis and epileptogenesis has been demonstrated. In the present study we used low-dose, whole brain radiation to block hippocampal neurogenesis in a kindling model for TLE in order to further elaborate on a possible role of this altered neurogenesis in epileptogenesis.

Methods: 

Rats were implanted with a recording and stimulation electrode in the right hippocampus one week before half of the animals were exposed to low-dose (8Gy), whole brain radiation. One day after radiation rats were kindled by giving 48 stimulations on four alternating days. On the first and third day after radiation, rats were injected with BrDU (50 mg/kg, BID). One and two weeks after kindling acquisition rats were retested for their kindling response. Afterdisharge threshold (ADT) was determined on the beginning of each stimulation day. Afterdischarge duration (ADD) and clinical seizure severity (Racine stages 1-5) were compared between groups. Twenty-one days after radiation, BrDU and doublecortin (DCX) positive cells in dentate gyrus were counted.

Results: 

Radiation suppressed the level of neurogenesis almost completely during the first the first week after radiation, which coincides the kindling acquisition phase. Three weeks after radiation and after 70 kindling stimulations, neurogenesis was still reduced by 50%. Radiation also influenced kindling parameters such as ADT and clinical seizure severity. Radiation prevented an increase in ADT which became significantly lower in radiated rats from kindling day 3 on and stayed lower for the rest of the experiment. On the third and the fourth kindling day radiated rats developed more rapidly more severe seizures, which resulted in a significantly higher mean severity score on these days. This difference was no longer evident during the retest stimulations. No differences in ADD could be demonstrated during kindling.

Discussion: 

Our results show that less neurogenesis during kindling is associated with less inhibition in the hippocampus and a higher tendency of rats to display generalized tonic-clonic seizures. Whether the inhibition of neurogenesis is responsible for this enhanced excitability could not be concluded from this study. However our results argue against a major role of aberrant neurogenesis in the establishment of kindling since suppression of neurogenesis has no anti-epileptogenic effects in our kindling model.