Neuronal cell death in a rat model for mesial temporal lobe epilepsy is induced by the initial status epilepticus and not by later repeated spontaneous seizures.
OBJECTIVE
To determine whether repeated seizures contribute to hippocampal sclerosis, we investigated whether cell loss in the (para) hippocampal region was related to the severity of chronic seizure activity in a rat model for temporal lobe epilepsy (TLE).


METHODS
Chronic epilepsy developed after status epilepticus (SE) that was electrically induced 3-5 months before. The presence of neuronal damage was assessed by using Fluoro-Jade and dUTP nick end-labeling (TUNEL) of brain sections counterstained with Nissl.


RESULTS
We found a negative correlation between the numbers of surviving hilar cells and the duration of the SE (r = -0.66; p < 0.01). In the chronic phase, we could discriminate between rats with occasional seizures (0.15 +/- 0.05 seizures per day) without progression and rats with progressive seizure activity (8.9 +/- 2.8 seizures/day). In both groups, the number of TUNEL-positive cells in parahippocampal regions was similar and higher than in controls. In the hippocampal formation, this was not significantly different from controls. Fluoro-Jade staining showed essentially the same pattern at 1 week and no positive neurons in chronic epileptic rats.


CONCLUSIONS
Cell death in this rat model is related to the initial SE rather than to the frequency of spontaneous seizures. These results emphasize that it is of crucial importance to stop the SE as soon as possible to prevent extended cell loss and further progression of the disease. They also suggest that neuroprotectants can be useful during the first week after SE, but will not be very useful in the chronic epileptic phase.
Gorter
Jan A
JA
Swammerdam Institute for Life Sciences, Section Neurobiology, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands. gorter@science.uva.nl
Gonçalves Pereira
Pedro M
PM
van Vliet
Erwin A
EA
Aronica
Eleonora
E
Lopes da Silva
Fernando H
FH
Lucassen
Paul J
PJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002452:Cell Count; D016923:Cell Death / Q000502:physiology*; D002908:Chronic Disease; D018450:Disease Progression; D004833:Epilepsy, Temporal Lobe / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D009336:Necrosis; D020534:Parahippocampal Gyrus / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D012598:Sclerosis / Q000473:pathology; D013226:Status Epilepticus / Q000473:pathology*