Research paperN-methyl-d-aspartate receptor blockade after status epilepticus protects against limbic brain damage but not against epilepsy in the kainate model of temporal lobe epilepsy
Section snippets
Animals
Adult female Wistar rats (Harlan-Winkelmann, Borchen, Germany; about 12 weeks old) were used. During the experiments the rats were kept under controlled environmental conditions (24–25 °C, 50–60% humidity, 12-h light/dark cycle, light on at 6 a.m.) with free access to standard laboratory chow (Altromin 1324 standard diet) and to tap water. Animal care and all experimental procedures were conducted in compliance with the German Animal Welfare Act and were approved by the local committee on
Kainate-induced S.E
For all experiments described in the following, rats developing a convulsive S.E. with continuous generalized seizure activity for 90 min were used. The S.E. was terminated after 90 min by i.p. injection of 4–6 mg/kg diazepam, which completely stopped clinical (clonic) seizure activity. In order to be sure that diazepam blocked both clinical seizures and persistent electrographic seizure discharges, in some rats continuous video and EEG recording was used to monitor the rats for up to 20 h
Discussion
The present experiments indicate that blockade of the NMDA receptor after a generalized S.E. of sufficient length to produce neuronal damage is an efficacious means to protect several brain regions from such damage. Whereas all rats developed massive neuronal damage in several brain regions after a kainate-induced S.E., administration of a single, low dose of dizocilpine immediately after the S.E. protected several rats almost completely against this damage. The only regions that were not
Acknowledgements
This work was supported by a grant from the German Bundesministerium für Bildung und Forschung (BMBF). We would like to thank U. Heinemann, S. L. Moshé, and R. Schwarcz for critical comments on the manuscript, and M. Weissing, B. Klein and C. Bartling for technical assistance.
References (67)
- et al.
Vigabatrin protects against hippocampal damage but is not antiepileptogenic in the lithium-pilocarpine model of temporal lobe epilepsy
Epilepsy Res
(2001) - et al.
Causes of epilepsycontributions of the Rochester epidemiology project
Mayo Clin Proc
(1996) Limbic seizures and brain damage produced by kainic acidmechanisms and relevance in human temporal lobe epilepsy
Neuroscience
(1985)- et al.
NMDA receptor antagonists and limbic status epilepticusa comparison with standard anticonvulsants
Epilepsy Res
(1990) - et al.
Anticonvulsant action and long-term effects of gabapentin in the immature brain
Neuropharmacology
(2001) - et al.
MK-801 reduced cerebral ischemic injury by inducing hypothermia
Brain Res
(1990) Introduction to temporal lobe epilepsy
Epilepsy Res
(1996)- et al.
Hippocampal sclerosis revisited
Brain Dev
(1998) - et al.
The competitive NMDA receptor antagonist CGP 40116 protects against status epilepticus-induced neuronal damage
Epilepsy Res
(1994) Confusion between neuronal apoptosis and activation of programmed cell death mechanisms in acute necrotic insults
Trends Neurosci
(2000)