Epilepsy Research (2009) 84, 56—66
journal homepage: www.elsevier.com/locate/epilepsyres
Effects of SC58236, a selective COX-2 inhibitor, on
epileptogenesis and spontaneous seizures in a rat
model for temporal lobe epilepsy
L. Holtman
a
, E.A. van Vliet
a,c
, R. van Schaik
a
, C.M. Queiroz
a
,
E. Aronica
b,c
, J.A. Gorter
a,c,*
a
Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Kruislaan 320, 1098 SM,
Amsterdam, The Netherlands
b
Academic Medical Center, Department of (Neuro) Pathology, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam,
The Netherlands
c
Epilepsy Institute in The Netherlands (SEIN), Achterweg 5, 2103 SW, Heemstede, The Netherlands
Received 4 November 2008; received in revised form 18 December 2008; accepted 22 December 2008
Available online 30 January 2009
KEYWORDS
Status epilepticus;
Anti-inflammatory;
In vivo;
Immunocytochemistry;
Human;
Prostaglandin;
EEG;
Seizures
Summary Inflammation is an important biological process that is activated after status epilep-
ticus and could be implicated in the development of epilepsy. Here we tested whether an
anti-inflammatory treatment with a selective cox-2 inhibitor (SC58236) could prevent the devel-
opment of epilepsy or modify seizure activity during the chronic epileptic phase. SC58236 was
orally administered (10 mg/kg) during the latent period for 7 days, starting 4 h after electri-
cally induced SE. Seizures were monitored using EEG/video monitoring until 35 days after SE.
Cell death and inflammation were investigated using immunocytochemistry (NeuN and Ox-42).
Sprouting was studied using Timm’s staining after 1 week and after 4—5 months when rats
were chronic epileptic. SC58236 was also administered during 5 days in chronic epileptic rats.
Hippocampal EEG seizures were continuously monitored before, during and after treatment.
SC58236 effectively reduced PGE
2
production but did not modify seizure development or the
extent of cell death or microglia activation in the hippocampus. SC58236 treatment in chronic
epileptic rats did not show any significant change in seizure duration or frequency of daily
seizures. The fact that cox-2 inhibition, which effectively reduced prostaglandin levels, did not
modify epileptogenesis or chronic seizure activity suggests that this type of treatment (starting
after SE) will not provide an effective anti-epileptogenic or anti-epileptic therapy.
© 2008 Elsevier B.V. All rights reserved.
∗
Corresponding author at: Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Kruislaan 320,
1098 SM, Amsterdam, The Netherlands. Tel.: +31 20 5257893; fax: +31 20 5257709.
E-mail address: j.a.gorter@uva.nl (J.A. Gorter).
0920-1211/$ — see front matter © 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.eplepsyres.2008.12.006