Opposite caudal versus rostral brain nitric oxide synthase response to generalized seizures in a novel rodent model of reflex epilepsy.
OBJECTIVE
Nitric oxide (NO) is synthesized from L-arginine (L-Arg) by three different isoforms of NO synthase (NOS), i.e. the constitutive neuronal and endothelial NOS (nNOS and eNOS) and the inducible NOS (iNOS). NO has been involved in the pathophysiology of epilepsy, but available data are conflicting and the actual role of NO in epilepsy still remains to be clarified. In this study we investigated the basal and post-seizure levels of constitutive NOS (cNOS) activity as well as the expression of the cNOS isoforms across brain regions in a novel model of epilepsy.


METHODS
cNOS activity was assessed in various brain areas along the rostro-caudal axis in control wild type hamsters, unstimulated generalized audiogenic seizure prone hamsters, Salamanca strain, GASH:Sal and GASH:Sal after 10 sound-induced epileptic seizures. Additionally, Western blot experiments for nNOS and eNOS were performed in those areas where relevant changes in cNOS activity were found.


RESULTS
In the GASH:Sal, cNOS activity increased in the mesencephalic areas studied while cNOS activity decreased in both the striatum and cerebral cortex after 10 sound-induced epileptic seizures. nNOS (but not eNOS) expression paralleled the variations in cNOS activity. The same sound stimulation had no effect on control hamsters.


CONCLUSIONS
These results suggest a different NOS response in the regions close to the original epileptic focus (caudal, in our auditory model) versus the remote areas (rostral) possibly recruited at later stages or after repeated crises. These findings may account for some of the discrepancies found regarding the role of NO in epilepsy.
Neuropsychopharmacology Unit, University General Hospital of Albacete, 37 Hermanos Falcó Street, Albacete E-02006, Spain. anaprima05@hotmail.com
Ana I
AI
Prieto-Martín
Silvia
S
Llorens
José Manuel
JM
Pardal-Fernández
Luis J
LJ
Muñoz
Dolores E
DE
López
Julio
J
Escribano
Eduardo
E
Nava
Carlos
C
de Cabo
D000818:Animals; D001120:Arginine / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000201:enzymology* / Q000503:physiopathology*; D006224:Cricetinae; D004195:Disease Models, Animal; D020195:Epilepsy, Reflex / Q000201:enzymology* / Q000503:physiopathology*; D007527:Isoenzymes / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D012640:Seizures / Q000503:physiopathology*
D007527:Isoenzymes; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase