Neuroprotective and antiepileptogenic effects of combination of anti-inflammatory drugs in the immature brain.

Abstract : ABSTRACT: BACKGROUND: Inflammatory signaling elicited by prolonged seizures can be contributory to neuronal injury as well as adverse plasticity leading to the development of spontaneous recurrent seizures (epilepsy) and associated co-morbidities. In this study, developing rat pups were subjected to lithium-pilocarpine status epilepticus (SE) at 2 and 3 weeks of age to study the effect of anti-inflammatory drugs (AID) on SE-induced hippocampal injury and the development of spontaneous seizures. FINDINGS: We selected AIDs directed against interleukin-1 receptors (IL-1ra), a cyclooxygenase-2 (COX-2) inhibitor (CAY 10404), and an antagonist of microglia activation of caspase-1 (minocycline). Acute injury after SE was studied in the 2-week-old rats 24 h after SE. Development of recurrent spontaneous seizures was studied in 3-week-old rats subjected to SE 4 months after the initial insult.None of those AIDs were effective in attenuating CA1 injury in the 2-week-old pups or in limiting the development of spontaneous seizures in 3-week-old pups when administered individually. When empiric binary combinations of these drugs were tried, the combined targeting of IL-1r and COX-2 resulted in attenuation of acute CA1 injury, as determined 24 h after SE, in those animals. The same combination administered for 10 days following SE in 3-week-old rats, reduced the development of spontaneous recurrent seizures and limited the extent of mossy fiber sprouting. CONCLUSIONS: Deployment of an empirically designed 'drug cocktail' targeting multiple inflammatory signaling pathways for a limited duration after an initial insult like SE may provide a practical approach to neuroprotection and anti-epileptogenic therapy.
Type de document :
Article dans une revue
Journal of Neuroinflammation, BioMed Central, 2013, 10 (1), pp.30. 〈10.1186/1742-2094-10-30〉
Liste complète des métadonnées

Littérature citée [28 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00800959
Contributeur : Ed. Bmc <>
Soumis le : jeudi 14 mars 2013 - 17:09:44
Dernière modification le : mardi 11 octobre 2016 - 14:39:45
Document(s) archivé(s) le : lundi 17 juin 2013 - 12:47:25

Fichiers

Identifiants

Collections

Citation

Young Se Kwon, Eduardo Pineda, Stéphane Auvin, Don Shin, Andrey Mazarati, et al.. Neuroprotective and antiepileptogenic effects of combination of anti-inflammatory drugs in the immature brain.. Journal of Neuroinflammation, BioMed Central, 2013, 10 (1), pp.30. 〈10.1186/1742-2094-10-30〉. 〈inserm-00800959〉

Partager

Métriques

Consultations de la notice

172

Téléchargements de fichiers

112