Neuroprotective and antiepileptogenic effects of combination of anti-inflammatory drugs in the immature brain. - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Journal of Neuroinflammation Year : 2013

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.
Fichier principal
Vignette du fichier
1742-2094-10-30.pdf (463.64 Ko) Télécharger le fichier
1742-2094-10-30.xml (45.72 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Format : Other
Loading...

Dates and versions

inserm-00800959 , version 1 (14-03-2013)

Identifiers

Cite

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, 2013, 10 (1), pp.30. ⟨10.1186/1742-2094-10-30⟩. ⟨inserm-00800959⟩

Collections

INSERM UNIV-PARIS7
105 View
138 Download

Altmetric

Share

Gmail Facebook X LinkedIn More