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.
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Authors | Young Se Kwon, Eduardo Pineda, Stéphane Auvin, Don Shin, Andrey Mazarati, Raman Sankar |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 10
Pg. 30
(Feb 26 2013)
ISSN: 1742-2094 [Electronic] England |
PMID | 23442201
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Anticonvulsants
- Neuroprotective Agents
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Topics |
- Animals
- Animals, Newborn
- Anti-Inflammatory Agents, Non-Steroidal
(administration & dosage)
- Anticonvulsants
(administration & dosage)
- Brain
(drug effects, pathology)
- Drug Therapy, Combination
- Neuroprotective Agents
(administration & dosage)
- Rats
- Rats, Wistar
- Status Epilepticus
(pathology, prevention & control)
- Treatment Outcome
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