Age-dependent cyclooxygenase-2 induction and neuronal damage after status epilepticus in the postnatal rat hippocampus.
OBJECTIVE
Epileptic seizures lead to age-dependent neuronal damage in the developing brain, particularly in the hippocampus, but the mechanisms involved have remained poorly elucidated. In this study, we investigated the contribution of apoptosis and inflammatory processes to neuronal damage after status epilepticus (SE) in postnatal rats.


METHODS
SE was induced by an intraperitoneal injection of kainic acid (KA) in 21- and 9-day-old (P21 and P9) rats. The expression of Bax, Bcl-2 and caspase-3, markers for apoptosis, and cyclooxygenase-2 (COX-2), an indicator for activation of inflammatory processes, were studied from 6 h up to 1 week after SE by Western blotting and immunocytochemistry. Neuronal damage was verified by Fluoro-Jade B staining.


RESULTS
In P21 rats, SE resulted in neuronal damage in the CA1 neurons of the hippocampus. COX-2 expression was extensively, but transiently, increased and its immunoreactivity pronouncedly enhanced in several hippocampal subregions, amygdala, and piriform cortex by 24 h after SE. The expression of Bax and caspase-3 remained unchanged, whereas the antiapoptotic factor Bcl-2 transiently decreased by 24 h. Single caspase-3 positive neurons appeared in the CA1 region of both control and KA-treated rats. In P9 rats, no neuronal death was detected, and COX-2 expression and immunoreactivity remained at the control level.


CONCLUSIONS
Our results suggest that SE provokes age-specific effects on COX-2 expression. This together with the activation of putative inflammatory processes may contribute to neuronal cell death in the hippocampus of postnatal rats, whereas caspase-dependent apoptosis seems not to be involved in the death process.
Järvelä
Juha T
JT
Department of Pharmacology, Drug Development, and Therapeutics, Institute of Biomedicine, University of Turku, Turku, Finland.
Lopez-Picon
Francisco R
FR
Holopainen
Irma E
IE
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002540:Cerebral Cortex / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism* / Q000502:physiology; D004660:Encephalitis / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004790:Enzyme Induction / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D007608:Kainic Acid; D009474:Neurons / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000201:enzymology; D013226:Status Epilepticus / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D051025:bcl-Associated Death Protein / Q000494:pharmacology
C494821:Bad protein, rat; D051025:bcl-Associated Death Protein; D051546:Cyclooxygenase 2; D053148:Caspase 3; D007608:Kainic Acid