Age-dependent cyclooxygenase-2 induction and neuronal damage after status epilepticus in the postnatal rat hippocampus
Juha T. Järvelä,
Francisco R. Lopez-Picon,
Irma E. Holopainen,
Juha T. Järvelä
Department of Pharmacology, Drug Development, and Therapeutics, Institute of Biomedicine, University of Turku, Turku, Finland
Search for more papers by this authorFrancisco R. Lopez-Picon
Department of Pharmacology, Drug Development, and Therapeutics, Institute of Biomedicine, University of Turku, Turku, Finland
Search for more papers by this authorIrma E. Holopainen
Department of Pharmacology, Drug Development, and Therapeutics, Institute of Biomedicine, University of Turku, Turku, Finland
Medicity Research Laboratory, Institute of Biomedicine, University of Turku, FIN-20014 Turku, Finland
Search for more papers by this authorJuha T. Järvelä,
Francisco R. Lopez-Picon,
Irma E. Holopainen,
Juha T. Järvelä
Department of Pharmacology, Drug Development, and Therapeutics, Institute of Biomedicine, University of Turku, Turku, Finland
Search for more papers by this authorFrancisco R. Lopez-Picon
Department of Pharmacology, Drug Development, and Therapeutics, Institute of Biomedicine, University of Turku, Turku, Finland
Search for more papers by this authorIrma E. Holopainen
Department of Pharmacology, Drug Development, and Therapeutics, Institute of Biomedicine, University of Turku, Turku, Finland
Medicity Research Laboratory, Institute of Biomedicine, University of Turku, FIN-20014 Turku, Finland
Search for more papers by this authorAddress correspondence to Dr. Irma Holopainen, M.D., Ph.D., Medicity Research Laboratory, Tykistökatu 6A, 4th floor, University of Turku, FIN-20014 Turku, Finland. E-mail: [email protected].
Summary
Purpose: 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.
Discussion: 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.
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