Abstract |
Injection of kainic acid (KA) into the brain causes severe seizures with hippocampal neuron loss. KA has been shown to immediately induce cyclooxygenase-2 (COX-2) expression in hippocampal neurons, indicating that neuronal COX-2 might be involved in neuronal death. In this study, however, we reveal that the delayed COX-2 induction in non-neuronal cells after KA injection plays an important role in hippocampal neuron loss rather than early COX-2 expression in neurons. We find that KA microinjection into the hemilateral hippocampus shows a later induction of COX-2 expression in non-neuronal cells, such as endothelial cells and astrocytes. In the KA-injected side, PGE2 concentration gradually increases and peaks at 24 h after injection, when non-neuronal COX-2 expression also peaks. When this delayed PGE2 elevation is prevented by selective COX-2 inhibitor NS398, it can block hippocampal cell death. Moreover, COX-2 knockout mice are also resistant to neuronal death after KA treatment. These findings indicate that delayed PGE2 production by non-neuronal COX-2 may facilitate neuronal death after seizure. Inhibition of COX-2 to an extent similar to PGE2 elevation after onset of seizure may be useful to prevent neuronal death.
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Authors | Takako Takemiya, Michiyo Maehara, Kiyoshi Matsumura, Shin Yasuda, Hiroko Sugiura, Kanato Yamagata |
Journal | Neuroscience research
(Neurosci Res)
Vol. 56
Issue 1
Pg. 103-10
(Sep 2006)
ISSN: 0168-0102 [Print] Ireland |
PMID | 16837093
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cyclooxygenase Inhibitors
- Excitatory Amino Acid Agonists
- Nitrobenzenes
- Sulfonamides
- N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
- Cyclooxygenase 2
- Dinoprostone
- Kainic Acid
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Topics |
- Animals
- Cell Death
(physiology)
- Cyclooxygenase 2
(genetics, metabolism)
- Cyclooxygenase Inhibitors
(metabolism)
- Dinoprostone
(metabolism)
- Enzyme Induction
- Excitatory Amino Acid Agonists
(pharmacology)
- Hippocampus
(cytology, drug effects)
- Kainic Acid
(pharmacology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Microinjections
- Neurons
(cytology, drug effects, physiology)
- Nitrobenzenes
(metabolism)
- Rats
- Rats, Wistar
- Seizures
(chemically induced, metabolism)
- Sulfonamides
(metabolism)
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