Abstract |
In this study the effect of the anti-inflammatory drugs indomethacin, ibuprofen, ebselen (PZ 51, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one), and BW755C (3-amino-1-(m-(trifluoromethyl-phenyl)-2-pyrazoline) on kainic acid (KA)-induced behavioral and neurochemical changes in rats was investigated. Rats injected with KA (10 mg/kg s.c.) developed seizure activity with a 20% mortality within the first 4 h and neuronal degeneration in the limbic system after 3 days. Pretreatment with the cyclooxygenase inhibitor indomethacin (10 mg/kg i.p.) augmented KA-induced epileptic activity and increased the mortality in status epilepticus to 80%. Another cyclooxygenase inhibitor, ibuprofen (20 mg/kg i.p.), and the lipoxygenase inhibitor ebselen (20 mg/kg i.p.) showed no effect on KA-induced symptoms and neurochemical changes. Application of the cyclooxygenase/ lipoxygenase inhibitor BW755C (40 mg/kg i.p.) reduced the severity of seizures and protected significantly from irreversible brain lesions induced by KA. The marked reduction of glutamate decarboxylase (GAD; 53.3 +/- 12.2% of control) and choline acetyltransferase (ChAT; 60.9 +/- 9.1% of control) activities in amygdala/pyriform cortex and GAD activity in hippocampus (69.4 +/- 5.6% of control) observed 3 days after KA injection was abolished by BW755C treatment. Histopathological analyses of brain tissue showed that treatment with BW755C prevented the KA-induced nerve cell degeneration, edema, hemorrhages, and tissue necrosis in amygdala/pyriform cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
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Authors | H Baran, K Vass, H Lassmann, O Hornykiewicz |
Journal | Brain research
(Brain Res)
Vol. 646
Issue 2
Pg. 201-6
(May 23 1994)
ISSN: 0006-8993 [Print] Netherlands |
PMID | 8069664
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Azoles
- Cyclooxygenase Inhibitors
- Isoindoles
- Lipoxygenase Inhibitors
- Organoselenium Compounds
- ebselen
- 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine
- Choline O-Acetyltransferase
- Glutamate Decarboxylase
- Kainic Acid
- Ibuprofen
- Indomethacin
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Topics |
- 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine
(pharmacology)
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology)
- Azoles
(pharmacology)
- Brain
(drug effects, enzymology, pathology)
- Choline O-Acetyltransferase
(metabolism)
- Cyclooxygenase Inhibitors
(pharmacology)
- Glutamate Decarboxylase
(metabolism)
- Ibuprofen
(pharmacology)
- Indomethacin
(pharmacology)
- Isoindoles
- Kainic Acid
(antagonists & inhibitors, toxicity)
- Lipoxygenase Inhibitors
(pharmacology)
- Male
- Organ Specificity
- Organoselenium Compounds
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Seizures
(chemically induced, prevention & control)
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