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The Selective Cyclooxygenase-2 Inhibitor Rofecoxib Reduces Chronic Cerebral Hypoperfusion-induced Apoptosis in the Rat Hippocampus
Journal of the Korean Neurological Association ; : 660-667, 2002.
Artículo en Coreano | WPRIM | ID: wpr-124506
ABSTRACT

BACKGROUND:

Chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid arteries (2VO) in rats caused cognitive deficits and neuronal damage. Cyclooxygenase-2 (COX-2) inhibitor was reported to attenuate both post-ischemic prostaglandin accumulation and neuronal damage. We studied the expression of mRNA of COX-2 in the hippocampus during hypoperfusion and the effectiveness of selective cyclooxygenase-2 inhibitor, rofecoxib, in preventing the neuronal damage of this model.

METHODS:

Bilateral common carotid arteries of the rat were ligated with silk sutures. The expression of mRNA for COX-1 and COX-2 were detected by the RT-PCR. The first group of animals (n=6) was treated with rofecoxib (10 mg/kg, i.p.) 7 days after operation and the following 7 days. The second group of animals (n=6) was treated with diclofenac sodium (9mg/kg, i.p.) and the third group of animals (n=5) was treated with vehicle (DMSO). TdT-mediated dUTP nick end labeling (TUNEL) technique was performed to estimate delayed cell death.

RESULTS:

Bilateral carotid artery occlusion (2VO) was shown to induce apoptotic morphology and DNA strand break in hippocampal neurons from 7 days with a peak at 14, 28 days. mRNA of COX-2 appeared in the frontal cortex (14, 28 days) and hippocampus (14, 28, 63 days). Treatment with rofecoxib significantly (p<0.05) attenuated the number of TUNEL-labeled cells in the hippocampus, whereas the cells of the diclofenac treated group were not protected.

CONCLUSIONS:

We concluded that COX-2 might contribute to cell death of pyramidal cells of the hippocampus of hypoperfusion and selective COX-2 inhibitor, rofecoxib, could prevent the neuronal damage.
Asunto(s)

Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Suturas / ADN / ARN Mensajero / Demencia Vascular / Arterias Carótidas / Diclofenaco / Muerte Celular / Prostaglandina-Endoperóxido Sintasas / Arteria Carótida Común / Apoptosis Límite: Animales Idioma: Coreano Revista: Journal of the Korean Neurological Association Año: 2002 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Suturas / ADN / ARN Mensajero / Demencia Vascular / Arterias Carótidas / Diclofenaco / Muerte Celular / Prostaglandina-Endoperóxido Sintasas / Arteria Carótida Común / Apoptosis Límite: Animales Idioma: Coreano Revista: Journal of the Korean Neurological Association Año: 2002 Tipo del documento: Artículo