Cyclo-oxygenase-2 Messenger RNA Induction in Focal Cerebral Ischemia

Colląo-Moraes, Yolanda; Aspey, B. S.; Harrison, Michael J.; Belleroche, Jacqueline de

doi:10.1097/00004647-199611000-00035

Cited by 126 publications

(64 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Arachidonic acid is converted into eicosanoids with a concomitant production of superoxide by cyclooxygenases and 5-lipooxygenase (Kontos, 1987;Krause et al, 1988). An increased expression and activation of COX-2 was observed in neurons and glial cells in rodent and human ischemic brains (Planas et al, 1995;Collaco-Moraes et al, 1996;Sairanen et al, 1998). They were shown to depend upon activation of NMDA receptors in neurons (Miettinen et al, 1997).…”

Section: Metabolism Of Arachidonic Acidmentioning

confidence: 98%

Cellular and Molecular Pathways of Ischemic Neuronal Death

Won¹,

Kim²,

Gwag³

2002

BMB Reports

201

172

View full text Add to dashboard Cite

Three routes have been identified triggering neuronal death under physiological and pathological conditions. Excess activation of ionotropic glutamate receptors cause influx and accumulation of Ca 2+ and Na + that result in rapid swelling and subsequent neuronal death within a few hours. The second route is caused by oxidative stress due to accumulation of reactive oxygen and nitrogen species. Apoptosis or programmed cell death that often occurs during developmental process has been coined as additional route to pathological neuronal death in the mature nervous system. Evidence is being accumulated that excitotoxicity, oxidative stress, and apoptosis propagate through distinctive and mutually exclusive signal transduction pathway and contribute to neuronal loss following hypoxic-ischemic brain injury. Thus, the therapeutic intervention of hypoxic-ischemic neuronal injury should be aimed to prevent excitotoxicity, oxidative stress, and apoptosis in a concerted way.

show abstract

Section: Metabolism Of Arachidonic Acidmentioning

confidence: 98%

Cellular and Molecular Pathways of Ischemic Neuronal Death

Won¹,

Kim²,

Gwag³

2002

BMB Reports

201

172

View full text Add to dashboard Cite

show abstract

“…COX-2 mRNA and protein levels have shown to be significantly increased within neurons and vascular cells in both experimental animal models of cerebral ischemia [15,21,38,43,50,51,55,61] and in infarcted human brain [35,60]. Moreover, administration of highly selective COX-2 inhibitors has been proven to reduce brain damage and prostaglandin accumulation following cerebral ischemia [9][10][11][12]50,51].…”

Section: Introductionmentioning

confidence: 99%

Wide therapeutic time window for nimesulide neuroprotection in a model of transient focal cerebral ischemia in the rat

et al. 2004

View full text Add to dashboard Cite

Results from several studies indicate that cyclooxygenase-2 (COX-2) is involved ischemic brain injury. The purpose of this study was to evaluate the neuroprotective effects of the selective COX-2 inhibitor nimesulide on cerebral infarction and neurological deficits in a standardized model of transient focal cerebral ischemia in rats. Three doses of nimesulide (3, 6 and 12 mg/kg; i.p.) or vehicle were administered immediately after stroke and additional doses were given at 6, 12, 24, 36 and 48 h after ischemia. In other set of experiments, the effect of nimesulide was studied in a situation in which its first administration was delayed for 3 to 24 h after ischemia.Total, cortical and subcortical infarct volumes and functional outcome (assessed by neurological deficit score and rotarod performance) were determined 3 days after ischemia. The effect of nimesulide on prostaglandin E 2 (PGE 2 ) levels in the injured brain was also investigated.Nimesulide dose-dependently reduced infarct volume and improved functional recovery when compared to vehicle. Of interest is the finding that neuroprotection conferred by nimesulide (reduction of infarct size and neurological deficits and improvement of rotarod performance) was also observed when treatment was delayed until 24 h after ischemia. Further, administration of nimesulide in a delayed treatment paradigm completely abolished PGE 2 accumulation in the postischemic brain, suggesting that COX-2 inhibition is a promising therapeutic strategy for cerebral ischemia to target the late-occurring inflammatory events which amplify initial damage. Theme: Disorders of the nervous systemTopic: Ischemia

show abstract

“…It is normally expressed throughout the brain in discrete populations of neurons and is regulated by glutamate receptors and glucocorticoids (9)(10)(11). Recently, seizure (12) and brain ischemia (13) were reported to induce COX-2 mRNA or protein.…”

mentioning

confidence: 99%

Spreading depression and focal brain ischemia induce cyclooxygenase-2 in cortical neurons through N -methyl- d -aspartic acid-receptors and phospholipase A ₂

Miettinen

Fusco

Yrjänheikki

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

271

170

View full text Add to dashboard Cite

Repetitive spreading depression (SD) waves, involving depolarization of neurons and astrocytes and upregulation of glucose consumption, is thought to lower the threshold of neuronal death during and immediately after ischemia. Using rat models for SD and focal ischemia we investigated the expression of cyclooxygenase-1 (COX-1), the constitutive form, and cyclooxygenase-2 (COX-2), the inducible form of a key enzyme in prostaglandin biosynthesis and the target enzymes for nonsteroidal anti-inf lammatory drugs. Whereas COX-1 mRNA levels were undetectable and uninducible, COX-2 mRNA and protein levels were rapidly increased in the cortex, especially in layers 2 and 3 after SD and transient focal ischemia. The cortical induction was reduced by MK-801, an N-methyl-D-aspartic acid-receptor antagonist, and by dexamethasone and quinacrine, phospholipase A 2 (PLA 2 ) inhibiting compounds. MK-801 acted by blocking SD whereas treatment with PLA 2 inhibitors preserved the wave propagation. NBQX, an ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid͞kainate-receptor antagonist, did not affect the SD-induced COX-2 expression, whereas COXinhibitors indomethacin and diclofenac, as well as a NO synthase-inhibitor, N G -nitro-L-arginine methyl ester, tended to enhance the COX-2 mRNA expression. In addition, ischemia induced COX-2 expression in the hippocampal and perifocal striatal neurons and in endothelial cells. Thus, COX-2 is transiently induced after SD and focal ischemia by activation of N-methyl-D-aspartic acid-receptors and PLA 2 , most prominently in cortical neurons that are at a high risk to die after focal brain ischemia.

show abstract

Cyclo-oxygenase-2 Messenger RNA Induction in Focal Cerebral Ischemia

Cited by 126 publications

References 45 publications

Cellular and Molecular Pathways of Ischemic Neuronal Death

Cellular and Molecular Pathways of Ischemic Neuronal Death

Wide therapeutic time window for nimesulide neuroprotection in a model of transient focal cerebral ischemia in the rat

Spreading depression and focal brain ischemia induce cyclooxygenase-2 in cortical neurons through N -methyl- d -aspartic acid-receptors and phospholipase A ₂

Contact Info

Product

Resources

About

Cyclo-oxygenase-2 Messenger RNA Induction in Focal Cerebral Ischemia

Cited by 126 publications

References 45 publications

Cellular and Molecular Pathways of Ischemic Neuronal Death

Cellular and Molecular Pathways of Ischemic Neuronal Death

Wide therapeutic time window for nimesulide neuroprotection in a model of transient focal cerebral ischemia in the rat

Spreading depression and focal brain ischemia induce cyclooxygenase-2 in cortical neurons through N -methyl- d -aspartic acid-receptors and phospholipase A 2

Contact Info

Product

Resources

About

Spreading depression and focal brain ischemia induce cyclooxygenase-2 in cortical neurons through N -methyl- d -aspartic acid-receptors and phospholipase A ₂