The highly selective cyclooxygenase-2 inhibitor DFU is neuroprotective when given several hours after transient cerebral ischemia in gerbils

Candelario‐Jalil, Eduardo; Alvarez, Dalia; Castaneda, J. M.; Al-Dalain, S. M.; Martı́nez-Sánchez, Gregorio; Merino, Nelsón; León, Olga Sonia

doi:10.1016/s0006-8993(01)03358-3

Cited by 26 publications

(30 citation statements)

References 22 publications

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“…In vivo studies have found that COX-2 inhibitors decrease the activation of caspase-3 in hippocampal neurons and inflammatory cells (5,29). These findings are similar to ours, namely that a decrease in apoptosis was detected histopathologically in rats given lornoxicam.…”

Section: Discussionsupporting

confidence: 90%

The effects of lornoxicam on neuroprotection following diffuse traumatic brain injury in rats

Topçu

Vatansever²,

Bayram³

et al. 2013

Turkish Neurosurgery

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AIm:In this study, the effects of lornoxicam on the prevention of secondary brain injury via the apoptotic pathway were studied in a rat model of head injury. mAterIAl and methOds: Thirty adult male Wistar albino rats were anesthetized, and experimental closed head trauma was induced by allowing a 450 g weight to fall two meters onto a metallic disk fixed to the intact skull. After head injury, the rats were randomly divided into two groups: Group I (n=15) rats were administered 2 mL saline intraperitoneally (controls); Group II (n=15) rats were administered 2 mL 1.3 mg kg -1 lornoxicam intraperitoneally. Brain tissue samples were divided into two pieces by interhemispheric incision for biochemical and histological analysis. results: TUNEL positivity was seen in neuroglia cells of the brain cortex in both groups. While the immunoreactivities of caspase 8, 9 and Fas/ Fas ligand were similar in both groups, the immunoreactivity of caspase 3 was greater in Group I than Group II. MDA was significantly lower in Group II than in Group I (p<0.05). The decrease in SOD level was higher in Group I than Group II. COnClusIOn:Lornoxicam did not prevent apoptosis in this rat model of brain trauma but causes a decrease.KeywOrds: Traumatic brain injury, Lornoxicam, Apoptosis, Neuroprotection, Rats ÖZ AmAÇ: Bu çalışmada, lornoksikamın sekonder beyin hasarını önlemede, kafa travmalı bir rat modelinde apoptotik yollar aracılı etkileri araştırıldı. yÖntem ve GereÇler: Otuz erişkin Wistar albino rata anestezi uygulaması sonrası kafatası üzerine konan bir metal disk üzerine 2 metreden 450 g ağırlık düşürülerek deneysel kapalı kafa travması oluşturuldu. Travma sonrası ratlar randomize olarak 2 gruba ayrıldı; Grup I'e (n=15) intraperitoneal yolla 2 mL salin, Grup II (n=15) intraperitoneal yolla 2 mL 1.3 mg kg -1 lornoksikam verildi. Beyin dokuları biyokimyasal ve histolojik incelemeler için interhemisferik kesi ile ikiye ayrıldı.BulGulAr: TUNEL pozitifliği her iki grupta beyin korteks nöroglia hücrelerinde görüldü. Her iki grupta kaspaz 8, 9 ve Fas/Fas ligand immünoreaktivitesi normalken, kaspaz 3 immünoreaktivitesi Grup I'de Grup II'den daha yüksekti. MDA Grup II'de Grup I'den daha düşüktü. SOD düzeyindeki azalma Grup I'de, Grup II'den daha fazlaydı. sOnuÇ: Lornoksikam bu beyin travması rat modelimizde apoptozisi önlememiş ancak bir azalma sağlamıştır.

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Section: Discussionsupporting

confidence: 90%

The effects of lornoxicam on neuroprotection following diffuse traumatic brain injury in rats

Topçu

Vatansever²,

Bayram³

et al. 2013

Turkish Neurosurgery

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“…The gerbils were anesthetized with chloral hydrate (300 mg/kg, i.p.) and subjected to transient forebrain ischemia exactly as in our previous reports , 2002Martínez et al, 2001). Briefly, in the supine position, a midline ventral incision was made in the neck.…”

Section: Animals and Surgical Proceduresmentioning

confidence: 83%

“…Briefly, in the supine position, a midline ventral incision was made in the neck. Both common carotid arteries were exposed, separated carefully from the vagus nerve, and occluded for 5 minutes with microaneurysmal clips (Sugita, Japan), which consistently resulted in delayed neuronal death in the CA1 region of the hippocampus (Kirino, 1982;Candelario-Jalil et al, 2002). Blood flow during the occlusion and reperfusion after removal of the clips was visually confirmed and the incision was closed with 4-0 silk sutures.…”

Section: Animals and Surgical Proceduresmentioning

confidence: 99%

“…This treatment schedule was based on our previous experience with another cyclooxygenase-2 inhibitor (Candelario-Jalil et al, 2002). In addition, we reasoned that if cyclooxygenase-2 is one of a select few proteins that still remains upregulated in CA1 neurons even at 3 days after global ischemia (Nakayama et al, 1998;Koistinaho et al, 1999), the nimesulide treatment should be maintained for several days after the ischemic episode.…”

Section: Experiments 1: Dose-response Study Of Nimesulide Treatmentmentioning

confidence: 99%

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Neuroprotective efficacy of nimesulide against hippocampal neuronal damage following transient forebrain ischemia

Candelario‐Jalil

Alvarez

González-Falcón

et al. 2002

European Journal of Pharmacology

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Cyclooxygenase-2 is involved in the inflammatory component of the ischemic cascade, playing an important role in the delayed progression of the brain damage. The present study evaluated the pharmacological effects of the selective cyclooxygenase-2 inhibitor nimesulide on delayed neuronal death of hippocampal CA1 neurons following transient global cerebral ischemia in gerbils.Administration of therapeutically relevant doses of nimesulide (3, 6 and 12 mg/kg; i.p.) 30 minutes before ischemia and at 6, 12, 24, 48 and 72 h after ischemia significantly (P<0.01) reduced hippocampal neuronal damage. Treatment with a single dose of nimesulide given 30 min before ischemia also resulted in a significant increase in the number of healthy neurons in the hippocampal CA1 sector 7 days after ischemia. Of interest is the finding that nimesulide rescued CA1 pyramidal neurons from ischemic death even when treatment was delayed until 24 h after ischemia (34 ± 9 % protection). Neuroprotective effect of nimesulide is still evident 30 days after the ischemic episode, providing the first experimental evidence that cyclooxygenase-2 inhibitors confer a long lasting neuroprotection. Oral administration of nimesulide was also able to significantly reduce brain damage, suggesting that protective effects are independent of the route of administration. The present study confirms the ability of cyclooxygenase-2 inhibitors to reduce brain damage induced by cerebral ischemia and indicates that nimesulide can provide protection when administered for up to 24 h post-ischemia.

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“…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]. The observations that enhanced COX-2 activity contributes to amplify cerebral injury after stroke offer an interesting prospect for targeting the late phase of the damage with COX-2 inhibitors.…”

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

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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

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The highly selective cyclooxygenase-2 inhibitor DFU is neuroprotective when given several hours after transient cerebral ischemia in gerbils

Cited by 26 publications

References 22 publications

The effects of lornoxicam on neuroprotection following diffuse traumatic brain injury in rats

The effects of lornoxicam on neuroprotection following diffuse traumatic brain injury in rats

Neuroprotective efficacy of nimesulide against hippocampal neuronal damage following transient forebrain ischemia

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

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