Effects of SC58236, a selective COX-2 inhibitor, on epileptogenesis and spontaneous seizures in a rat model for temporal lobe epilepsy

Holtman, Linda; Vliet, Erwin A. van; Queiroz, Cláudio Marcos Teixeira de; Aronica, Eleonora; Gorter, Jan A.

doi:10.1016/j.eplepsyres.2008.12.006

Cited by 101 publications

(75 citation statements)

References 32 publications

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“…Thus, anti-inflammation by COX-2 inhibition seems to constitute an interesting novel approach for disease modification after brain insults such as SE. However, a study with the COX-2 inhibitor 4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide (SC58236) found no disease-modifying or neuroprotective effect when rats were treated after an electrically induced SE (Holtman et al, 2009 (2009) suggested that the long duration of SE negatively interfered with the outcome of COX-2 inhibition that started within this period. Thus, such technical details are very important when comparing studies on prophylactic drug treatment after SE.…”

Section: Novel Approaches For Antiepileptogenesis In Post-status Epilmentioning

confidence: 99%

Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research

Löscher¹,

Brandt²

2010

Pharmacol Rev

365

366

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Section: Novel Approaches For Antiepileptogenesis In Post-status Epilmentioning

confidence: 99%

Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research

Löscher¹,

Brandt²

2010

Pharmacol Rev

365

366

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“…In mice, prolonged SE induced by pilocarpine causes >25% delayed mortality (11), and is associated with a series of molecular and cellular events in the brain, including neurodegeneration, and selective inflammatory reactions involving reactive microglia and astrocytes (12). Although the underlying cellular and molecular mechanisms are incompletely understood, it is known that the rapidly up-regulated COX-2 after seizures promotes brain inflammation and secondary neurodegeneration (13)(14)(15)(16)(17)(18)(19). We recently showed that COX-2 of neuronal origin was responsible for these effects (19).…”

mentioning

confidence: 99%

Inhibition of the prostaglandin receptor EP2 following status epilepticus reduces delayed mortality and brain inflammation

Jiang

Quan

Ganesh

et al. 2013

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

147

250

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Prostaglandin E2 is now widely recognized to play critical roles in brain inflammation and injury, although the responsible prostaglandin receptors have not been fully identified. We developed a potent and selective antagonist for the prostaglandin E2 receptor subtype EP2, TG6-10-1, with a sufficient pharmacokinetic profile to be used in vivo. We found that in the mouse pilocarpine model of status epilepticus (SE), systemic administration of TG6-10-1 completely recapitulates the effects of conditional ablation of cyclooxygenase-2 from principal forebrain neurons, namely reduced delayed mortality, accelerated recovery from weight loss, reduced brain inflammation, prevention of blood-brain barrier opening, and neuroprotection in the hippocampus, without modifying seizures acutely. Prolonged SE in humans causes high mortality and morbidity that are associated with brain inflammation and injury, but currently the only effective treatment is to stop the seizures quickly enough with anticonvulsants to prevent brain damage. Our results suggest that the prostaglandin receptor EP2 is critically involved in neuroinflammation and neurodegeneration, and point to EP2 receptor antagonism as an adjunctive therapeutic strategy to treat SE.inflammatory cytokine | electroencephalography | epileptogenesis | gliosis | neuronal injury A s a dominant product of cyclooxygenase-2 (COX-2 or PTGS2) in the brain, prostaglandin E2 (PGE 2 ) is emerging as a crucial mediator of many COX-2-driven pathological events in the central nervous system (CNS) (1). PGE 2 acts on four G protein-coupled receptors named EP1, EP2, EP3, and EP4. Among these, the EP2 receptor is widely expressed in the brain and plays important physiologic functions, such as in neuronal plasticity (2, 3). However, recent studies have identified a possible link between EP2 signaling and secondary neurotoxicity in models of chronic inflammation and neurodegeneration (1,(4)(5)(6). In a rodent model of amyotrophic lateral sclerosis, for example, EP2 receptor knockout mice exhibit improved survival, down-regulation of proinflammatory enzymes, and reduced oxidative stress (6).Prolonged status epilepticus (SE) in humans is associated with brain injury and substantial morbidity. Mortality is high during refractory SE that requires general anesthesia (7,8), and the 30-d mortality is about 35-37% for adults who experience at least 60 min of SE (9). Outcome in humans is dependent upon age, etiology, and SE duration (8-10), and currently the only effective treatment is to stop the seizures quickly enough to prevent brain damage (10). Most deaths from nonrefractory SE occur in the 2-wk period after successful treatment rather than during the seizure episode itself (9), pointing to a delayed but cascading set of responsible events. In mice, prolonged SE induced by pilocarpine causes >25% delayed mortality (11), and is associated with a series of molecular and cellular events in the brain, including neurodegeneration, and selective inflammatory reactions involving reactive microglia and a...

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“…On the other hand, in this present study showed that after PTZ-induced seizures damage to hippocampal neurons of the rats were prevented by tenoxicam as previous studies, which were treatment with different COX-2 inhibitors 6,[20][21][22][23][24] . In addition, the results of this present study showed that PTZ-induced seizures were resulted in dark neuron production in the hippocampal regions, as observed by previous studies 25,26 .…”

Section: Discussionmentioning

confidence: 46%

“…Some previous researches showed that the drugs that inhibit COX-2 activity such as nimesulide and indomethacin treatment played an anticonvulsant role and reduced hippocampal cell death in experimental epilepsy models 15,17,18 . Using SC-58125, a specific COX-2 inhibitor, inhibited the upregulation of inflammatory cytokines and reduced COX-2 and PGE2 levels and neuronal apoptosis 20,21,22 . On the contrary, using another selective COX-2 inhibitor NS-398 generated proconvulsant effects and increased neuronal mortality and damage in mice 23 .…”

Section: Discussionmentioning

confidence: 99%

Effect of the cyclooxygenase-2 inhibitor tenoxicam on pentylenetetrazole-induced epileptic seizures in rats

Gümüş¹,

Taşkıran²,

Toptas³

et al. 2017

Cumhuriyet Medical Journal

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SUMMARYObjective: Epilepsy is a short-term paroxysmal disturbances of brain functions observed between sudden, abnormal and hypersynchronization discharges and seizures of a group of neurons in the central nervous system. The nonsteroidal anti-inflammatory tenoxicam is chemical agent that selectively inhibits type 2 cyclooxygenase (COX2), which converts arachidonic acid to prostaglandins (PGs). The aim of this study was to investigate the effect of the cyclooxygenase-2 inhibitor tenoxicam on pentylenetetrazole on epileptic seizures. Method: Eighteen Wistar Albino male rats (220±20 g) were divided into three groups: control (n=6), 10 mg/kg/day tenoxicam (n=6) and, 20 mg/kg/day tenoxicam (n=6). Tenoxicam was administered intramuscularly for ten days. On the tenth day, pentylenetetrazol (PTZ) was injected intraperitoneally at 70 mg/kg after 45 minutes of drug administration and the animals were observed for 30 min. Stages were determined according to the Racine seizure scale (RC) and the first myoclonic jerk time (FMJ) was recorded in seconds. After completing procedure, whole brain tissues were removed and stained with toluidine blue stain. The number of dark neurons with chromatin aggregation in hypocampal CA1 and dentate gyrus (DG) was determined as percentage. Results: Epileptic behavior were evaluated according to the RC, 10 mg/kg of tenoxicam significantly reduced the seizure stage compared to the control (p<0,05). In addition, 10 mg/kg tenoxicam significantly increased the FMJ compared to the control (p<0,05). According to the histopathological findings, neuronal damage was increased in CA1 region of 20 mg/kg of tenoxicam group compared to control, whereas neuronal damage was reduced significantly in the dentate gyrus of 10 mg/kg and 20 mg/kg of tenoxicam groups (p<0,05). Conclusions: This study shows that dose-dependent administration of tenoxicam might have a potential to reduce epileptic seizures and post-seizure neuron damage. Keywords: Epilepsy, cyclooxygenase-2 inhibitor, tenoxicam, pentylenetetrazole ÖZET Amaç: Epilepsi merkezi sinir sisteminde bir grup nöronun ani, anormal ve hipersenkronize deşarjları ile nöbetler halinde gözlenen beyin fonksiyonlarının kısa süreli paroksimal rahatsızlığı olarak tanımlanır. Nonsteroid anti inflamatuarlardan olan tenoksikam araşidonik asidi prostaglandinlere dönüştüren tip 2 siklooksijenaz (COX2) 653 enzimini selektif olarak inhibe eden kimyasal bir ajandır. Bu çalışmanın amacı siklooksijenaz-2 inhibitörü tenoksikam'ın pentilentetrazol ile oluşturulan epileptik nöbetlere üzerine etkisini araştırmaktır. Yöntem: Çalışmamızda 18 tane 220-240 gr Wistar Albino erkek sıçan kullanılmıştır. Hayvanlar kontrol (n=6), 10 mg/kg/gün tenoksikam (n=6) ve 20 mg/kg/gün tenoksikam (n=6) olmak üzere üç gruba ayrıldı. On gün süre ile kontrol grubuna çözücü ve diğer iki gruba belirtilen dozlarda tenoksikam intramusküler olarak uygulandı. Onuncu gün ilaç uygulamalarından 45 dk sonra pentilentetrazol (PTZ) 70 mg/kg intraperitoneal olarak enjekte edildi. Hayvanlar 30 dk boyunca gözlemlendi....

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Effects of SC58236, a selective COX-2 inhibitor, on epileptogenesis and spontaneous seizures in a rat model for temporal lobe epilepsy

Cited by 101 publications

References 32 publications

Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research

Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research

Inhibition of the prostaglandin receptor EP2 following status epilepticus reduces delayed mortality and brain inflammation

Effect of the cyclooxygenase-2 inhibitor tenoxicam on pentylenetetrazole-induced epileptic seizures in rats

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