The effects of indomethacin on caspases, glutathione level and lipid peroxidation in the newborn rats with hypoxic-ischemic cerebral injury

Taşkın, Erdal; Özcan, Kenan; Canacankatan, Necmiye; Satar, Mehmet; Yapıcıoğlu, Hacer; Erdoğan, Semra

doi:10.1016/j.brainres.2009.07.010

Cited by 17 publications

(14 citation statements)

References 27 publications

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“…The potential of ibuprofen to be a neuroprotective agent in neonates to stem HI brain injury is further supported by findings that systemic indomethacin or COX-2 inhibitors (NS398) attenuate inflammatory changes as well as functional impairments after neonatal HI in the rodent [142, 144, 145]. In contrast, the effects of NSAIDs on serotonergic neuronal injury after HI are not known.…”

Section: Role Of Neuroinflammation In Producing Neuronal Injurymentioning

confidence: 99%

Disruption of the Serotonergic System after Neonatal Hypoxia-Ischemia in a Rodent Model

Buller

Wixey

Reinebrant

2012

Neurology Research International

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Identifying which specific neuronal phenotypes are vulnerable to neonatal hypoxia-ischemia, where in the brain they are damaged, and the mechanisms that produce neuronal losses are critical to determine the anatomical substrates responsible for neurological impairments in hypoxic-ischemic brain-injured neonates. Here we describe our current work investigating how the serotonergic network in the brain is disrupted in a rodent model of preterm hypoxia-ischemia. One week after postnatal day 3 hypoxia-ischemia, losses of serotonergic raphé neurons, reductions in serotonin levels in the brain, and reduced serotonin transporter expression are evident. These changes can be prevented using two anti-inflammatory interventions; the postinsult administration of minocycline or ibuprofen. However, each drug has its own limitations and benefits for use in neonates to stem damage to the serotonergic network after hypoxia-ischemia. By understanding the fundamental mechanisms underpinning hypoxia-ischemia-induced serotonergic damage we will hopefully move closer to developing a successful clinical intervention to treat neonatal brain injury.

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Section: Role Of Neuroinflammation In Producing Neuronal Injurymentioning

confidence: 99%

Disruption of the Serotonergic System after Neonatal Hypoxia-Ischemia in a Rodent Model

Buller

Wixey

Reinebrant

2012

Neurology Research International

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“…[13,14] Besides its effects on cerebral blood flow and vascular reactivity, indomethacin suppresses the mediators of central nervous system (CNS) inflammation. [12] However, this neuroprotective action [15] has not been verified in all studies. [16] While the COX system is accused of playing an important role in neuroinflammation and neuronal damage leading to cognitive impairments, [17,18] it may also be helpful with regard to its anti-inflammatory activity.…”

Section: Discussionmentioning

confidence: 92%

“…[16] While the COX system is accused of playing an important role in neuroinflammation and neuronal damage leading to cognitive impairments, [17,18] it may also be helpful with regard to its anti-inflammatory activity. [15,18] While controversy on the relationship between neuroprotective effects and different COX subtypes continues, similar debate about the effects of the COX system on cognitive impairment also exists. [16,19] The neuroprotective effects may also be explained by mechanisms other than anti-inflammatory actions, for example mitochondrial depolarization, [20] inhibition of caspase activity along with the reversal of depletion in glutathione, [15] or antithrombotic effects.…”

Section: Discussionmentioning

confidence: 99%

“…[15,18] While controversy on the relationship between neuroprotective effects and different COX subtypes continues, similar debate about the effects of the COX system on cognitive impairment also exists. [16,19] The neuroprotective effects may also be explained by mechanisms other than anti-inflammatory actions, for example mitochondrial depolarization, [20] inhibition of caspase activity along with the reversal of depletion in glutathione, [15] or antithrombotic effects. [21] Because of the absence of neuroinflammation in our study population, cognitive improvement after the administration of indomethacin cannot be addressed.…”

Section: Discussionmentioning

confidence: 99%

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A Single Dose of Indomethacin Does Not Prolong Premotor Reaction Time in Young, Healthy Adults: A Randomized, Placebo-Controlled, Double-Blind, Cross-Over Study

et al. 2012

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Amaç: Bu çalışmada sağlıklı bireylerde tek doz indometazinin bilgi işlem hızını etkileyebileceği hipotezi araştırıldı. Objectives: In this study, we aimed to investigate the hypothesis that a single dose of indomethacin may affect information processing speed in healthy subjects. Hastalar ve yöntemler: Patients and methods:In this cross-sectional, randomized, placebo controlled, double-blind, cross-over study, 30 healthy adults (8 males, 22 females; mean age 32.4±5.3 years; range 24 to 42 years) received a single dose of 25 mg indomethacin (Endol, oral capsule, DEVA Pharmaceutics, Kartepe, Turkey) and placebo. Premotor reaction and response times were measured electromyographically before and after the administration of preparations by a blinded researcher in the Electrophysiology Laboratory at Gazi University, Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Ankara.Results: Premotor reaction time measurements before and after a single dose of indomethacin were 169.1±36.3 and 160.2±29.5 msec, respectively (p=0.113). Premotor reaction time measurements before and after a single dose of placebo were 158.7±35.5 and 161.5±36.3 msec, respectively (p=0.516). There was also no statistically significant difference between premotor reaction time measurements of the indomethacin and placebo groups. Conclusion:A single dose of indomethacin did not change premotor reaction time and response time in healthy adults. This may suggest that indomethacin has no effect on the information processing speed in healthy adults.

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“…Indomethacin, a cyclooxygenase inhibitor, has been shown to reduce neonatal brain damage after perinatal HI in experimental studies [63]. Although indomethacin is currently used in preterm babies to reduce or prevent the occurrence of periventricular/intraventricular hemorrhages [64, 65] and can reduce white matter injury in these tiny infants [66, 67], it has not been used yet in the term infant to reduce reperfusion/reoxygenation injury of the brain after perinatal HI.…”

Section: Pharmacological Neuroprotective Strategiesmentioning

confidence: 99%

Pharmacological Neuroprotection after Perinatal Hypoxic-Ischemic Brain Injury

Fan¹,

Kavelaars²,

Heijnen³

et al. 2010

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Perinatal hypoxia-ischemia (HI) is an important cause of neonatal brain injury. Recent progress in the search for neuroprotective compounds has provided us with several promising drugs to reduce perinatal HI-induced brain injury. In the early stage (first 6 hours after birth) therapies are concentrated on prevention of the production of reactive oxygen species or free radicals (xanthine-oxidase-, nitric oxide synthase-, and prostaglandin inhibition), anti-inflammatory effects (erythropoietin, melatonin, Xenon) and anti-apoptotic interventions (nuclear factor kappa B- and c-jun N-terminal kinase inhibition); in a later stage stimulation of neurotrophic properties in the neonatal brain (erythropoietin, growth factors) can be targeted to promote neuronal and oligodendrocyte regeneration. Combination of pharmacological means of treatment with moderate hypothermia, which is accepted now as a meaningful therapy, is probably the next step in clinical treatment to fight post-asphyxial brain damage. Further studies should be directed at a more rational use of therapies by determining the optimal time and dose to inhibit the different potentially destructive molecular pathways or to enhance endogenous repair while at the same time avoiding adverse effects of the drugs used.

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The effects of indomethacin on caspases, glutathione level and lipid peroxidation in the newborn rats with hypoxic-ischemic cerebral injury

Cited by 17 publications

References 27 publications

Disruption of the Serotonergic System after Neonatal Hypoxia-Ischemia in a Rodent Model

Disruption of the Serotonergic System after Neonatal Hypoxia-Ischemia in a Rodent Model

A Single Dose of Indomethacin Does Not Prolong Premotor Reaction Time in Young, Healthy Adults: A Randomized, Placebo-Controlled, Double-Blind, Cross-Over Study

Pharmacological Neuroprotection after Perinatal Hypoxic-Ischemic Brain Injury

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