Ibuprofen inhibits neuroinflammation and attenuates white matter damage following hypoxia–ischemia in the immature rodent brain

Carty, Michelle L.; Wixey, Julie A.; Reinebrant, Hanna E.; Gobé, Glenda C.; Colditz, Paul B.; Buller, Kathryn M.

doi:10.1016/j.brainres.2011.06.001

Cited by 49 publications

(34 citation statements)

References 74 publications

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“…Consistent with previous studies [86, 139–142], we have shown that COX-2 is elevated in the brain after P3 HI and that ibuprofen significantly prevents this effect as well as P3 HI-induced increases in numbers of activated microglia, IL-1 β , and TNF- α levels [143]. In association with these anti-inflammatory effects ibuprofen ameliorated reductions in cerebral hemisphere size, O4-positive pre-myelinating, O1-positive immature oligodendrocyte cell counts, and myelin content [143]. …”

Section: Role Of Neuroinflammation In Producing Neuronal Injurysupporting

confidence: 92%

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 Injurysupporting

confidence: 92%

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

Buller

Wixey

Reinebrant

2012

Neurology Research International

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“…Despite some positive effects on neurons,64,65 neuroinflammation is mainly involved in HI-induced cell death 66. Different anti-inflammatory strategies have been shown to provide neuroprotection in models of perinatal HI injury 67–69. The anti-inflammatory properties of Lf are thus possible causes of the neuroprotection.…”

Section: Discussionmentioning

confidence: 99%

Lactoferrin during lactation protects the immature hypoxic‐ischemic rat brain

Looij

Ginet

Chatagner

et al. 2014

Ann Clin Transl Neurol

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ObjectiveLactoferrin (Lf) is an iron-binding glycoprotein secreted in maternal milk presenting anti-inflammatory and antioxidant properties. It shows efficient absorption into the brain from nutritional source. Brain injury frequently resulting from cerebral hypoxia-ischemia (HI) has a high incidence in premature infants with ensuing neurodevelopmental disabilities. We investigated the neuroprotective effect of maternal nutritional supplementation with Lf during lactation in a rat model of preterm HI brain injury using magnetic resonance imaging (MRI), brain gene, and protein expression.MethodsModerate brain HI was induced using unilateral common carotid artery occlusion combined with hypoxia (6%, 30 min) in the postnatal day 3 (P3) rat brain (24–28 weeks human equivalent). High-field multimodal MRI techniques were used to investigate the effect of maternal Lf supplementation through lactation. Expression of cytokine coding genes (TNF-α and IL-6), the prosurvival/antiapoptotic AKT protein and caspase-3 activation were also analyzed in the acute phase after HI.ResultsMRI analysis demonstrated reduced cortical injury in Lf rats few hours post-HI and in long-term outcome (P25). Lf reduced HI-induced modifications of the cortical metabolism and altered white matter microstructure was recovered in Lf-supplemented rats at P25. Lf supplementation significantly decreased brain TNF-α and IL-6 gene transcription, increased phosphorylated AKT levels and reduced activation of caspase-3 at 24 h post-injury.InterpretationLf given through lactation to rat pups with cerebral HI injury shows neuroprotective effects on brain metabolism, and cerebral gray and white matter recovery. This nutritional intervention may be of high interest for the clinical field of preterm brain neuroprotection.

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“…Neuroinflammation is promoted by cyclooxygenase-2 (COX-2) (2), and the activity of COX-2 can be inhibited by non-steroidal anti-inflammatory drugs (NSAIDs) (3, 4). NSAIDs have prolonged survival in transgenic mouse models of ALS (5, 6), but results from a clinical trial did not find a protective effect of the selective COX-2 inhibitor Celecoxib on ALS disease progression (7).…”

Section: Introductionmentioning

confidence: 99%

Non-steroidal anti-inflammatory drugs and amyotrophic lateral sclerosis: Results from five prospective cohort studies

Fondell

O’Reilly

Fitzgerald

et al. 2012

Amyotrophic Lateral Sclerosis

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Objective Animal and pathological studies suggest that inflammation may contribute to amyotrophic lateral sclerosis (ALS) pathology and that non-steroidal anti-inflammatory drugs (NSAIDs) might be protective. However, there are no prospective data on the relation between NSAID use and ALS risk in humans. Methods The relation between NSAID use and ALS risk was explored in five large prospective cohort studies (the Nurses’ Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health – AARP Diet and Health Study). Detailed NSAID information was sought from 780,000 participants, 708 of whom developed ALS during follow-up. Cox proportional hazards models were used within each cohort and cohort-specific estimates were pooled with random effects models. Results Neither non-aspirin NSAID use, nor aspirin use was associated with ALS risk overall. The multivariable, pooled relative risk was 0.96 (95% CI 0.76-1.22) among non-aspirin NSAID users compared with non-users. Duration of NSAID use in years and frequency of NSAID use were not associated with ALS risk overall. Conclusion The results do not support an overall effect of NSAIDs on ALS risk, but because NSAIDs have heterogeneous effects, a role of individual compounds cannot be excluded.

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Ibuprofen inhibits neuroinflammation and attenuates white matter damage following hypoxia–ischemia in the immature rodent brain

Cited by 49 publications

References 74 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

Lactoferrin during lactation protects the immature hypoxic‐ischemic rat brain

Non-steroidal anti-inflammatory drugs and amyotrophic lateral sclerosis: Results from five prospective cohort studies

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