Xenon as an adjuvant to therapeutic hypothermia in near-term and term newborns with hypoxic-ischaemic encephalopathy

Rüegger, Christoph M.; Davis, Peter G; Cheong, Jeanie L.Y.

doi:10.1002/14651858.cd012753.pub2

Cited by 20 publications

(18 citation statements)

References 47 publications

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“…Doycheva et al [ 30 ] demonstrated that G-CSF + Ab improved body weight, reduced brain tissue damage, and improved long-term neurological function when assessed at 96 h and 5 weeks post HI in the neonatal rat pups, as well as conferring greater neuroprotection by depleting neutrophil accumulation, while G-CSF + metyrapone treatment not only lower caspase-3 expression level but also reduce corticosterone levels in neonates after HI injury [ 89 ]. Surprisingly, there has not been any study evaluating combinational therapy of G-CSF and therapeutic hypothermia (TH), as other modalities have been tried and underwent and/or are undergoing clinical trials in neonatal HIE, such as with epo and TH [ 120 – 122 ], xenon and TH [ 51 , 123 , 124 ], melatonin and TH [ 46 , 47 ], and allopurinol and TH [ 125 ]. Thus, more study is needed to explore and evaluate the neuroprotective effect of G-CSF in combination with therapeutic hypothermia as well as other emerging agents.…”

Section: Combinational Therapy With Other Agentsmentioning

confidence: 99%

The role of G-CSF neuroprotective effects in neonatal hypoxic-ischemic encephalopathy (HIE): current status

Dumbuya

Chen

et al. 2021

J Neuroinflammation

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Hypoxic-ischemic encephalopathy (HIE) is an important cause of permanent damage to central nervous system (CNS) that may result in neonatal death or manifest later as mental retardation, epilepsy, cerebral palsy, or developmental delay. The primary cause of this condition is systemic hypoxemia and/or reduced cerebral blood flow with long-lasting neurological disabilities and neurodevelopmental impairment in neonates. About 20 to 25% of infants with HIE die in the neonatal period, and 25-30% of survivors are left with permanent neurodevelopmental abnormalities. The mechanisms of hypoxia-ischemia (HI) include activation and/or stimulation of myriad of cascades such as increased excitotoxicity, oxidative stress, N-methyl-d-aspartic acid (NMDA) receptor hyperexcitability, mitochondrial collapse, inflammation, cell swelling, impaired maturation, and loss of trophic support. Different therapeutic modalities have been implicated in managing neonatal HIE, though translation of most of these regimens into clinical practices is still limited. Therapeutic hypothermia, for instance, is the most widely used standard treatment in neonates with HIE as studies have shown that it can inhibit many steps in the excito-oxidative cascade including secondary energy failure, increases in brain lactic acid, glutamate, and nitric oxide concentration. Granulocyte-colony stimulating factor (G-CSF) is a glycoprotein that has been implicated in stimulation of cell survival, proliferation, and function of neutrophil precursors and mature neutrophils. Extensive studies both in vivo and ex vivo have shown the neuroprotective effect of G-CSF in neurodegenerative diseases and neonatal brain damage via inhibition of apoptosis and inflammation. Yet, there are still few experimentation models of neonatal HIE and G-CSF’s effectiveness, and extrapolation of adult stroke models is challenging because of the evolving brain. Here, we review current studies and/or researches of G-CSF’s crucial role in regulating these cytokines and apoptotic mediators triggered following neonatal brain injury, as well as driving neurogenesis and angiogenesis post-HI insults.

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Section: Combinational Therapy With Other Agentsmentioning

confidence: 99%

The role of G-CSF neuroprotective effects in neonatal hypoxic-ischemic encephalopathy (HIE): current status

Dumbuya

Chen

et al. 2021

J Neuroinflammation

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“…For example, Jacobs et al [ 21 ] conducted a Cochrane systematic review of 11 trials (1505 infants) evaluating the effectiveness of therapeutic hypothermia in encephalopathic asphyxiated newborn infants but were unable to analyse several a priori secondary outcomes because these were not reported in the included trials. Likewise, in a review by Ruegger et al [ 32 ] investigating xenon as an adjuvant to therapeutic hypothermia, they judged the risk of attrition bias in the primary outcome as “unclear” due to incomplete outcome reporting. A lack of standardisation in trials limits the ability of researchers and healthcare providers to improve patient treatment and care as any actual benefits or harms of the therapy are not clear due to the substantial differences in outcomes between trials.…”

Section: Introductionmentioning

confidence: 99%

COHESION: core outcomes in neonatal encephalopathy (protocol)

Quirke

Healy

Bhraonáin³

et al. 2021

Trials

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Background Neonatal encephalopathy is a complex syndrome in infants that predominantly affects the brain and other organs. The leading cause is a lack of oxygen in the blood reaching the brain. Neonatal encephalopathy can result in mortality or complications later in life, including seizures, movement disorders and cerebral palsy. Treatment options for neonatal encephalopathy are limited mainly to therapeutic hypothermia, although other potential treatments are emerging. However, evaluations of the effectiveness of treatments are challenging because of heterogeneity and inconsistency in outcomes measured and reported between trials. In this paper, we detail how we will develop a core outcome set to standardise outcomes measured and reported upon for interventions for the treatment of neonatal encephalopathy. Methods We will systematically review the literature to identify outcomes reported previously in randomised trials and systematic reviews of randomised trials. We will identify outcomes important to parents or caregivers of infants diagnosed with and who have received treatment for neonatal encephalopathy. We will do this by conducting in person or by video teleconferencing interviews with parents or caregivers in high-income and low- to middle-income countries. Stakeholders with expertise in neonatal encephalopathy (parents/caregivers, healthcare providers and researchers) will rate the importance of identified outcomes in an online Delphi survey using either a three-round Delphi survey or a “Real-Time” Delphi survey to which stakeholders will be allocated at random. Consensus meetings will take place by video conference to allow for an international group of stakeholder representatives to discuss and vote on the outcomes to include in the final core outcome set (COS). Discussion More research is needed on treatments for neonatal encephalopathy. Standardising outcomes measured and reported in evaluations of the effectiveness of interventions for the treatment of neonatal encephalopathy will improve evidence synthesis and improve results reported in systematic reviews and meta-analysis in this area. Overall, this COS will allow for improved treatments to be identified, heterogeneity in research to be reduced, and overall patient care to be enhanced. Trial registration This study is registered in the Core Outcome Measures for Effectiveness (COMET) database http://www.comet-initiative.org/Studies/Details/1270.

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“…Although treatment with therapeutic hypothermia is an effective approach for neonatal H‐I that is supported by evidence from animal and human studies, the rates of death or disability in these patients are still high (Giesinger et al., 2017; Kali et al., 2015; Shankaran et al., 2017). Combination treatments including therapeutic hypothermia and, for example, melatonin, xenon (targeting the acute injury phase), cannabinoids (targeting the subacute phase), and erythropoietin (targeting the repair phase) have shown considerable potential in their ability to exert neuroprotective effects (Balduini et al., 2019; Ruegger et al., 2018; Solevag et al., 2019; Wu et al., 2016). Further clinical trials reporting neurodevelopmental outcomes are necessary.…”

Section: Potential Therapeutic Strategiesmentioning

confidence: 99%

White matter injury in the neonatal hypoxic‐ischemic brain and potential therapies targeting microglia

Shao

Sun

et al. 2021

J of Neuroscience Research

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Neonatal hypoxic-ischemic (H-I) injury mainly induces neuronal damage and white matter injury (WMI), which are among the predominant causes of death and disability (including cerebral palsy and cognitive and persistent motor deficits) in preterm and term infants. The incidence of neonatal H-I injury or H-I encephalopathy ranges from 1 to 8 per 1,000 live births in developed countries and is as high as 26 per 1,000 live births in developing countries (Kurinczuk et al., 2010). Although therapeutic hypothermia has

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Xenon as an adjuvant to therapeutic hypothermia in near-term and term newborns with hypoxic-ischaemic encephalopathy

Abstract: Current evidence from one small randomised controlled pilot trial is inadequate to show whether cooling plus xenon is safe or effective in near-term and term newborns with HIE. Further trials reporting long-term neurodevelopmental outcomes are needed.

Cited by 20 publications

References 47 publications

The role of G-CSF neuroprotective effects in neonatal hypoxic-ischemic encephalopathy (HIE): current status

The role of G-CSF neuroprotective effects in neonatal hypoxic-ischemic encephalopathy (HIE): current status

COHESION: core outcomes in neonatal encephalopathy (protocol)

White matter injury in the neonatal hypoxic‐ischemic brain and potential therapies targeting microglia

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