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New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy

Around 0.75 million babies worldwide suffer from moderate or severe hypoxic-ischemic encephalopathy (HIE) each year resulting in around 400,000 babies with neurodevelopmental impairment. In 2010, neonatal HIE was associated with 2.4% of the total Global Burden of Disease. Therapeutic hypothermia (TH...

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Autores principales: Victor, Suresh, Rocha-Ferreira, Eridan, Rahim, Ahad, Hagberg, Henrik, Edwards, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897336/
https://www.ncbi.nlm.nih.gov/pubmed/34820702
http://dx.doi.org/10.1007/s00431-021-04320-8
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author Victor, Suresh
Rocha-Ferreira, Eridan
Rahim, Ahad
Hagberg, Henrik
Edwards, David
author_facet Victor, Suresh
Rocha-Ferreira, Eridan
Rahim, Ahad
Hagberg, Henrik
Edwards, David
author_sort Victor, Suresh
collection PubMed
description Around 0.75 million babies worldwide suffer from moderate or severe hypoxic-ischemic encephalopathy (HIE) each year resulting in around 400,000 babies with neurodevelopmental impairment. In 2010, neonatal HIE was associated with 2.4% of the total Global Burden of Disease. Therapeutic hypothermia (TH), a treatment that is now standard of care in high-income countries, provides proof of concept that strategies that aim to improve neurodevelopment are not only possible but can also be implemented to clinical practice. While TH is beneficial, neonates with moderate or severe HIE treated with TH still experience devastating complications: 48% (range: 44–53) combined death or moderate/severe disability. There is a concern that TH may not be effective in low- and middle-income countries. Therapies that further improve outcomes are desperately needed, and in high-income countries, they must be tested in conjunction with TH. We have in this review focussed on pharmacological treatment options (e.g. erythropoietin, allopurinol, melatonin, cannabidiol, exendin-4/exenatide). Erythropoietin and allopurinol show promise and are progressing towards the clinic with ongoing definitive phase 3 randomised placebo-controlled trials. However, there remain global challenges for the next decade.  Conclusion: There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials to avoid exposure to harmful medications or abandoning putative treatments.
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spelling pubmed-88973362022-03-08 New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy Victor, Suresh Rocha-Ferreira, Eridan Rahim, Ahad Hagberg, Henrik Edwards, David Eur J Pediatr Review Around 0.75 million babies worldwide suffer from moderate or severe hypoxic-ischemic encephalopathy (HIE) each year resulting in around 400,000 babies with neurodevelopmental impairment. In 2010, neonatal HIE was associated with 2.4% of the total Global Burden of Disease. Therapeutic hypothermia (TH), a treatment that is now standard of care in high-income countries, provides proof of concept that strategies that aim to improve neurodevelopment are not only possible but can also be implemented to clinical practice. While TH is beneficial, neonates with moderate or severe HIE treated with TH still experience devastating complications: 48% (range: 44–53) combined death or moderate/severe disability. There is a concern that TH may not be effective in low- and middle-income countries. Therapies that further improve outcomes are desperately needed, and in high-income countries, they must be tested in conjunction with TH. We have in this review focussed on pharmacological treatment options (e.g. erythropoietin, allopurinol, melatonin, cannabidiol, exendin-4/exenatide). Erythropoietin and allopurinol show promise and are progressing towards the clinic with ongoing definitive phase 3 randomised placebo-controlled trials. However, there remain global challenges for the next decade.  Conclusion: There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials to avoid exposure to harmful medications or abandoning putative treatments. Springer Berlin Heidelberg 2021-11-24 2022 /pmc/articles/PMC8897336/ /pubmed/34820702 http://dx.doi.org/10.1007/s00431-021-04320-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review
Victor, Suresh
Rocha-Ferreira, Eridan
Rahim, Ahad
Hagberg, Henrik
Edwards, David
New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy
title New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy
title_full New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy
title_fullStr New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy
title_full_unstemmed New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy
title_short New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy
title_sort new possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897336/
https://www.ncbi.nlm.nih.gov/pubmed/34820702
http://dx.doi.org/10.1007/s00431-021-04320-8
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