Assessing Creatine Supplementation for Neuroprotection against Perinatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review of Perinatal and Adult Pre-Clinical Studies

There is an important unmet need to develop interventions that improve outcomes of hypoxic-ischaemic encephalopathy (HIE). Creatine has emerged as a promising neuroprotective agent. Our objective was to systematically evaluate the preclinical animal studies that used creatine for perinatal neuroprot...

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Autores principales:	Nhi Thao Tran, Sharmony B. Kelly, Rod J. Snow, David W. Walker, Stacey J. Ellery, Robert Galinsky
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	neuroprotection hypoxic ischaemic encephalopathy brain injury perinatal encephalopathy creatine phosphocreatine Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d95d85f385ef44108ce6bd232b2c4dea
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spelling	oai:doaj.org-article:d95d85f385ef44108ce6bd232b2c4dea2021-11-25T17:08:44ZAssessing Creatine Supplementation for Neuroprotection against Perinatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review of Perinatal and Adult Pre-Clinical Studies10.3390/cells101129022073-4409https://doaj.org/article/d95d85f385ef44108ce6bd232b2c4dea2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2902https://doaj.org/toc/2073-4409There is an important unmet need to develop interventions that improve outcomes of hypoxic-ischaemic encephalopathy (HIE). Creatine has emerged as a promising neuroprotective agent. Our objective was to systematically evaluate the preclinical animal studies that used creatine for perinatal neuroprotection, and to identify knowledge gaps that need to be addressed before creatine can be considered for pragmatic clinical trials for HIE. Methods: We reviewed preclinical studies up to 20 September 2021 using PubMed, EMBASE and OVID MEDLINE databases. The SYRCLE risk of bias assessment tool was utilized. Results: Seventeen studies were identified. Dietary creatine was the most common administration route. Cerebral creatine loading was age-dependent with near term/term-equivalent studies reporting higher increases in creatine/phosphocreatine compared to adolescent-adult equivalent studies. Most studies did not control for sex, study long-term histological and functional outcomes, or test creatine post-HI. None of the perinatal studies that suggested benefit directly controlled core body temperature (a known confounder) and many did not clearly state controlling for potential study bias. Conclusion: Creatine is a promising neuroprotective intervention for HIE. However, this systematic review reveals key knowledge gaps and improvements to preclinical studies that must be addressed before creatine can be trailed for neuroprotection of the human fetus/neonate.Nhi Thao TranSharmony B. KellyRod J. SnowDavid W. WalkerStacey J. ElleryRobert GalinskyMDPI AGarticleneuroprotectionhypoxic ischaemic encephalopathybrain injuryperinatal encephalopathycreatinephosphocreatineBiology (General)QH301-705.5ENCells, Vol 10, Iss 2902, p 2902 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	neuroprotection hypoxic ischaemic encephalopathy brain injury perinatal encephalopathy creatine phosphocreatine Biology (General) QH301-705.5
spellingShingle	neuroprotection hypoxic ischaemic encephalopathy brain injury perinatal encephalopathy creatine phosphocreatine Biology (General) QH301-705.5 Nhi Thao Tran Sharmony B. Kelly Rod J. Snow David W. Walker Stacey J. Ellery Robert Galinsky Assessing Creatine Supplementation for Neuroprotection against Perinatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review of Perinatal and Adult Pre-Clinical Studies
description	There is an important unmet need to develop interventions that improve outcomes of hypoxic-ischaemic encephalopathy (HIE). Creatine has emerged as a promising neuroprotective agent. Our objective was to systematically evaluate the preclinical animal studies that used creatine for perinatal neuroprotection, and to identify knowledge gaps that need to be addressed before creatine can be considered for pragmatic clinical trials for HIE. Methods: We reviewed preclinical studies up to 20 September 2021 using PubMed, EMBASE and OVID MEDLINE databases. The SYRCLE risk of bias assessment tool was utilized. Results: Seventeen studies were identified. Dietary creatine was the most common administration route. Cerebral creatine loading was age-dependent with near term/term-equivalent studies reporting higher increases in creatine/phosphocreatine compared to adolescent-adult equivalent studies. Most studies did not control for sex, study long-term histological and functional outcomes, or test creatine post-HI. None of the perinatal studies that suggested benefit directly controlled core body temperature (a known confounder) and many did not clearly state controlling for potential study bias. Conclusion: Creatine is a promising neuroprotective intervention for HIE. However, this systematic review reveals key knowledge gaps and improvements to preclinical studies that must be addressed before creatine can be trailed for neuroprotection of the human fetus/neonate.
format	article
author	Nhi Thao Tran Sharmony B. Kelly Rod J. Snow David W. Walker Stacey J. Ellery Robert Galinsky
author_facet	Nhi Thao Tran Sharmony B. Kelly Rod J. Snow David W. Walker Stacey J. Ellery Robert Galinsky
author_sort	Nhi Thao Tran
title	Assessing Creatine Supplementation for Neuroprotection against Perinatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review of Perinatal and Adult Pre-Clinical Studies
title_short	Assessing Creatine Supplementation for Neuroprotection against Perinatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review of Perinatal and Adult Pre-Clinical Studies
title_full	Assessing Creatine Supplementation for Neuroprotection against Perinatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review of Perinatal and Adult Pre-Clinical Studies
title_fullStr	Assessing Creatine Supplementation for Neuroprotection against Perinatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review of Perinatal and Adult Pre-Clinical Studies
title_full_unstemmed	Assessing Creatine Supplementation for Neuroprotection against Perinatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review of Perinatal and Adult Pre-Clinical Studies
title_sort	assessing creatine supplementation for neuroprotection against perinatal hypoxic-ischaemic encephalopathy: a systematic review of perinatal and adult pre-clinical studies
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d95d85f385ef44108ce6bd232b2c4dea
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Assessing Creatine Supplementation for Neuroprotection against Perinatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review of Perinatal and Adult Pre-Clinical Studies

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