Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model

Robertson, N, Faulkner, S, Fleiss, B, Bainbridge, A, Andorka, C, Price, D, Powell, E, Lecky-Thompson, L, Thei, L, Chandrasekaran, M, Hristova, M, Cady, E, Gressens, P, Golay, X and Raivich, G 2013, 'Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model', Brain, vol. 136, pp. 90-105.


Document type: Journal Article
Collection: Journal Articles

Title Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model
Author(s) Robertson, N
Faulkner, S
Fleiss, B
Bainbridge, A
Andorka, C
Price, D
Powell, E
Lecky-Thompson, L
Thei, L
Chandrasekaran, M
Hristova, M
Cady, E
Gressens, P
Golay, X
Raivich, G
Year 2013
Journal name Brain
Volume number 136
Start page 90
End page 105
Total pages 16
Publisher Oxford University Press
Abstract Despite treatment with therapeutic hypothermia, almost 50% of infants with neonatal encephalopathy still have adverse outcomes. Additional treatments are required to maximize neuroprotection. Melatonin is a naturally occurring hormone involved in physiological processes that also has neuroprotective actions against hypoxic-ischaemic brain injury in animal models. The objective of this study was to assess neuroprotective effects of combining melatonin with therapeutic hypothermia after transient hypoxia-ischaemia in a piglet model of perinatal asphyxia using clinically relevant magnetic resonance spectroscopy biomarkers supported by immunohistochemistry. After a quantified global hypoxic-ischaemic insult, 17 newborn piglets were randomized to the following: (i) therapeutic hypothermia (33.5°C from 2 to 26 h after resuscitation, n = 8) and (ii) therapeutic hypothermia plus intravenous melatonin (5 mg/kg/h over 6 h started at 10 min after resuscitation and repeated at 24 h, n = 9). Cortical white matter and deep grey matter voxel proton and whole brain (31)P magnetic resonance spectroscopy were acquired before and during hypoxia-ischaemia, at 24 and 48 h after resuscitation. There was no difference in baseline variables, insult severity or any physiological or biochemical measure, including mean arterial blood pressure and inotrope use during the 48 h after hypoxia-ischaemia. Plasma levels of melatonin were 10 000 times higher in the hypothermia plus melatonin than hypothermia alone group. Melatonin-augmented hypothermia significantly reduced the hypoxic-ischaemic-induced increase in the area under the curve for proton magnetic resonance spectroscopy lactate/N-acetyl aspartate and lactate/total creatine ratios in the deep grey matter. Melatonin-augmented hypothermia increased levels of whole brain (31)P magnetic resonance spectroscopy nucleotide triphosphate/exchangeable phosphate pool. Correlating with improved cerebral energy metabolism, TUNEL-positive nuclei were re
Subject Innate Immunity
Paediatrics
Neurology and Neuromuscular Diseases
Keyword(s) hypoxiaischaemia
therapeutic hypothermia
neuroprotection
melatonin
neonatal encephalopathy
DOI - identifier 10.1093/brain/aws285
Copyright notice © The Author (2012)
ISSN 0006-8950
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