Inhaled 45-50% argon augments hypothermic brain protection in a piglet model of perinatal asphyxia

Broad, K, Fierens, I, Fleiss, B, Rocha-Ferreira, E, Ezzati, M, Hassell, J, Alonso-Alconada, D, Bainbridge, A, Kawano, G, Ma, D, Tachtsidis, I, Gressens, P, Golay, X, Sanders, R and Robertson, N 2016, 'Inhaled 45-50% argon augments hypothermic brain protection in a piglet model of perinatal asphyxia', Neurobiology of Disease, vol. 87, pp. 29-38.


Document type: Journal Article
Collection: Journal Articles

Title Inhaled 45-50% argon augments hypothermic brain protection in a piglet model of perinatal asphyxia
Author(s) Broad, K
Fierens, I
Fleiss, B
Rocha-Ferreira, E
Ezzati, M
Hassell, J
Alonso-Alconada, D
Bainbridge, A
Kawano, G
Ma, D
Tachtsidis, I
Gressens, P
Golay, X
Sanders, R
Robertson, N
Year 2016
Journal name Neurobiology of Disease
Volume number 87
Start page 29
End page 38
Total pages 10
Publisher Academic Press
Abstract Cooling to 33.5°C in babies with neonatal encephalopathy significantly reduces death and disability, however additional therapies are needed to maximize brain protection. Following hypoxia-ischemia we assessed whether inhaled 45-50% Argon from 2-26h augmented hypothermia neuroprotection in a neonatal piglet model, using MRS and aEEG, which predict outcome in babies with neonatal encephalopathy, and immunohistochemistry. Following cerebral hypoxia-ischemia, 20 Newborn male Large White piglets<40h were randomized to: (i) Cooling (33°C) from 2-26 h (n=10); or (ii) Cooling and inhaled 45-50% Argon (Cooling+Argon) from 2-26h (n=8). Whole-brain phosphorus-31 and regional proton MRS were acquired at baseline, 24 and 48h after hypoxia-ischemia. EEG was monitored. At 48h after hypoxia-ischemia, cell death (TUNEL) was evaluated over 7 brain regions. There were no differences in body weight, duration of hypoxia-ischemia or insult severity; throughout the study there were no differences in heart rate, arterial blood pressure, blood biochemistry and inotrope support. Two piglets in the Cooling+Argon group were excluded. Comparing Cooling+Argon with Cooling there was preservation of whole-brain MRS ATP and PCr/Pi at 48h after hypoxia-ischemia (p<0.001 for both) and lower1H MRS lactate/N acetyl aspartate in white (p=0.03 and 0.04) but not gray matter at 24 and 48h. EEG background recovery was faster (p<0.01) with Cooling+Argon. An overall difference between average cell-death of Cooling versus Cooling+Argon was observed (p<0.01); estimated cells per mm2were 23.9 points lower (95% C.I. 7.3-40.5) for the Cooling+Argon versus Cooling. Inhaled 45-50% Argon from 2-26h augmented hypothermic protection at 48h after hypoxia-ischemia shown by improved brain energy metabolism on MRS, faster EEG recovery and reduced cell death on TUNEL. Argon may provide a cheap and practical therapy to augment cooling for neonatal encephalopathy.
Subject Neurology and Neuromuscular Diseases
Paediatrics
Keyword(s) Argon
Hypoxia-ischemia
Neonatal encephalopathy
Noble gas
Therapeutic hypothermia
DOI - identifier 10.1016/j.nbd.2015.12.001
Copyright notice © 2016 The Authors.
ISSN 0969-9961
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