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Open Access 01-12-2017 | Research

Systemic pro-inflammatory cytokine status following therapeutic hypothermia in a piglet hypoxia-ischemia model

Authors: Eridan Rocha-Ferreira, Dorottya Kelen, Stuart Faulkner, Kevin D. Broad, Manigandan Chandrasekaran, Áron Kerenyi, Takenori Kato, Alan Bainbridge, Xavier Golay, Mark Sullivan, Boris W. Kramer, Nicola J. Robertson

Published in: Journal of Neuroinflammation | Issue 1/2017

Abstract

Background

Inflammatory cytokines are implicated in the pathogenesis of perinatal hypoxia-ischemia (HI). The influence of hypothermia (HT) on cytokines after HI is unclear. Our aim was to assess in a piglet asphyxia model, under normothermic (NT) and HT conditions: (i) the evolution of serum cytokines over 48 h and (ii) cerebrospinal fluid (CSF) cytokine levels at 48 h; (iii) serum pro/anti-inflammatory cytokine profile over 48 h and (iv) relation between brain injury measured by magnetic resonance spectroscopy (MRS) and brain TUNEL positive cells with serum cytokines, serum pro/anti-inflammatory cytokines and CSF cytokines.

Methods

Newborn piglets were randomized to NT (n = 5) or HT (n = 6) lasting 2–26 h after HI. Serum samples were obtained 4–6 h before, during and at 6–12 h intervals after HI; CSF was obtained at 48 h. Concentrations of interleukin (IL)-1β, −4, −6, −8, −10 and TNF-α were measured and pro/anti-inflammatory status compared between groups. White matter and thalamic voxel lactate/N-acetyl aspartate (Lac/NAA) (a measure of both oxidative metabolism and neuronal loss) were acquired at baseline, after HI and at 24 and 36 h.

Results

Lac/NAA was reduced at 36 h with HT compared to NT (p = 0.013 basal ganglia and p = 0.033 white matter). HT showed lower serum TNF-α from baseline to 12 h (p < 0.05). Time-matched (acquired within 5 h of each other) serum cytokine and MRS showed correlations between Lac/NAA and serum IL-1β and IL-10 (all p < 0.01). The pro/anti-inflammatory ratios IL-1β/IL-10, IL-6/IL-10, IL-4/IL-10 and IL-8/IL-10 were similar in NT and HT groups until 36 h (24 h for IL-6/IL-10); after this, 36 h pro/anti-inflammatory cytokine ratios in the serum were higher in HT compared to NT (p < 0.05), indicating a pro-inflammatory cytokine surge after rewarming in the HT group. In the CSF at 48 h, IL-8 was lower in the HT group (p < 0.05). At 48 h, CSF TNF-α correlated with Lac/NAA (p = 0.02) and CSF IL-8 correlated with white matter TUNEL positive cell death (p = 0.04).

Conclusions

Following cerebral HI, there was a systemic pro-inflammatory surge after rewarming in the HT group, which is counterintuitive to the putative neuroprotective effects of HT. While serum cytokines were variable, elevations in CSF inflammatory cytokines at 48 h were associated with MRS Lac/NAA and white matter cell death.

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Title: Systemic pro-inflammatory cytokine status following therapeutic hypothermia in a piglet hypoxia-ischemia model
Authors: Eridan Rocha-Ferreira
Dorottya Kelen
Stuart Faulkner
Kevin D. Broad
Manigandan Chandrasekaran
Áron Kerenyi
Takenori Kato
Alan Bainbridge
Xavier Golay
Mark Sullivan
Boris W. Kramer
Nicola J. Robertson
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-017-0821-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Systemic pro-inflammatory cytokine status following therapeutic hypothermia in a piglet hypoxia-ischemia model

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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