Inflammatory profile in a canine model of hypothermic circulatory arrest.
Animals
Biomarkers
/ cerebrospinal fluid
Brain
/ blood supply
Brain Ischemia
/ cerebrospinal fluid
Circulatory Arrest, Deep Hypothermia Induced
/ adverse effects
Cytokines
/ cerebrospinal fluid
Disease Models, Animal
Dogs
Gene Expression Profiling
Humans
Inflammation Mediators
/ cerebrospinal fluid
Male
Anti-inflammatory cytokines
Biomarkers of neurologic injury
Hypothermic circulatory arrest
Ischemic brain injury
Neuroinflammation
Neurologic injury
Pro-inflammatory cytokines
Journal
The Journal of surgical research
ISSN: 1095-8673
Titre abrégé: J Surg Res
Pays: United States
ID NLM: 0376340
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
23
10
2020
revised:
12
01
2021
accepted:
27
02
2021
pubmed:
12
4
2021
medline:
23
9
2021
entrez:
11
4
2021
Statut:
ppublish
Résumé
Hypothermic circulatory arrest (HCA) is a technique used for complex repair of the aorta, but it can be associated with neurologic morbidity. To better understand the molecular changes that underlie ischemic brain injury, we assessed gene expression and cytokine/chemokine polypeptide concentration in brain tissue and cerebrospinal fluid (CSF) of canines that underwent two hours of HCA. Adult male canines were cannulated peripherally for cardiopulmonary bypass, cooled to 18°C, and arrested for two hours. Animals were euthanized two, eight, or 24 hours post-HCA (n = 8 per group), and their brains were compared to brains from eight normal canines, using gene expression microarray analysis, cytokine assay, and histopathology. Two to eight hours after HCA, pro-inflammatory cytokine mRNAs increased markedly, and gene expression was enriched within signaling pathways related to neuroinflammation or ischemic injury. Concentrations of pro-inflammatory cytokine polypeptides IL-6, IL-8, IL-1β, and CCL2 were very low in normal canine brain, whereas anti-inflammatory IL-10 and TGF-β1 were expressed at moderate levels. Pro-inflammatory cytokine concentrations rose robustly in cerebral tissue and CSF after HCA. IL-6 and IL-8 peaked at eight hours and declined at 24 hours, while IL-1β and CCL2 remained elevated. Concentrations of anti-inflammatory IL-10 and TGF-β1 were maintained after HCA, with a significant increase in TGF-β1 at 24 hours. These cytokines represent potential diagnostic markers for ischemic neurologic injury that could be used to assess neurologic injury in patients undergoing HCA. The cellular mechanisms underlying this pro-inflammatory, ischemic-induced injury represent potential targets for neuroprotection in the future.
Sections du résumé
BACKGROUND
Hypothermic circulatory arrest (HCA) is a technique used for complex repair of the aorta, but it can be associated with neurologic morbidity. To better understand the molecular changes that underlie ischemic brain injury, we assessed gene expression and cytokine/chemokine polypeptide concentration in brain tissue and cerebrospinal fluid (CSF) of canines that underwent two hours of HCA.
MATERIALS AND METHODS
Adult male canines were cannulated peripherally for cardiopulmonary bypass, cooled to 18°C, and arrested for two hours. Animals were euthanized two, eight, or 24 hours post-HCA (n = 8 per group), and their brains were compared to brains from eight normal canines, using gene expression microarray analysis, cytokine assay, and histopathology.
RESULTS
Two to eight hours after HCA, pro-inflammatory cytokine mRNAs increased markedly, and gene expression was enriched within signaling pathways related to neuroinflammation or ischemic injury. Concentrations of pro-inflammatory cytokine polypeptides IL-6, IL-8, IL-1β, and CCL2 were very low in normal canine brain, whereas anti-inflammatory IL-10 and TGF-β1 were expressed at moderate levels. Pro-inflammatory cytokine concentrations rose robustly in cerebral tissue and CSF after HCA. IL-6 and IL-8 peaked at eight hours and declined at 24 hours, while IL-1β and CCL2 remained elevated. Concentrations of anti-inflammatory IL-10 and TGF-β1 were maintained after HCA, with a significant increase in TGF-β1 at 24 hours.
CONCLUSIONS
These cytokines represent potential diagnostic markers for ischemic neurologic injury that could be used to assess neurologic injury in patients undergoing HCA. The cellular mechanisms underlying this pro-inflammatory, ischemic-induced injury represent potential targets for neuroprotection in the future.
Identifiants
pubmed: 33839341
pii: S0022-4804(21)00112-8
doi: 10.1016/j.jss.2021.02.014
pmc: PMC8222109
mid: NIHMS1683145
pii:
doi:
Substances chimiques
Biomarkers
0
Cytokines
0
Inflammation Mediators
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
260-273Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL091541
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR027445
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD079123
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Disclosure None to report.
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