Systemic inflammation exacerbates developmental neurotoxicity induced by sevoflurane in neonatal rats.
apoptosis
caspase-1
hippocampus
inflammasome
inflammation
lipopolysaccharide
neonatal anaesthesia
Journal
British journal of anaesthesia
ISSN: 1471-6771
Titre abrégé: Br J Anaesth
Pays: England
ID NLM: 0372541
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
21
09
2021
revised:
14
04
2022
accepted:
08
05
2022
pubmed:
15
6
2022
medline:
6
10
2022
entrez:
14
6
2022
Statut:
ppublish
Résumé
General anaesthesia in the neonatal period has detrimental effects on the developing mammalian brain. The impact of underlying inflammation on anaesthesia-induced developmental neurotoxicity remains largely unknown. Postnatal day 7 (PND7) rats were randomly assigned to receive sevoflurane (3 vol% for 3 h) or carrier gas 12 h after bacterial lipopolysaccharide (LPS; 1 μg g Sevoflurane or LPS treatment increased activated caspase-3 and caspase-9 expression in the hippocampal subiculum and CA1, which was greater when sevoflurane was administered in the setting of LPS-induced inflammation. Neuronal injury induced by LPS+sevoflurane treatment resulted in sex-specific behavioural outcomes when rats were tested at 5-8 weeks of age, including learning and memory deficits in males and heightened anxiety-related behaviour in females. Hippocampal caspase-1 and NLRP1 (NLR family pyrin domain containing 1), but not NLRP3, were upregulated by LPS or LPS+sevoflurane treatment, along with related proinflammatory cytokines, interleukin (IL)-1β, and IL-18. Pretreatment with Vx-765, a selective caspase-1 inhibitor, led to reduced IL-1β in LPS and LPS+sevoflurane groups. Caspase-1 inhibition by Vx-765 significantly decreased activated caspase-3 and caspase-9 immunoreactivity in the subiculum. Systemic inflammation promotes developmental neurotoxicity by worsening anaesthesia-induced neuronal damage with sex-specific behavioural outcomes. This highlights the importance of studying anaesthesia-induced neurotoxicity in more clinically relevant settings.
Sections du résumé
BACKGROUND
General anaesthesia in the neonatal period has detrimental effects on the developing mammalian brain. The impact of underlying inflammation on anaesthesia-induced developmental neurotoxicity remains largely unknown.
METHODS
Postnatal day 7 (PND7) rats were randomly assigned to receive sevoflurane (3 vol% for 3 h) or carrier gas 12 h after bacterial lipopolysaccharide (LPS; 1 μg g
RESULTS
Sevoflurane or LPS treatment increased activated caspase-3 and caspase-9 expression in the hippocampal subiculum and CA1, which was greater when sevoflurane was administered in the setting of LPS-induced inflammation. Neuronal injury induced by LPS+sevoflurane treatment resulted in sex-specific behavioural outcomes when rats were tested at 5-8 weeks of age, including learning and memory deficits in males and heightened anxiety-related behaviour in females. Hippocampal caspase-1 and NLRP1 (NLR family pyrin domain containing 1), but not NLRP3, were upregulated by LPS or LPS+sevoflurane treatment, along with related proinflammatory cytokines, interleukin (IL)-1β, and IL-18. Pretreatment with Vx-765, a selective caspase-1 inhibitor, led to reduced IL-1β in LPS and LPS+sevoflurane groups. Caspase-1 inhibition by Vx-765 significantly decreased activated caspase-3 and caspase-9 immunoreactivity in the subiculum.
CONCLUSIONS
Systemic inflammation promotes developmental neurotoxicity by worsening anaesthesia-induced neuronal damage with sex-specific behavioural outcomes. This highlights the importance of studying anaesthesia-induced neurotoxicity in more clinically relevant settings.
Identifiants
pubmed: 35701270
pii: S0007-0912(22)00246-X
doi: 10.1016/j.bja.2022.05.008
pmc: PMC10080473
pii:
doi:
Substances chimiques
Cytokines
0
Interleukin-18
0
Lipopolysaccharides
0
Sevoflurane
38LVP0K73A
Caspase 3
EC 3.4.22.-
Caspase 9
EC 3.4.22.-
Caspase 1
EC 3.4.22.36
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
555-566Subventions
Organisme : NICHD NIH HHS
ID : R01 HD097990
Pays : United States
Informations de copyright
Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
Références
J Neuroinflammation. 2015 Jun 06;12:114
pubmed: 26048578
Toxicol Sci. 2007 Jul;98(1):145-58
pubmed: 17426105
Nat Commun. 2018 Sep 25;9(1):3916
pubmed: 30254377
Neurobiol Dis. 2012 Feb;45(2):743-50
pubmed: 22075165
Neurotoxicol Teratol. 2011 Mar-Apr;33(2):220-30
pubmed: 21241795
Brain Pathol. 2008 Apr;18(2):198-210
pubmed: 18241241
World J Clin Pediatr. 2015 May 08;4(2):19-24
pubmed: 26015876
J Mol Biol. 2018 Jan 19;430(2):238-247
pubmed: 29100888
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):16012-7
pubmed: 14663141
Pediatr Res. 2007 Sep;62(3):283-90
pubmed: 17551412
Epilepsy Res. 2013 Jan;103(1):2-30
pubmed: 23219031
Mol Neurodegener. 2016 Apr 16;11:28
pubmed: 27084336
J Neuroinflammation. 2010 Jan 29;7:9
pubmed: 20113500
Comp Med. 2008 Apr;58(2):120-8
pubmed: 18524169
J Biol Chem. 2009 Jul 3;284(27):18143-51
pubmed: 19416975
J Neuroinflammation. 2015 Apr 29;12:82
pubmed: 25924675
Glia. 2007 Apr 1;55(5):453-62
pubmed: 17203472
EMBO J. 2019 Sep 2;38(17):e101064
pubmed: 31359456
Cell Death Differ. 2015 Oct;22(10):1676-86
pubmed: 25744023
Neurotoxicol Teratol. 2017 Mar - Apr;60:63-68
pubmed: 27876652
Cell Mol Immunol. 2021 May;18(5):1106-1121
pubmed: 33785842
Br J Anaesth. 2017 Sep 01;119(3):524-531
pubmed: 28969320
J Matern Fetal Neonatal Med. 2017 Nov;30(22):2734-2741
pubmed: 27924651
Neurosci Bull. 2010 Dec;26(6):455-68
pubmed: 21113196
Anesthesiology. 2017 Aug;127(2):227-240
pubmed: 28609302
Anesthesiology. 2009 Mar;110(3):628-37
pubmed: 19212262
Nat Commun. 2019 May 7;10(1):2091
pubmed: 31064994
Neurobiol Dis. 2002 Mar;9(2):205-19
pubmed: 11895372
Br J Anaesth. 2017 Sep 01;119(3):532-540
pubmed: 28969309
Sci Rep. 2016 Apr 20;6:24493
pubmed: 27093924
J Neurosci. 2003 Feb 1;23(3):876-82
pubmed: 12574416
Clin Diagn Lab Immunol. 2005 Jan;12(1):60-7
pubmed: 15642986
Anesthesiology. 2009 Apr;110(4):796-804
pubmed: 19293700
J Neuroimmunol. 2019 Aug 15;333:476962
pubmed: 31108401
Neuroscience. 2005;135(3):815-27
pubmed: 16154281
J Immunol. 2005 May 15;174(10):6195-202
pubmed: 15879116
ChemMedChem. 2010 May 3;5(5):730-8
pubmed: 20229566
Neuroscience. 2008 Apr 9;152(4):959-69
pubmed: 18329814
Anesthesiology. 2012 Jul;117(1):64-71
pubmed: 22617253