Necroptosis Blockade Potentiates the Neuroprotective Effect of Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy.
HI
HT
MLKL
Nec-1
RIPK
TNF
brain injury
necroptosis
neonatal encephalopathy
neurodisability
neuroinflammation
neuronal death
neuroprotection
therapeutics
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
13 Nov 2022
13 Nov 2022
Historique:
received:
19
10
2022
revised:
08
11
2022
accepted:
11
11
2022
entrez:
26
11
2022
pubmed:
27
11
2022
medline:
27
11
2022
Statut:
epublish
Résumé
Neonatal encephalopathy (NE) caused by hypoxia-ischemia (HI) affects around 1 per 1000 term newborns and is the leading cause of acquired brain injury and neurodisability. Despite the use of hypothermia (HT) as a standard of care, the incidence of NE and its devastating outcomes remains a major issue. Ongoing research surrounding add-on neuroprotective strategies against NE is important as HT effects are limited, leaving 50% of treated patients with neurological sequelae. Little is known about the interaction between necroptotic blockade and HT in neonatal HI. Using a preclinical Lewis rat model of term human NE induced by HI, we showed a neuroprotective effect of Necrostatin-1 (Nec-1: a compound blocking necroptosis) in combination with HT. The beneficial effect of Nec-1 added to HT against NE injuries was observed at the mechanistic level on both pMLKL and TNF-α, and at the anatomical level on brain volume loss visualized by magnetic resonance imaging (MRI). HT alone showed no effect on activated necroptotic effectors and did not preserve the brain MRI volume. This study opens new avenues of research to understand better the specific cell death mechanisms of brain injuries as well as the potential use of new therapeutics targeting the necroptosis pathway.
Identifiants
pubmed: 36428481
pii: biomedicines10112913
doi: 10.3390/biomedicines10112913
pmc: PMC9687213
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : CIHR
ID : 165948
Pays : Canada
Organisme : The foundation of Stars
ID : n/a
Organisme : The Montreal Children's Hospital Foundation
ID : n/a
Organisme : La Région Auvergne-Rhône-Alpes
ID : n/a
Organisme : Université Jean Monnet at Saint-Étienne, France
ID : n/a
Organisme : Brain Canada Foundation
ID : n/a
Organisme : Fonds de Recherche du Québec - Santé
ID : n/a
Références
Dev Neurosci. 2015;37(4-5):407-16
pubmed: 26021410
Clin Transl Immunology. 2017 Jan 06;6(1):e124
pubmed: 28197335
Sci Rep. 2019 Jun 13;9(1):8587
pubmed: 31197179
Pharmacol Res Perspect. 2017 Dec;5(6):
pubmed: 29226626
Croat Med J. 2019 Apr 30;60(2):121-126
pubmed: 31044583
J Cereb Blood Flow Metab. 2016 Jun;36(6):1075-86
pubmed: 26661180
Brain Res. 2015 Dec 10;1629:94-103
pubmed: 26485031
J Neurochem. 2016 Jan;136(1):13-27
pubmed: 26376102
Curr Probl Pediatr Adolesc Health Care. 2019 Jul;49(7):100636
pubmed: 31371100
Biomolecules. 2020 Oct 10;10(10):
pubmed: 33050394
Bioorg Med Chem Lett. 2005 Nov 15;15(22):5039-44
pubmed: 16153840
Sci Rep. 2017 Jul 19;7(1):5818
pubmed: 28724891
Mol Cell. 2014 Nov 20;56(4):481-95
pubmed: 25459880
J Neuroinflammation. 2015 May 30;12:111
pubmed: 26025257
Cell Death Discov. 2021 Apr 14;7(1):79
pubmed: 33854042
Neurotox Res. 2018 Jul;34(1):79-92
pubmed: 29313217
Pediatr Res. 2013 Jan;73(1):18-23
pubmed: 23085819
Cell Rep. 2018 Feb 20;22(8):2066-2079
pubmed: 29466734
J Biol Chem. 2013 Oct 25;288(43):31268-79
pubmed: 24019532
Med Hypotheses. 2020 Nov;144:110295
pubmed: 33254488
Cytokine Growth Factor Rev. 2014 Apr;25(2):167-74
pubmed: 24412261
Neural Plast. 2016;2016:2585230
pubmed: 27042359
PLoS One. 2014 May 06;9(5):e96801
pubmed: 24802416
Neurobiol Dis. 2019 Jul;127:570-581
pubmed: 30981830
Brain Res Dev Brain Res. 1997 Jun 18;100(2):149-60
pubmed: 9205806
Cell Death Dis. 2017 Jun 29;8(6):e2905
pubmed: 28661482
Cell Mol Immunol. 2021 Sep;18(9):2114-2127
pubmed: 34321623
Semin Fetal Neonatal Med. 2021 Oct;26(5):101267
pubmed: 34274259
Int J Dev Neurosci. 2016 Dec;55:1-8
pubmed: 27616300
Proc Natl Acad Sci U S A. 2019 May 14;116(20):9714-9722
pubmed: 31048504
Neurobiol Dis. 2016 Aug;92(Pt A):102-12
pubmed: 26409031
N Engl J Med. 2014 Jul 10;371(2):140-9
pubmed: 25006720
Am J Obstet Gynecol. 2020 Sep;223(3):458-460
pubmed: 32184151
JAMA Pediatr. 2015 Apr;169(4):397-403
pubmed: 25685948
Immunity. 2013 Jan 24;38(1):27-40
pubmed: 23260196
Semin Cell Dev Biol. 2021 Jan;109:114-124
pubmed: 32771377
Nat Rev Neurosci. 2019 Jan;20(1):19-33
pubmed: 30467385
Sci Rep. 2020 Jul 2;10(1):10833
pubmed: 32616806
J Neuroinflammation. 2011 May 20;8:55
pubmed: 21599903
Neuroscience. 2012 Sep 6;219:192-203
pubmed: 22579794
Front Neurol. 2017 Nov 16;8:612
pubmed: 29201015
Int J Dev Neurosci. 2020 Jun;80(4):257-266
pubmed: 32115740
Cell Mol Life Sci. 2016 Jun;73(11-12):2251-67
pubmed: 27048812
Trends Pharmacol Sci. 2017 Mar;38(3):202-225
pubmed: 28126382
Ann Neurol. 2011 May;69(5):743-58
pubmed: 21520238
Front Neurol. 2016 Nov 01;7:192
pubmed: 27847497
Biochem Soc Trans. 2014 Apr;42(2):564-8
pubmed: 24646279
Arch Biochem Biophys. 2020 Nov 30;695:108629
pubmed: 33068524
Nat Rev Drug Discov. 2020 Aug;19(8):553-571
pubmed: 32669658
J Neuroinflammation. 2018 Jul 6;15(1):199
pubmed: 29980212
Antioxidants (Basel). 2020 Sep 21;9(9):
pubmed: 32967335
Exp Neurol. 2017 Sep;295:116-124
pubmed: 28579326
J Mol Cell Cardiol. 2018 May;118:26-35
pubmed: 29524460
Nat Chem Biol. 2005 Jul;1(2):112-9
pubmed: 16408008
Genes Dev. 2013 Aug 1;27(15):1640-9
pubmed: 23913919
Cell Rep. 2015 Mar 24;10(11):1836-49
pubmed: 25801023
Exp Neurol. 2016 May;279:223-231
pubmed: 26980487
Front Neurol. 2015 Sep 14;6:198
pubmed: 26441818
Semin Cell Dev Biol. 2014 Nov;35:14-23
pubmed: 25087983
Curr Neurol Neurosci Rep. 2019 Jan 14;19(2):2
pubmed: 30637551
Front Cell Dev Biol. 2014 Feb 20;2:3
pubmed: 25364712
Early Hum Dev. 2010 Jun;86(6):329-38
pubmed: 20554402
Stroke. 1996 May;27(5):919-25; discussion 926
pubmed: 8623114
Neurochem Res. 2015 Apr;40(4):643-50
pubmed: 25576092
Pediatrics. 2013 Oct;132(4):e952-9
pubmed: 24019409
Liver Transpl. 2019 Jul;25(7):1091-1104
pubmed: 31077562
J Neuroinflammation. 2018 Jul 30;15(1):214
pubmed: 30060742
Neurol Res Int. 2012;2012:257563
pubmed: 22666585
Science. 2016 Aug 5;353(6299):603-8
pubmed: 27493188
J Cereb Blood Flow Metab. 2011 Jan;31(1):178-89
pubmed: 20571523
Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):E8788-E8797
pubmed: 28904096