Phenotype Shifting in Astrocytes Account for Benefits of Intra-Arterial Selective Cooling Infusion in Hypertensive Rats of Ischemic Stroke.
Animals
Astrocytes
/ metabolism
Disease Models, Animal
Humans
Hypertension
/ complications
Infarction, Middle Cerebral Artery
/ complications
Ischemic Stroke
Neuroprotective Agents
/ pharmacology
Oxygen
/ metabolism
Phenotype
Rats
Rats, Sprague-Dawley
Stroke
/ metabolism
Tumor Necrosis Factor-alpha
/ metabolism
Astrocytes
Hypertension
Hypothermia
Ischemic stroke
Neuroprotection
Journal
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
ISSN: 1878-7479
Titre abrégé: Neurotherapeutics
Pays: United States
ID NLM: 101290381
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
accepted:
03
01
2022
pubmed:
20
1
2022
medline:
27
5
2022
entrez:
19
1
2022
Statut:
ppublish
Résumé
The translational failure of neuroprotective therapies in stroke may be influenced by the mismatch of existing comorbidities between animal models and patients. Previous studies found that single-target neuroprotective agents reduced infarction in Sprague-Dawley but not in spontaneously hypertensive rats. It is of great interest to explore whether multi-target neuroprotectants and stroke models with comorbidities should be used in further translational researches. Ischemic stroke was induced in normotensive or hypertensive rats by 90- or 120-min middle cerebral artery occlusion (MCAO) and reperfusion. Intra-Arterial Selective Cooling Infusion (IA-SCI) was started at the onset of reperfusion for 30 minutes. Acute neurological deficits, infarct volumes, gene expression and markers of A1-like and A2-like astrocytes were evaluated. In further analysis, TNFα and IL-1α were administrated intracerebroventricularly, phenotype shifting of astrocytes and infarct volumes were assessed. Normobaric oxygen treatment, as a negative control, was also assessed in hypertensive rats. IA-SCI led to similar benefits in normotensive rats with 120-min MCAO and hypertensive rats with both 90-min and 120-min MCAO, including mitigated functional deficit and reduced infarct volumes. IA-SCI shifted astrocyte phenotypes partly by downregulating A1-like astrocytes and upregulating A2-like astrocytes in both RNA and protein levels. Upregulated A1-type astrocyte markers levels, induced by intracerebroventricular injection of TNFα and IL-1α, were closely related to increased infarct volumes in hypertensive rats, despite receiving IA-SCI treatment. In addition, infarct volumes and A1/A2-like genes were not affected by normobaric oxygen treatment. IA-SCI reduced infarction in both normotensive and hypertensive rats. Our results demonstrated the neuroprotective effects of IA-SCI in hypertensive rats may be related with phenotype shifting of astrocytes.
Identifiants
pubmed: 35044645
doi: 10.1007/s13311-022-01186-y
pii: 10.1007/s13311-022-01186-y
pmc: PMC9130426
doi:
Substances chimiques
Neuroprotective Agents
0
Tumor Necrosis Factor-alpha
0
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
386-398Informations de copyright
© 2022. The American Society for Experimental NeuroTherapeutics, Inc.
Références
Lancet. 2018 Oct 6;392(10154):1247-1256
pubmed: 30319112
Stroke. 1989 Jan;20(1):84-91
pubmed: 2643202
Stroke. 2019 Feb;50(2):469-477
pubmed: 30626291
Neuropharmacology. 2018 May 15;134(Pt B):302-309
pubmed: 28830757
Lancet. 2016 Apr 23;387(10029):1723-31
pubmed: 26898852
Eur J Neurosci. 2000 Dec;12(12):4447-56
pubmed: 11122355
Lancet. 2020 Mar 14;395(10227):878-887
pubmed: 32087818
Neurotherapeutics. 2019 Apr;16(2):360-368
pubmed: 30838523
Nat Neurosci. 2019 Feb;22(2):154-166
pubmed: 30664773
J Cereb Blood Flow Metab. 2019 Jul;39(7):1215-1231
pubmed: 30334662
Neuropharmacology. 2000 Mar 3;39(5):777-87
pubmed: 10699444
Nature. 2017 Jan 26;541(7638):481-487
pubmed: 28099414
J Cereb Blood Flow Metab. 2018 Dec;38(12):2251-2260
pubmed: 30019993
J Cereb Blood Flow Metab. 2018 Dec;38(12):2073-2091
pubmed: 30191760
J Cereb Blood Flow Metab. 2021 Jun;41(6):1277-1290
pubmed: 32933360
Stroke. 2018 Jun;49(6):1534-1537
pubmed: 29712880
Neurotherapeutics. 2016 Oct;13(4):685-701
pubmed: 27677607
J Neurosci. 2012 May 2;32(18):6391-410
pubmed: 22553043
J Cereb Blood Flow Metab. 2020 Mar;40(3):461-481
pubmed: 31856639
Endocrinology. 1989 Dec;125(6):3096-102
pubmed: 2573510
J Cereb Blood Flow Metab. 2013 Aug;33(8):1141-7
pubmed: 23736641
Cell Biochem Biophys. 2015 Mar;71(2):637-47
pubmed: 25223242
Stroke. 2015 Feb;46(2):492-9
pubmed: 25563647
Glia. 2008 May;56(7):801-8
pubmed: 18338792
Neurotherapeutics. 2019 Jul;16(3):725-740
pubmed: 30796737
Free Radic Biol Med. 2011 Jul 15;51(2):474-9
pubmed: 21605665
Brain Circ. 2019 Dec 27;5(4):157-159
pubmed: 31950090
Immunity. 2017 Jun 20;46(6):957-967
pubmed: 28636962
Neurosurgery. 2004 Apr;54(4):956-64; discussion 964-5
pubmed: 15046664
Stroke. 2016 Jul;47(7):1933-5
pubmed: 27197848
Circulation. 2020 Mar 3;141(9):e139-e596
pubmed: 31992061
J Cereb Blood Flow Metab. 2022 Jan;42(1):213-215
pubmed: 34670442
J Neurol Neurosurg Psychiatry. 2021 Feb;92(2):129-135
pubmed: 33148815
J Cereb Blood Flow Metab. 2019 Sep;39(9):1693-1709
pubmed: 30461327
Front Aging Neurosci. 2021 Jan 28;13:623751
pubmed: 33584250
Neurotherapeutics. 2020 Oct;17(4):1931-1939
pubmed: 32710291
Stroke. 2020 Feb;51(2):628-636
pubmed: 31884905
Prog Neurobiol. 2016 Sep;144:103-20
pubmed: 26455456
Transl Stroke Res. 2016 Aug;7(4):248-60
pubmed: 27026092