Neutrophil β
Ischemic Stroke, Neutrophils, I/R, β1AR, Neuroinflammation
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
revised:
10
04
2022
received:
19
05
2021
accepted:
28
04
2022
pubmed:
2
10
2022
medline:
14
1
2023
entrez:
1
10
2022
Statut:
ppublish
Résumé
Reperfusion therapy is the standard of care for ischaemic stroke; however, there is a need to identify new therapeutic targets able to ameliorate cerebral damage. Neutrophil β Rats were subjected to middle cerebral artery occlusion-reperfusion to evaluate the effect on stroke of the selective β1AR blocker metoprolol (12.5 mg·kg Magnetic resonance imaging and histopathology analysis showed that pre-reperfusion i.v. metoprolol reduced infarct size. This effect was accompanied by reduced cytotoxic oedema at 24 h and vasogenic oedema at 7 days. Metoprolol-treated rats showed reduced brain neutrophil infiltration and those which infiltrated displayed a high proportion of anti-inflammatory phenotype (N2, YM1 Our findings describe that β1AR blockade ameliorates cerebral damage by targeting neutrophils, identifying a novel therapeutic target to improve outcomes in patients with stroke. This therapeutic strategy is in the earliest stages of the translational pathway and should be further explored.
Sections du résumé
BACKGROUND AND PURPOSE
Reperfusion therapy is the standard of care for ischaemic stroke; however, there is a need to identify new therapeutic targets able to ameliorate cerebral damage. Neutrophil β
EXPERIMENTAL APPROACH
Rats were subjected to middle cerebral artery occlusion-reperfusion to evaluate the effect on stroke of the selective β1AR blocker metoprolol (12.5 mg·kg
KEY RESULTS
Magnetic resonance imaging and histopathology analysis showed that pre-reperfusion i.v. metoprolol reduced infarct size. This effect was accompanied by reduced cytotoxic oedema at 24 h and vasogenic oedema at 7 days. Metoprolol-treated rats showed reduced brain neutrophil infiltration and those which infiltrated displayed a high proportion of anti-inflammatory phenotype (N2, YM1
CONCLUSIONS AND IMPLICATIONS
Our findings describe that β1AR blockade ameliorates cerebral damage by targeting neutrophils, identifying a novel therapeutic target to improve outcomes in patients with stroke. This therapeutic strategy is in the earliest stages of the translational pathway and should be further explored.
Identifiants
pubmed: 36181002
doi: 10.1111/bph.15963
pmc: PMC10100149
doi:
Substances chimiques
Metoprolol
GEB06NHM23
Receptors, Adrenergic
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
459-478Subventions
Organisme : H2020 European Research Council
ID : ERC-CoG 819775
Organisme : Instituto de Salud Carlos III
ID : MS16/00174
Organisme : Instituto de Salud Carlos III
ID : PI16/02110
Organisme : Instituto de Salud Carlos III
ID : PT20/00044
Organisme : Comunidad de Madrid
ID : 2017-T1/BMD-5185
Organisme : Comunidad de Madrid
ID : S2017/BMD-3867
Organisme : Agencia Estatal de Investigación
ID : PID2019-110369RB-I00
Organisme : Agencia Estatal de Investigación
ID : RYC2020-028884-I
Organisme : Ministerio de Ciencia e Innovación
ID : CEX2020-001041-S
Organisme : Ministerio de Ciencia e Innovación
ID : FPU2017/01932
Organisme : European Research Council
ID : 819775
Pays : International
Informations de copyright
© 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
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