IL-1β Antibody Protects Brain from Neuropathology of Hypoperfusion.
Animals
Behavior, Animal
/ drug effects
Body Weight
/ drug effects
Brain
/ blood supply
Brain Ischemia
/ pathology
Cerebrovascular Circulation
/ drug effects
Gray Matter
/ drug effects
Interleukin-1beta
/ pharmacology
Male
Mice, Inbred C57BL
Neuroprotective Agents
/ pharmacology
White Matter
/ drug effects
IL-1β
IL-1β antibody
canakinumab
cerebral hypoperfusion
white matter damage and grey matter damage
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
09 04 2021
09 04 2021
Historique:
received:
10
03
2021
revised:
02
04
2021
accepted:
06
04
2021
entrez:
30
4
2021
pubmed:
1
5
2021
medline:
21
10
2021
Statut:
epublish
Résumé
Chronic brain hypoperfusion is the primary cause of vascular dementia and has been implicated in the development of white matter disease and lacunar infarcts. Cerebral hypoperfusion leads to a chronic state of brain inflammation with immune cell activation and production of pro-inflammatory cytokines, including IL-1β. In the present study, we induced chronic, progressive brain hypoperfusion in mice using ameroid constrictor, arterial stenosis (ACAS) surgery and tested the efficacy of an IL-1β antibody on the resulting brain damage. We observed that ACAS surgery causes a reduction in cerebral blood flow (CBF) of about 30% and grey and white matter damage in and around the hippocampus. The IL-1β antibody treatment did not significantly affect CBF but largely eliminated grey matter damage and reduced white matter damage caused by ACAS surgery. Over the course of hypoperfusion/injury, grip strength, coordination, and memory-related behavior were not significantly affected by ACAS surgery or antibody treatment. We conclude that antibody neutralization of IL-1β is protective from the brain damage caused by chronic, progressive brain hypoperfusion.
Identifiants
pubmed: 33918659
pii: cells10040855
doi: 10.3390/cells10040855
pmc: PMC8069995
pii:
doi:
Substances chimiques
Interleukin-1beta
0
Neuroprotective Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIA NIH HHS
ID : T32 AG052375
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM109098
Pays : United States
Organisme : National Science Foundation
ID : 1916894
Organisme : NIH HHS
ID : P20GM103434
Pays : United States
Organisme : American Heart Association
ID : 16SDG31170008
Organisme : NIGMS NIH HHS
ID : U54 GM104942
Pays : United States
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