Verapamil inhibits TXNIP-NLRP3 inflammasome activation and preserves functional recovery after intracerebral hemorrhage in mice.
Functional outcome
Intracerebral hemorrhage
NLRP3 inflammasome
TXNIP
Verapamil
Journal
Neurochemistry international
ISSN: 1872-9754
Titre abrégé: Neurochem Int
Pays: England
ID NLM: 8006959
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
03
06
2022
revised:
28
09
2022
accepted:
02
10
2022
pubmed:
17
10
2022
medline:
22
11
2022
entrez:
16
10
2022
Statut:
ppublish
Résumé
Intracerebral hemorrhage (ICH) is the second most common type of stroke with no satisfactory treatment. Recent studies from our group and others indicated a potential positive effect of verapamil, a commonly prescribed calcium channel blocker, with thioredoxin-interacting protein (TXNIP) inhibitor properties, in ischemic stroke and cognitive disorders. It is unclear whether there would be a beneficial effect of verapamil administration in ICH. Therefore, this study was designed to determine the neuroprotective effects of verapamil in a murine ICH model. ICH was induced by stereotactic injection of collagenase type VII (0.075 U) into the right striatum of adult male C57BL/6 mice. Verapamil (0.15 mg/kg) or saline was administered intravenously at 1 h post-ICH followed by oral (1 mg/kg/d) administration in drinking water for 28 days. Motor and cognitive function were assessed using established tests for motor coordination, spatial learning, short- and long-term memory. A subset of animals was sacrificed at 72 h after ICH for molecular analysis. Verapamil treatment reduced expression of TXNIP and NOD-like receptor pyrin domain-containing-3 inflammasome activation in the perihematomal area. These protective effects of verapamil were associated with decreased proinflammatory mediators, microglial activation, and blood-brain barrier permeability markers and paralleled less phosphorylated nuclear factor kappa B level. Our findings also demonstrate that long-term low-dose verapamil effectively attenuated motor and cognitive impairments. Taken together, these data indicate that verapamil has therapeutic potential in improving acute motor function after ICH. Further investigations are needed to confirm whether verapamil treatment could be a promising candidate for clinical trials.
Identifiants
pubmed: 36244583
pii: S0197-0186(22)00148-6
doi: 10.1016/j.neuint.2022.105423
pii:
doi:
Substances chimiques
Inflammasomes
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Verapamil
CJ0O37KU29
Txnip protein, mouse
0
Carrier Proteins
0
Thioredoxins
52500-60-4
Nlrp3 protein, mouse
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
Pagination
105423Subventions
Organisme : NINDS NIH HHS
ID : R01 NS097800
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.