Verapamil inhibits TXNIP-NLRP3 inflammasome activation and preserves functional recovery after intracerebral hemorrhage in mice.


Journal

Neurochemistry international
ISSN: 1872-9754
Titre abrégé: Neurochem Int
Pays: England
ID NLM: 8006959

Informations de publication

Date de publication:
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

105423

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS097800
Pays : United States

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Auteurs

Saifudeen Ismael (S)

Department of Anatomy and Neurobiology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA.

Devlin Patrick (D)

Department of Anatomy and Neurobiology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA; Department of Acute and Tertiary Care, College of Nursing, University of Tennessee Health Science Center, Memphis, TN, USA.

Mohd Salman (M)

Department of Anatomy and Neurobiology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA.

Arshi Parveen (A)

Department of Anatomy and Neurobiology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA.

Ansley Grimes Stanfill (AG)

Department of Acute and Tertiary Care, College of Nursing, University of Tennessee Health Science Center, Memphis, TN, USA; Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

Tauheed Ishrat (T)

Department of Anatomy and Neurobiology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA; Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: tishrat@uthsc.edu.

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Classifications MeSH