Edaravone dexborneol regulates γ-aminobutyric acid transaminase in rats with acute intracerebral hemorrhage.
GABA
GABA-T
edaravone dexborneol
intracerebral hemorrhage
neurofilament light chain
neuroinflammation
oxidative stress
Journal
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
ISSN: 1532-8511
Titre abrégé: J Stroke Cerebrovasc Dis
Pays: United States
ID NLM: 9111633
Informations de publication
Date de publication:
01 May 2024
01 May 2024
Historique:
received:
18
04
2023
revised:
22
04
2024
accepted:
27
04
2024
medline:
4
5
2024
pubmed:
4
5
2024
entrez:
3
5
2024
Statut:
aheadofprint
Résumé
Edaravone dexborneol is neuroprotective against ischemic stroke, with free radical-scavenging and anti-inflammatory effects, but its effects in hemorrhagic stroke remain unclear. We evaluated whether edaravone dexborneol has a neuroprotective effect in intracerebral hemorrhage, and its underlying mechanisms. Bioinformatics were used to predict the pathway of action of edaravone dexborneol. An intracerebral hemorrhage model was established using type IV collagenase in edaravone dexborneol, intracerebral hemorrhage, Sham, adeno-associated virus + edaravone dexborneol, and adeno-associated virus + intracerebral hemorrhage groups. The modified Neurological Severity Score was used to evaluate neurological function in rats. Brain water content was measured using the dry-wet weight method. Tumor necrosis factor-α, interleukin-1β, inducible nitric oxide synthase, and γ-aminobutyric acid levels were determined by enzyme-linked immunosorbent assay. The expression levels of neurofilament light chain and γ-aminobutyric acid transaminase were determined by western blot. Nissl staining was used to examine neuronal morphology. Cognitive behavior was evaluated using a small-animal treadmill. Edaravone dexborneol alleviated neurological defects, improved cognitive function, and reduced cerebral edema, neuronal degeneration, and necrosis in rats with cerebral hemorrhage. The expression levels of neurofilament light chain, tumor necrosis factor-α, interleukin-1β, inducible nitric oxide synthase, and γ-aminobutyric acid were decreased, while γ-aminobutyric acid transaminase expression was up-regulated. Edaravone dexborneol regulates γ-aminobutyric acid content by acting on the γ-aminobutyric acid transaminase signaling pathway, thus alleviating oxidative stress, neuroinflammation, neuronal degeneration, and death caused by excitatory toxic injury of neurons after intracerebral hemorrhage.
Identifiants
pubmed: 38701940
pii: S1052-3057(24)00183-6
doi: 10.1016/j.jstrokecerebrovasdis.2024.107738
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
107738Informations de copyright
Copyright © 2024. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors have no potential conflicts of interest to disclose.