Low-dose 7,8-Dihydroxyflavone Administration After Status Epilepticus Prevents Epilepsy Development.
Brain-derived neurotrophic factor
Epileptogenesis
Neuronal death
TrkB receptor
Journal
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
ISSN: 1878-7479
Titre abrégé: Neurotherapeutics
Pays: United States
ID NLM: 101290381
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
accepted:
08
09
2022
pubmed:
1
10
2022
medline:
15
12
2022
entrez:
30
9
2022
Statut:
ppublish
Résumé
Temporal lobe epilepsy often manifests months or even years after an initial epileptogenic insult (e.g., stroke, trauma, status epilepticus) and, therefore, may be preventable. However, no such preventive treatment is currently available. Aim of this study was to test an antioxidant agent, 7,8-dihydroxyflavone (7,8-DHF), that is well tolerated and effective in preclinical models of many neurological disorders, as an anti-epileptogenic drug. However, 7,8-DHF also acts as a TrkB receptor agonist and, based on the literature, this effect may imply an anti- or a pro-epileptogenic effect. We found that low- (5 mg/kg), but not high-dose 7,8-DHF (10 mg/kg) can exert strong anti-epileptogenic effects in the lithium-pilocarpine model (i.e., highly significant reduction in the frequency of spontaneous seizures and in the time to first seizure after status epilepticus). The mechanism of these different dose-related effects remains to be elucidated. Nonetheless, considering its excellent safety profile and antioxidant properties, as well as its putative effects on TrkB receptors, 7,8-DHF represents an interesting template for the development of effective and well-tolerated anti-epileptogenic drugs.
Identifiants
pubmed: 36180719
doi: 10.1007/s13311-022-01299-4
pii: 10.1007/s13311-022-01299-4
pmc: PMC9723075
doi:
Substances chimiques
6,7-dihydroxyflavone
0
Antioxidants
0
Flavones
0
Receptor, trkB
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1951-1965Informations de copyright
© 2022. The Author(s).
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