Inhibition of p70 ribosomal S6 kinase 1 (S6K1) by PF-4708671 decreased infarct size in early cerebral ischemia-reperfusion with decreased BBB permeability.
Animals
Blood-Brain Barrier
/ drug effects
Enzyme Inhibitors
/ pharmacology
Hemodynamics
/ drug effects
Imidazoles
/ pharmacology
Infarction, Middle Cerebral Artery
/ complications
Male
Permeability
/ drug effects
Phosphorylation
/ drug effects
Piperazines
/ pharmacology
Rats
Reperfusion Injury
/ complications
Ribosomal Protein S6 Kinases
/ antagonists & inhibitors
Signal Transduction
/ drug effects
Time Factors
(14)C-α-aminoisobutyric acid
Blood-brain barrier
Brain protection
Cerebral ischemia-reperfusion
PF-4708671
S6K1 inhibitor
Journal
European journal of pharmacology
ISSN: 1879-0712
Titre abrégé: Eur J Pharmacol
Pays: Netherlands
ID NLM: 1254354
Informations de publication
Date de publication:
15 Jul 2019
15 Jul 2019
Historique:
received:
23
12
2018
revised:
01
05
2019
accepted:
03
05
2019
pubmed:
8
5
2019
medline:
21
12
2019
entrez:
8
5
2019
Statut:
ppublish
Résumé
It is not clear whether inhibition of p70 ribosomal S6 kinase 1 (S6K1) is neuroprotective in cerebral ischemia-reperfusion. Decreasing blood-brain barrier (BBB) disruption has been associated with a better neuronal outcome in cerebral ischemia. We hypothesized that inhibition of S6K1 would decrease BBB disruption and infarct size in the early stage of cerebral ischemia-reperfusion. Middle cerebral artery occlusion (MCAO) was performed in rats under isoflurane anesthesia with controlled ventilation. 75 mg/kg of PF-4708671, an S6K1 inhibitor, was administered intraperitoneally 15 min after MCAO. After 1 h of MCAO and 2 h of reperfusion, the transfer coefficient (K
Identifiants
pubmed: 31063769
pii: S0014-2999(19)30314-0
doi: 10.1016/j.ejphar.2019.05.010
pii:
doi:
Substances chimiques
Enzyme Inhibitors
0
Imidazoles
0
PF-4708671
0
Piperazines
0
Ribosomal Protein S6 Kinases
EC 2.7.11.1
Rps6kb1 protein, rat
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
202-207Informations de copyright
Copyright © 2019. Published by Elsevier B.V.