Inhibition of serum and glucocorticoid regulated kinases by GSK650394 reduced infarct size in early cerebral ischemia-reperfusion with decreased BBB disruption

[Display omitted] •Inhibition of SGK1 decreased infarct in early cerebral ischemia-reperfusion.•Inhibition of SGK1 decreased BBB disruption in early cerebral reperfusion.•Decreased MMP2 by GSK650394 could be one of the mechanisms of the BBB protection.•Inhibition of SGK1 may be neuroprotective withi...

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Published in:Neuroscience letters 2021-09, Vol.762, p.136143-136143, Article 136143
Main Authors: Chi, Oak Z., Chiricolo, Antonio, Liu, Xia, Patel, Nikhil, Jacinto, Estela, Weiss, Harvey R.
Format: Article
Language:English
Subjects:
Animals
Benzoates - pharmacology
Blood-brain barrier
Blood-Brain Barrier - drug effects
Blood-Brain Barrier - pathology
Brain protection
Bridged Bicyclo Compounds, Heterocyclic - pharmacology
Cerebral Infarction - pathology
Cerebral ischemia-reperfusion
GSK650394
Immediate-Early Proteins - antagonists & inhibitors
Male
Neuroprotective Agents - pharmacology
Protein Serine-Threonine Kinases - antagonists & inhibitors
Rats
Rats, Inbred F344
Reperfusion Injury - pathology
SGK1
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Summary:[Display omitted] •Inhibition of SGK1 decreased infarct in early cerebral ischemia-reperfusion.•Inhibition of SGK1 decreased BBB disruption in early cerebral reperfusion.•Decreased MMP2 by GSK650394 could be one of the mechanisms of the BBB protection.•Inhibition of SGK1 may be neuroprotective within the first few hours of stroke. Blood-brain barrier (BBB) disruption is one of the most important pathological changes following cerebral ischemia-reperfusion. We tested whether inhibition of the serum and glucocorticoid regulated kinase 1 (SGK1) would decrease BBB disruption and contribute to decreasing infarct size in the first few hours of cerebral ischemia-reperfusion within the thrombolysis therapy time window. After transient middle cerebral artery occlusion (MCAO), an SGK1 inhibitor GSK650394, or vehicle was administered into the lateral ventricle of rats. After one hour of MCAO and two hours of reperfusion, we determined BBB disruption using the transfer coefficient (Ki) of 14C-α-aminoisobutyric acid, and also determined infarct size, phosphorylation of NDRG1, and MMP2 protein level. Ischemia-reperfusion increased (+34%, p 
ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2021.136143