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Cited by 13Barrier Structure and Function StudiesAcute Ischemic Stroke ManagementNeurological Disorders and Treatments

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

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Chi, Oak Z., Chiricolo, Antonio, Liu, Xia, Patel, Nikhil, Jacinto, Estela, Weiss, Harvey R.·2021·Neuroscience Letters
DOI 10.1016/j.neulet.2021.136143PMC PMC8434992
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Abstract

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 (K i) of 14 C-α-aminoisobutyric acid, and also determined infarct size, phosphorylation of NDRG1, and MMP2 protein level. Ischemia-reperfusion increased (+34%, p < 0.05) and GSK650394 decreased (-25%, p < 0.05) the K i in the ischemic-reperfused cortex. GSK650394 decreased the percentage of cortical infarct (-31%, p < 0.001). At the same time GSK650394 reduced NDRG1 phosphorylation and MMP2 protein level in the ischemic-reperfused cortex suggesting that SGK1 was inhibited by GSK650394 and that lower MMP2 could be one of the mechanisms of decreased BBB disruption. Collectively our data suggest that GSK650394 could be neuroprotective and one of the mechanisms of the neuroprotection could be decreased BBB disruption. SGK1 inhibition within the thrombolysis therapy time window might reduce cerebral ischemia-reperfusion injury.

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  • After MCAO, inhibiting SGK1 in lateral ventricles of rats within thrombolytic treatment window reduced percentage of cortical infarction and blood-brain barrier disruption.

    “After MCAO, inhibiting SGK1 in the lateral ventricles of rats within the thrombolytic treatment window reduced the percentage of cortical infarction and blood-brain barrier disruption”

    From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Chi et al., 2021

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Cited by

Sorted by citations

Authors
Chi, O. Z., Chiricolo, A., Liu, X., Patel, N., Jacinto, E., & Weiss, H. R.
Affiliations
Rutgers, The State University of New Jersey (US)
Corresponding author
Chi, Oak Z.
ORCID
Venue
Neuroscience Letters
Publisher
Elsevier BV
Published
2021-09
Volume
762
Pages
136143
ISSN
0304-3940 (ISSN-L)
DOI
10.1016/j.neulet.2021.136143
PMC
PMC8434992
OpenAlex
W3186029795
Cited by
13
References
1
Citations by year
2026: 1 · 2025: 1 · 2024: 4 · 2023: 6 · 2022: 1
FWCI
1.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuroscience Letters (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (GM079176, 079176)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
Keywords
SGK1, blood-brain barrier disruption, cerebral ischemia-reperfusion injury, infarct size, MMP-2, neuroprotection, thrombolysis time window, transient middle cerebral artery occlusion
MeSH terms
Serum-Glucocorticoid Regulated Kinases, Animals, Benzoates, Blood-Brain Barrier, Cerebral Infarction, Male, Rats, Inbred F344, Reperfusion Injury, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Neuroprotective Agents, Bridged Bicyclo Compounds, Heterocyclic, Rats

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