Effects of Lithium Ions on tPA-Induced Hemorrhagic Transformation under Stroke

Thrombolytic therapy with the tissue plasminogen activator (tPA) is a therapeutic option for acute ischemic stroke. However, this approach is subject to several limitations, particularly the increased risk of hemorrhagic transformation (HT). Lithium salts show neuroprotective effects in stroke, but...

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Published inBiomedicines Vol. 12; no. 6; p. 1325
Main Authors Babenko, Valentina A., Yakupova, Elmira I., Pevzner, Irina B., Bocharnikov, Alexey D., Zorova, Ljubava D., Fedulova, Kseniya S., Grebenchikov, Oleg A., Kuzovlev, Artem N., Grechko, Andrey V., Silachev, Denis N., Rahimi-Moghaddam, Parvaneh, Plotnikov, Egor Y.
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 01.06.2024
MDPI
Subjects
Blood-brain barrier
Brain damage
Cell activation
Endothelial cells
Endothelium
Gelatinase A
Glucose
Glycolysis
Hemorrhage
hemorrhagic transformation
Ischemia
Laboratory animals
Lithium
Lithium chloride
lithium salts
Magnetic resonance imaging
Neurological diseases
Neuroprotection
Oxygen
oxygen-glucose deprivation
photothrombosis
Stroke
t-Plasminogen activator
Thrombolysis
Tissue plasminogen activator
Russia
France
United States > US
tissue plasminogen activator
hemorrhagic transformation
oxygen-glucose deprivation
photothrombosis
lithium salts
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Summary:Thrombolytic therapy with the tissue plasminogen activator (tPA) is a therapeutic option for acute ischemic stroke. However, this approach is subject to several limitations, particularly the increased risk of hemorrhagic transformation (HT). Lithium salts show neuroprotective effects in stroke, but their effects on HT mechanisms are still unknown. In our study, we use the models of photothrombosis (PT)-induced brain ischemia and oxygen-glucose deprivation (OGD) to investigate the effect of Li+ on tPA-induced changes in brain and endothelial cell cultures. We found that tPA did not affect lesion volume or exacerbate neurological deficits but disrupted the blood–brain barrier. We demonstrate that poststroke treatment with Li+ improves neurological status and increases blood–brain barrier integrity after thrombolytic therapy. Under conditions of OGD, tPA treatment increased MMP-2/9 levels in endothelial cells, and preincubation with LiCl abolished this MMP activation. Moreover, we observed the effect of Li+ on glycolysis in tPA-treated endothelial cells, which we hypothesized to have an effect on MMP expression.
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These authors contributed equally to this work.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines12061325