Abstract |
Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is currently the only FDA-approved drug for acute ischemic stroke. However, its administration is still limited due to the associated increased risk of hemorrhagic transformation (HT). rt-PA may exacerbate blood-brain barrier (BBB) injury by several mechanisms that have not been fully elucidated. Caveolin-1 (Cav-1), a major structural protein of caveolae, has been linked to the endothelial barrier function. The effects of rt-PA on Cav-1 expression remain largely unknown. Here, Cav-1 protein expression after ischemic conditions, with or without rt-PA administration, was analyzed in a murine thromboembolic middle cerebral artery occlusion (MCAO) and in brain microvascular endothelial bEnd.3 cells subjected to oxygen/ glucose deprivation (OGD). Our results show that Cav-1 is overexpressed in endothelial cells of infarcted area and in bEnd.3 cell line after ischemia but there is disagreement regarding rt-PA effects on Cav-1 expression between both experimental models. Delayed rt-PA administration significantly reduced Cav-1 total levels from 24 to 72 h after reoxygenation and increased pCav-1/Cav-1 at 72 h in the bEnd.3 cells while it did not modify Cav-1 immunoreactivity in the infarcted area at 24 h post-MCAO. Importantly, tissue Cav-1 positively correlated with Cav-1 serum levels at 24 h post-MCAO and negatively correlated with the volume of hemorrhage after infarction, the latter supporting a protective role of Cav-1 in cerebral ischemia. In addition, the negative association between baseline serum Cav-1 levels and hemorrhagic volume points to a potential usefulness of baseline serum Cav-1 levels to predict hemorrhagic volume, independently of rt-PA administration.
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Authors | Carme Gubern-Mérida, Pau Comajoan, Gemma Huguet, Isaac García-Yebenes, Ignacio Lizasoain, María Angeles Moro, Irene Puig-Parnau, Juan Manuel Sánchez, Joaquín Serena, Elisabet Kádár, Mar Castellanos |
Journal | Molecular neurobiology
(Mol Neurobiol)
Vol. 59
Issue 2
Pg. 1320-1332
(Feb 2022)
ISSN: 1559-1182 [Electronic] United States |
PMID | 34984586
(Publication Type: Journal Article)
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Copyright | © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. |
Chemical References |
- Cav1 protein, mouse
- Caveolin 1
- Tissue Plasminogen Activator
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Topics |
- Animals
- Brain
(metabolism)
- Brain Ischemia
(metabolism)
- Caveolin 1
(metabolism)
- Endothelial Cells
(metabolism)
- Hemorrhage
(complications)
- Infarction, Middle Cerebral Artery
(complications, drug therapy, metabolism)
- Ischemic Stroke
- Mice
- Stroke
(complications, drug therapy)
- Tissue Plasminogen Activator
(pharmacology, therapeutic use)
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