Spatiotemporal sphingosine-1-phosphate receptor 3 expression within the cerebral vasculature after ischemic stroke
(2024) In iScience 27(6).- Abstract
Sphingosine-1-phosphate receptors (S1PRs) are promising therapeutic targets in cardiovascular disease, including ischemic stroke. However, important spatiotemporal information for alterations of S1PR expression is lacking. Here, we investigated the role of S1PR3 in ischemic stroke in rodent models and patient samples. We show that S1PR3 is acutely upregulated in perilesional reactive astrocytes after stroke, and that stroke volume and behavioral deficits are improved in mice lacking S1PR3. Further, we find that administration of an S1PR3 antagonist at 4-h post-stroke, but not at later timepoints, improves stroke outcome. Lastly, we observed higher plasma S1PR3 concentrations in experimental stroke and in patients with ischemic stroke.... (More)
Sphingosine-1-phosphate receptors (S1PRs) are promising therapeutic targets in cardiovascular disease, including ischemic stroke. However, important spatiotemporal information for alterations of S1PR expression is lacking. Here, we investigated the role of S1PR3 in ischemic stroke in rodent models and patient samples. We show that S1PR3 is acutely upregulated in perilesional reactive astrocytes after stroke, and that stroke volume and behavioral deficits are improved in mice lacking S1PR3. Further, we find that administration of an S1PR3 antagonist at 4-h post-stroke, but not at later timepoints, improves stroke outcome. Lastly, we observed higher plasma S1PR3 concentrations in experimental stroke and in patients with ischemic stroke. Together, our results establish S1PR3 as a potential drug target and biomarker in ischemic stroke.
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- author
- Matuskova, Hana LU ; Porschen, Lisa T. LU ; Matthes, Frank LU ; Lindgren, Arne G. LU ; Petzold, Gabor C. and Meissner, Anja LU
- organization
- publishing date
- 2024-06-21
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Biological sciences, Molecular neuroscience, Natural sciences, Neuroscience, Pathophysiology, Physiology
- in
- iScience
- volume
- 27
- issue
- 6
- article number
- 110031
- publisher
- Elsevier
- external identifiers
-
- scopus:85194360267
- ISSN
- 2589-0042
- DOI
- 10.1016/j.isci.2024.110031
- language
- English
- LU publication?
- yes
- id
- 6e077bbf-cb03-4cc3-b418-43a4ed959ca8
- date added to LUP
- 2024-08-14 15:24:40
- date last changed
- 2024-08-14 15:25:17
@article{6e077bbf-cb03-4cc3-b418-43a4ed959ca8, abstract = {{<p>Sphingosine-1-phosphate receptors (S1PRs) are promising therapeutic targets in cardiovascular disease, including ischemic stroke. However, important spatiotemporal information for alterations of S1PR expression is lacking. Here, we investigated the role of S1PR3 in ischemic stroke in rodent models and patient samples. We show that S1PR3 is acutely upregulated in perilesional reactive astrocytes after stroke, and that stroke volume and behavioral deficits are improved in mice lacking S1PR3. Further, we find that administration of an S1PR3 antagonist at 4-h post-stroke, but not at later timepoints, improves stroke outcome. Lastly, we observed higher plasma S1PR3 concentrations in experimental stroke and in patients with ischemic stroke. Together, our results establish S1PR3 as a potential drug target and biomarker in ischemic stroke.</p>}}, author = {{Matuskova, Hana and Porschen, Lisa T. and Matthes, Frank and Lindgren, Arne G. and Petzold, Gabor C. and Meissner, Anja}}, issn = {{2589-0042}}, keywords = {{Biological sciences; Molecular neuroscience; Natural sciences; Neuroscience; Pathophysiology; Physiology}}, language = {{eng}}, month = {{06}}, number = {{6}}, publisher = {{Elsevier}}, series = {{iScience}}, title = {{Spatiotemporal sphingosine-1-phosphate receptor 3 expression within the cerebral vasculature after ischemic stroke}}, url = {{http://dx.doi.org/10.1016/j.isci.2024.110031}}, doi = {{10.1016/j.isci.2024.110031}}, volume = {{27}}, year = {{2024}}, }