Spatiotemporal sphingosine-1-phosphate receptor 3 expression within the cerebral vasculature after ischemic stroke
Hana Matuskova,
Lisa T. Porschen,
Frank Matthes,
Arne G. Lindgren,
Gabor C. Petzold,
Anja Meissner
Affiliations
Hana Matuskova
Department of Experimental Medical Sciences, Lund University, 221 84 Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, 221 84 Lund, Sweden; Division of Vascular Neurology, University Hospital Bonn, 53127 Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
Lisa T. Porschen
Department of Experimental Medical Sciences, Lund University, 221 84 Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, 221 84 Lund, Sweden; Department of Physiology, Institute of Theoretical Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany
Frank Matthes
Department of Experimental Medical Sciences, Lund University, 221 84 Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, 221 84 Lund, Sweden; Department of Physiology, Institute of Theoretical Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany
Arne G. Lindgren
Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden; Department of Neurology, Rehabilitation Medicine, Memory Disorders and Geriatrics, Skåne University Hospital, Lund, Sweden
Gabor C. Petzold
Division of Vascular Neurology, University Hospital Bonn, 53127 Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
Anja Meissner
Department of Experimental Medical Sciences, Lund University, 221 84 Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, 221 84 Lund, Sweden; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany; Department of Physiology, Institute of Theoretical Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany; Corresponding author
Summary: 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.
