Deficiency of vasodilator-stimulated phosphoprotein (VASP) increases blood-brain-barrier damage and edema formation after ischemic stroke in mice.
Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP) is an important regulator of actin dynam...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-12-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2997079?pdf=render |
| _version_ | 1819212861542498304 |
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| author | Peter Kraft Peter Michael Benz Madeleine Austinat Marc Elmar Brede Kai Schuh Ulrich Walter Guido Stoll Christoph Kleinschnitz |
| author_facet | Peter Kraft Peter Michael Benz Madeleine Austinat Marc Elmar Brede Kai Schuh Ulrich Walter Guido Stoll Christoph Kleinschnitz |
| author_sort | Peter Kraft |
| collection | DOAJ |
| description | Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP) is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification.Focal cerebral ischemia was induced in Vasp(-/-) mice and wild-type (WT) littermates by transient middle cerebral artery occlusion (tMCAO). Evan's Blue tracer was applied to visualize the extent of blood-brain-barrier (BBB) damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p<0.05) and edema volumes (1.7 mm(3)±0.5 mm(3) versus 0.8 mm(3)±0.4 mm(3); p<0.0001) were significantly enhanced in Vasp(-/-) mice compared to controls on day 1 after tMCAO. This was accompanied by a significant increase in infarct size (56.1 mm(3)±17.3 mm(3) versus 39.3 mm(3)±10.7 mm(3), respectively; p<0.01) and a non significant trend (p>0.05) towards worse neurological outcomes.Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage. |
| first_indexed | 2024-12-23T06:49:42Z |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T06:49:42Z |
| publishDate | 2010-12-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-b050a6588c3a4108937572fabf497d342022-12-21T17:56:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-12-01512e1510610.1371/journal.pone.0015106Deficiency of vasodilator-stimulated phosphoprotein (VASP) increases blood-brain-barrier damage and edema formation after ischemic stroke in mice.Peter KraftPeter Michael BenzMadeleine AustinatMarc Elmar BredeKai SchuhUlrich WalterGuido StollChristoph KleinschnitzStroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP) is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification.Focal cerebral ischemia was induced in Vasp(-/-) mice and wild-type (WT) littermates by transient middle cerebral artery occlusion (tMCAO). Evan's Blue tracer was applied to visualize the extent of blood-brain-barrier (BBB) damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p<0.05) and edema volumes (1.7 mm(3)±0.5 mm(3) versus 0.8 mm(3)±0.4 mm(3); p<0.0001) were significantly enhanced in Vasp(-/-) mice compared to controls on day 1 after tMCAO. This was accompanied by a significant increase in infarct size (56.1 mm(3)±17.3 mm(3) versus 39.3 mm(3)±10.7 mm(3), respectively; p<0.01) and a non significant trend (p>0.05) towards worse neurological outcomes.Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage.http://europepmc.org/articles/PMC2997079?pdf=render |
| spellingShingle | Peter Kraft Peter Michael Benz Madeleine Austinat Marc Elmar Brede Kai Schuh Ulrich Walter Guido Stoll Christoph Kleinschnitz Deficiency of vasodilator-stimulated phosphoprotein (VASP) increases blood-brain-barrier damage and edema formation after ischemic stroke in mice. PLoS ONE |
| title | Deficiency of vasodilator-stimulated phosphoprotein (VASP) increases blood-brain-barrier damage and edema formation after ischemic stroke in mice. |
| title_full | Deficiency of vasodilator-stimulated phosphoprotein (VASP) increases blood-brain-barrier damage and edema formation after ischemic stroke in mice. |
| title_fullStr | Deficiency of vasodilator-stimulated phosphoprotein (VASP) increases blood-brain-barrier damage and edema formation after ischemic stroke in mice. |
| title_full_unstemmed | Deficiency of vasodilator-stimulated phosphoprotein (VASP) increases blood-brain-barrier damage and edema formation after ischemic stroke in mice. |
| title_short | Deficiency of vasodilator-stimulated phosphoprotein (VASP) increases blood-brain-barrier damage and edema formation after ischemic stroke in mice. |
| title_sort | deficiency of vasodilator stimulated phosphoprotein vasp increases blood brain barrier damage and edema formation after ischemic stroke in mice |
| url | http://europepmc.org/articles/PMC2997079?pdf=render |
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