title: Lack of collagen XV is protective after ischemic stroke in mice.
abstract: Collagens are key structural components of basement membranes, providing a scaffold for other components or adhering cells. Collagens and collagen-derived active fragments contribute to biological activities such as cell growth, differentiation and migration. Here, we report that collagen XV knock-out (ColXV KO) mice are resistant to experimental ischemic stroke. Interestingly, the infarcts of ColXV KO mice were as small as those of wild-type (WT) mice thrombolysed with recombinant tissue plasminogen activator (rtPA), the actual treatment for ischemic stroke. Importantly, there were no differences in the architecture of cerebrovascular anatomy between WT and ColXV KO mice. We found a twofold increase of the most potent pro-angiogenic factor, type A vascular growth endothelial factor (VEGF-A) in the ipsilateral cortex of rtPA-treated ischemic WT mice compared with untreated ischemic and sham-operated counterparts. A similar increase of VEGF-A was also found in both rtPA and untreated ischemic ColXV KO mice compared with sham ColXV KO mice. Finally, we evidenced that the levels of ColXV were increased in the plasma of WT mice treated with rtPA compared with untreated ischemic counterparts. Altogether, this study indicates that the lack ColXV is protective after stroke and that the degradation of endothelial ColXV may contribute to the beneficial effect of rtPA after ischemic stroke. The neuroprotection observed in ColXV KO mice may be attributed to the increased VEGF-A production following stroke in the ischemic territory.
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: Hiramani
authors.initials: H
authors.lastname: Dhungana
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: Mikko T
authors.initials: MT
authors.lastname: Huuskonen
authors.affiliation: Oulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Pihlajaniemi
authors.affiliation: Oulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.|Centre for Cancer Biomarkers CCBIO, Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Ritva
authors.initials: R
authors.lastname: Heljasvaara
authors.affiliation: Normandie Univ, UNICAEN, INSERM U919, Serine Proteases and Pathophysiology of the neurovascular Unit, Cyceron, Caen, France.|Department of Clinical Research, Caen University Hospital, Avenue de la côte de Nacre, Caen, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: Katja M
authors.initials: KM
authors.lastname: Kanninen
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Malm
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Koistinaho
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: Sighild
authors.initials: S
authors.lastname: Lemarchant
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D000066829:Neuroprotection / Q000235:genetics; D020521:Stroke / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D023822:Tissue Engineering; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000235:genetics; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C553732:collagen XV, mouse; D003094:Collagen; D010959:Tissue Plasminogen Activator