naa a22 4500 510776132 CHVBK 20180411083230.0 cr unu---uuuuu 180411e20131001xx s 000 0 eng 10.1007/s12975-013-0266-1 doi (NATIONALLICENCE)springer-10.1007/s12975-013-0266-1 Perlecan Domain V Is Neuroprotective and Affords Functional Improvement in a Photothrombotic Stroke Model in Young and Aged Mice [Elektronische Daten] [Gregory Bix, Emma Gowing, Andrew Clarkson] With the failure of so many pre-clinical stroke studies to translate into the clinic, there is a need to find new therapeutics to minimize the extent of cellular damage and aid in functional recovery. Domain V (DV), the c-terminal protein fragment of the vascular basement membrane component, perlecan, was recently shown to afford significant protection in multiple transient middle cerebral artery occlusion stroke models. We sought here to determine whether DV might have similar therapeutic properties in a focal photothrombosis stroke model in both young and aged mice. Young (3-month old) and aged (24-month old) mice underwent photothrombotic stroke to the motor cortex and were then treated with DV or phosphate buffered saline vehicle at different initial time points up to 7days. Stroke volume was analyzed histologically using cresyl violet and functional recovery assessed behaviorally on both the grid-walking and cylinder tasks. In young mice, DV administration resulted in a significant decrease in infarct volume when treatment started 3 or 6h post-stroke. In aged mice, DV administration was only protective when started 3h post-stroke. In addition to a decrease in the area of infarction, DV treatment was effective in significantly decreasing the number of foot-faults on the grid-walking task and improving use of the stroke-affected limb in the cylinder task in both young and aged. Previously, we have shown that DV can alter the expression profile of various astroglial markers. Consistent with our previous finding, treatment groups that showed therapeutic potential in both young and aged mice also showed an elevation in glial fibrillary acidic protein (GFAP) expression in peri-infarct regions. We conclude that DV is neuroprotective and affords significant improvements in functional recovery in both young and aged mice after focal ischemia. These data also highlight a therapeutic time-window shift that is narrower in aged compared with young mice and is associated with an elevation in GFAP expression and heightened astrogliosis. Springer Science+Business Media New York, 2013 Cerebral infarct nationallicence Extracellular matrix nationallicence Behavioral recovery nationallicence Bix Gregory Anatomy and Neurobiology, University of Kentucky College of Medicine, Sanders Brown Center for Aging, 40536, Lexington, KY, USA aut Gowing Emma Anatomy, University of Otago, P.O. Box 913, 9054, Dunedin, New Zealand aut Clarkson Andrew Anatomy, University of Otago, P.O. Box 913, 9054, Dunedin, New Zealand aut Translational Stroke Research Springer US; http://www.springer-ny.com 4/5(2013-10-01), 515-523 1868-4483 4:5<515 2013 4 12975 https://doi.org/10.1007/s12975-013-0266-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12975-013-0266-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bix Gregory Anatomy and Neurobiology, University of Kentucky College of Medicine, Sanders Brown Center for Aging, 40536, Lexington, KY, USA aut NATIONALLICENCE 700 1- Gowing Emma Anatomy, University of Otago, P.O. Box 913, 9054, Dunedin, New Zealand aut NATIONALLICENCE 700 1- Clarkson Andrew Anatomy, University of Otago, P.O. Box 913, 9054, Dunedin, New Zealand aut NATIONALLICENCE 773 0- Translational Stroke Research Springer US; http://www.springer-ny.com 4/5(2013-10-01), 515-523 1868-4483 4:5<515 2013 4 12975 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer