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 7 days. 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 6 h post-
stroke. In aged mice, DV administration was only protective when started 3 h 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.