NDLI: Perlecan Domain V Is Neuroprotective and Affords Functional Improvement in a Photothrombotic Stroke Model in Young and Aged Mice

Content Provider	Springer Nature Link
Author	Bix, Gregory J. Gowing, Emma K. Clarkson, Andrew N.
Copyright Year	2013
Abstract	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.
Starting Page	515
Ending Page	523
Page Count	9
File Format	PDF
ISSN	18684483
Journal	Translational Stroke Research
Volume Number	4
Issue Number	5
e-ISSN	1868601X
Language	English
Publisher	Springer US
Publisher Date	2013-06-07
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cerebral infarct Extracellular matrix Behavioral recovery Neurosciences Neurology Cardiology Neurosurgery Vascular Surgery
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Neuroscience Neurology (clinical)

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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