Epidermal growth factor and erythropoietin infusion accelerate functional recovery in combination with rehabilitation.
OBJECTIVE
Rehabilitation is the only treatment option for chronic stroke deficits, but unfortunately, it often provides incomplete recovery. In this study, a novel combination of growth factor administration and rehabilitation therapy was used to facilitate functional recovery in a rat model of cortical stroke.


METHODS
Ischemia was induced via injection of endothelin-1 into the sensorimotor cortex. This was followed by either a 2-week infusion of epidermal growth factor and erythropoietin or artificial cerebrospinal fluid into the ipsilateral lateral ventricle. Two weeks after ischemia, animals began an 8-week enriched rehabilitation program. Functional recovery was assessed after ischemia using the Montoya staircase-reaching task, beam-traversing, and cylinder test of forelimb asymmetry.


RESULTS
The combination of growth factor infusion and rehabilitation led to a significant acceleration in recovery in the staircase task. When compared with controls, animals receiving the combination treatment attained significant recovery of function at 4 weeks after stroke, whereas those receiving rehabilitation alone did not recover until 10 weeks. Significant recovery was also observed on the beam-traversing and cylinder tasks.


CONCLUSIONS
Combining behavioral rehabilitation with growth factor infusion accelerates motor recovery. These data suggest a promising new avenue of combination therapies that may have the potential to reduce the rehabilitation time necessary to recover from sensorimotor deficits arising from stroke.
From the Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada (M.S.J., D.C.); Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Ottawa, Ontario, Canada (C.M., D.C.); Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada (M.S.J., D.C.); and Departments of Medicine (D.C.) and Surgery (A.H., C.M.), University of Toronto, Toronto, Ontario, Canada.
Matthew S
MS
Jeffers
From the Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada (M.S.J., D.C.); Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Ottawa, Ontario, Canada (C.M., D.C.); Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada (M.S.J., D.C.); and Departments of Medicine (D.C.) and Surgery (A.H., C.M.), University of Toronto, Toronto, Ontario, Canada.
Amy
A
Hoyles
From the Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada (M.S.J., D.C.); Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Ottawa, Ontario, Canada (C.M., D.C.); Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada (M.S.J., D.C.); and Departments of Medicine (D.C.) and Surgery (A.H., C.M.), University of Toronto, Toronto, Ontario, Canada.
Cindi
C
Morshead
From the Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada (M.S.J., D.C.); Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Ottawa, Ontario, Canada (C.M., D.C.); Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada (M.S.J., D.C.); and Departments of Medicine (D.C.) and Surgery (A.H., C.M.), University of Toronto, Toronto, Ontario, Canada. dcorbett@uottawa.ca.
Dale
D
Corbett
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000633:toxicity; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004921:Erythropoietin / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000139:chemically induced / Q000503:physiopathology*; D000071939:Stroke Rehabilitation
D019332:Endothelin-1; D004921:Erythropoietin; D004815:Epidermal Growth Factor
endothelin-1; epidermal growth factor; erythropoietin; rehabilitation; stroke