Post-stroke augmentation of rehabilitation-mediated functional recovery with growth factor adminstration

Abstract

Behavioural rehabilitation is the only treatment option for chronic stroke deficits. Unfortunately, even lengthy rehabilitation often provides incomplete recovery. This study used an animal model of stroke that incorporates key features of sensorimotor impairment commonly observed in stroke patients. A novel combination of growth factor administration and rehabilitation therapy was employed to facilitate functional recovery in this model. -- Sprague-Dawley rats received a stroke via injection of endothelin-1 at two sites in the sensorimotor cortex. This was followed by either a 2-week infusion of epidermal growth factor (EGF) and erythropoietin (EPO) or artificial cerebrospinal fluid (aCSF). Two weeks post-ischemia, animals began either a 6-week enriched rehabilitation program or standard housing treatment: (1) EGF/EPO + rehab; (2) aCSF + rehab; (3) EGF/EPO + no rehab; and (4) aCSF + no rehab. Functional assessments were performed pre- and post-ischemia and after 14, 28, and 42 days of rehabilitation thereafter (approximately every 3 weeks) using the Montoya staircase reaching task, beam traversing and cylinder test of forelimb asymmetry. -- The combination of EGF/EPO + rehab led to a significant acceleration in recovery on the Montoya staircase reaching task after only 2 weeks of therapy compared to rehabilitation-alone. Although the combination of EGF/EPO + rehab resulted in accelerated recovery, animals exposed to rehabilitation-alone recovered to a similar extent after 6 weeks of therapy. This effect was observed in both the staircase and beam traversing tasks where animals that received rehabilitation recovered to a significantly greater extent than standard-housed animals. -- Combining behavioural rehabilitation with growth factors that promote endogenous stem cell mobilization may accelerate recovery beyond that of rehabilitation alone. This has the potential to reduce the length of rehabilitation necessary to recover from stroke deficits.