Original Article

A novel approach to induction and rehabilitation of deficits in forelimb function in a rat model of ischemic stroke

Authors: Jessica Mary Livingston-Thomas, Andrew Wilson Hume, Tracy Ann Doucette, Richard Andrew Tasker
DOI: 10.1038/aps.2012.106

Abstract

Jessica Mary Livingston-Thomas1, Andrew Wilson Hume1, Tracy Ann Doucette2, Richard Andrew Tasker1, *

1Departments of Biomedical Sciences and 2Biology, University of Prince Edward Island, Charlottetown, PE, Canada C1A4P3

Aim: Constraint-induced movement therapy (CIMT), which forces use of the impaired arm following unilateral stroke, promotes functional recovery in the clinic but animal models of CIMT have yielded mixed results. The aim of this study is to develop a refined endothelin-1 (ET-1) model of focal ischemic injury in rats that resulted in reproducible, well-defined lesions and reliable upper extremity impairments, and to determine if an appetitively motivated form of rehabilitation (voluntary forced use movement therapy; FUMT) would accelerate post-ischemic motor recovery.

Methods: Male Sprague Dawley rats (3 months old) were given multiple intracerebral microinjections of ET-1 into the sensorimotor cortex and dorsolateral striatum. Sham-operated rats received the same surgical procedure up to but not including the drill holes on the skull. Functional deficits were assessed using two tests of forelimb placing, a forelimb postural reflex test, a forelimb asymmetry test, and a horizontal ladder test. In a separate experiment ET-1 stroke rats were subjected to daily rehabilitation with FUMT or with a control therapy beginning on post-surgery d 5. Performance and post-mortem analysis of lesion volume and regional BDNF expression were measured.

Results: Following microinjections of ET-1 animals exhibited significant deficits in contralateral forelimb function on a variety of tests compared with the sham group. These deficits persisted for up to 20 d with no mortality and were associated with consistent lesion volumes. FUMT therapy resulted in a modest but significantly accelerated recovery in the forelimb function as compared with the control therapy, but did not affect lesion size or BDNF expression in the ipsilesional hemisphere.

Conclusion: We conclude that refined ET-1 microinjection protocols and forcing use of the impaired forelimb in an appetitively motivated paradigm may prove useful in developing strategies to study post-ischemic rehabilitation and neuroplasticity.


Keywords:stroke; brain ischemia; endothelin-1; rehabilitation therapy; voluntary forced use movement therapy (FUMT); BDNF; neuroplasticity

Jessica Mary LIVINGSTON-THOMAS is supported by a post-graduate scholarship from the PEI Prosperity Strategy. Research funding was provided by Atlantic Innovation Fund grant 193639 to Richard Andrew TASKER.
* To whom correspondence should be addressed.
E-mail tasker@upei.ca
Received 2012-03-29 Accepted 2012-07-04
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