http://www.ncbi.nlm.nih.gov/m/pubmed/19038917/?i=2&from=/21886364/related
Papadopoulos CM, et al. Stroke. 2009.
Abstract
BACKGROUND AND PURPOSE:
There is considerable debate regarding the efficacy of
amphetamine to facilitate motor recovery after stroke or experimental
brain injury. Different drug dosing and timing schedules and differing
physical rehabilitation strategies may contribute to outcome
variability. The present study was designed to ascertain (1) whether
short-term amphetamine could induce long-term functional motor recovery
in rats after an ischemic lesion modeling stroke in humans; (2) how
different levels of physical rehabilitation interact with amphetamine to
enhance forelimb-related functional outcome; and (3) whether motor
improvement was associated with axonal sprouting from intact
corticoefferent pathways originating in the contralesional forelimb
motor cortex.
METHODS:
After permanent middle cerebral artery occlusion, rats
received vehicle or amphetamine during the first postoperative week (2
mg/kg, subcutaneously on Postoperative Days 2, 5, and 8). In both
treatment groups, separate cohorts of rats were exposed to different
levels of "physical rehabilitation" represented by a control
environment, enriched environment, or enriched environment with
additional sessions of focused activity. Skilled forelimb performance
was assessed using the forelimb reaching task and ladder rung walk test.
Anterograde tracing with biotinylated dextran amine was used to assess
new fiber outgrowth to denervated motor areas.
RESULTS:
All treatment groups showed significant motor improvement as
compared with control-housed, vehicle-treated animals. However, animals
housed in an enriched environment that received amphetamine paired with
focused activity sessions performed significantly better than any other
treatment group and was the only group to achieve complete motor
recovery (ie, reached preoperative performance) by 8 weeks. This
recovery was associated with axonal sprouting into deafferentated
subcortical areas from contralesional projection neurons.
CONCLUSIONS:
This study suggests that, after stroke, short-term pairing
of amphetamine with sufficiently focused activity is an effective means
of inducing long-term improvement in forelimb motor function. The
anatomic data suggests that corticoefferent plasticity in the form of
axonal sprouting contributes to the maintenance of motor recovery.
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