http://stroke.ahajournals.org/content/early/2018/01/23/STROKEAHA.117.019202
Visual Overview
Abstract
Background and Purpose—Chronic
impairment of the arm and hand is a common consequence of stroke.
Animal and human studies indicate that brief bursts of vagus nerve
stimulation (VNS) in conjunction with rehabilitative training improve
recovery of motor function after stroke. In this study, we tested
whether VNS could promote generalization, long-lasting recovery, and
structural plasticity in motor networks.
Methods—Rats
were trained on a fully automated, quantitative task that measures
forelimb supination. On task proficiency, unilateral cortical and
subcortical ischemic lesions were administered. One week after ischemic
lesion, rats were randomly assigned to receive 6 weeks of rehabilitative
training on the supination task with or without VNS. Rats then
underwent 4 weeks of testing on a task assessing forelimb strength to
test generalization of recovery. Finally, the durability of VNS benefits
was tested on the supination task 2 months after the cessation of VNS.
After the conclusion of behavioral testing, viral tracing was performed
to assess synaptic connectivity in motor networks.
Results—VNS
enhances plasticity in corticospinal motor networks to increase
synaptic connectivity to musculature of the rehabilitated forelimb.
Adding VNS more than doubled the benefit of rehabilitative training, and
the improvements lasted months after the end of VNS. Pairing VNS with
supination training also significantly improved performance on a
similar, but untrained task that emphasized volitional forelimb
strength, suggesting generalization of forelimb recovery.
Conclusions—This
study provides the first evidence that VNS paired with rehabilitative
training after stroke (1) doubles long-lasting recovery on a complex
task involving forelimb supination, (2) doubles recovery on a simple
motor task that was not paired with VNS, and (3) enhances structural
plasticity in motor networks.
- Received August 23, 2017.
- Revision received November 28, 2017.
- Accepted December 21, 2017.
- © 2018 American Heart Association, Inc.
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