Abstract
Task-specific rehabilitative training is commonly used for chronic stroke patients. Axonal remodeling is believed to be one mechanism underlying rehabilitation-induced functional recovery, and significant roles of the corticospinal pathway have previously been demonstrated. Brainstem-spinal pathways, as well as the corticospinal tract, have been suggested to contribute to skilled motor function and functional recovery after brain injury. However, whether axonal remodeling in the brainstem-spinal pathways is a critical component for rehabilitation-induced functional recovery is not known. In this study, rats were subjected to photothrombotic stroke in the caudal forelimb area of the primary motor cortex and received rehabilitative training with a skilled forelimb reaching task for 4 weeks. After completion of the rehabilitative training, the retrograde tracer Fast blue was injected into the contralesional lower cervical spinal cord. Fast blue-positive cells were counted in 32 brain areas located in the cerebral cortex, hypothalamus, midbrain, pons, and medulla oblongata. Rehabilitative training improved motor performance in the skilled forelimb reaching task but not in the cylinder test, ladder walk test, or staircase test, indicating that rehabilitative skilled forelimb training induced task-specific recovery. In the histological analysis, rehabilitative training significantly increased the number of Fast blue-positive neurons in the ipsilesional rostral forelimb area and secondary sensory cortex. However, rehabilitative training did not alter the number of Fast blue-positive neurons in any areas of the brainstem. These results indicate that rehabilitative skilled forelimb training enhances axonal remodeling selectively in the corticospinal pathway, which suggests a critical role of cortical plasticity, rather than brainstem plasticity, in task-specific recovery after subtotal motor cortex destruction.
Highlights
Stroke is a major cause of disability worldwide and rehabilitation is commonly used to treat chronic stroke patients
We chose to conduct our experiments in Fisher 344 rats, because neural network remodeling and motor map reorganization induced by rehabilitative training have been well investigated in this strain [13,14,15]
We investigated the effects of rehabilitative skilled forelimb training (Rehab) on functional recovery and axonal remodeling in the descending spinal pathways after photothrombosis (PT) (Fig 1A)
Summary
Stroke is a major cause of disability worldwide and rehabilitation is commonly used to treat chronic stroke patients. Disability of the upper extremities is a common impairment experienced by a large majority of stroke survivors. Many forms of rehabilitative therapy, especially taskspecific training, have long been used to improve upper limb dexterity following stroke. In the recent guideline for stroke rehabilitation, task-specific training is still considered to be a more beneficial and reliable form of therapy than newly developed rehabilitative methods such as transcranial magnetic stimulation, transcranial direct current stimulation, robotic therapy, or virtual reality [1]. The majority of recently developed or developing therapies are expected to be combined with task-specific training, implying a central role of task-specific training in future stroke therapies [2]. Despite its popularity in clinical settings, the precise mechanism by which task-specific training promotes functional recovery remains to be elucidated
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