? ? Options for enhancing patient motor recovery following stroke are extremely limited, with current standard of care for long-term treatment comprised of referral to physical therapy. Although stroke is the third leading cause of death in the United States, the majority of the 700,000 individuals afflicted each year will survive the event. Of those survivors, 50% will experience some degree of one-sided paralysis, the leading cause of disability and loss of independence among stroke patients {Association, 2003 #50}. In addition to quality of life implications, substantial economic impact arises directly from patient care and rehabilitation costs as well as loss of patient workforce productivity, and indirectly from the displacement of labor to care for the patient. The goal of the proposed project is to evaluate a novel approach to enhancing motor recovery following stroke by increasing cortical excitability and, consequently, plasticity through chronic electrical stimulation of the deep cerebellar structures in a rodent model of chronic, ischemic stroke. The central hypothesis of this proposal is that artificial activation of the net excitatory dentatothalamocortical (DTC) pathway will result in increased excitability of motor regions of cerebral cortex, facilitating neuronal plasticity and recovery of motor function. To this end, microelectrodes will be implanted in the lateral cerebellar nucleus for the purpose of delivering chronic electrical stimulation in an established rodent model of stroke.
The first aim will be to determine the parameters of electrical stimulation of the DTC pathway in the rodent model that optimize cortical motor excitability, as indexed using motor evoked potentials. These results will be used to refine the parameters used in specific aim two, a controlled study involving chronic electrical stimulation of the DTC pathway in an established rodent model of ischemic stroke in order to evaluate the effect on motor recovery.
The third aim of this application deals with the distribution of therapeutic benefit by examining whether treatment-related improvement is greater for the distal or proximal forelimb, information that will be of some benefit in patient selection. The treatment applied in this model is analogous to the therapeutic application of deep brain stimulation, which already has been demonstrated to be safe and effective in the treatment of Parkinson's disease and essential tremor. Thus, promising results from a study such as the one proposed ultimately could lead directly to trials in human patients with stroke as the hardware and techniques are already well established. ? ? ?
| Park, Hyun-Joo; Furmaga, Havan; Cooperrider, Jessica et al. (2015) Modulation of Cortical Motor Evoked Potential After Stroke During Electrical Stimulation of the Lateral Cerebellar Nucleus. Brain Stimul 8:1043-8 |
| Machado, Andre G; Cooperrider, Jessica; Furmaga, Havan T et al. (2013) Chronic 30-Hz deep cerebellar stimulation coupled with training enhances post-ischemia motor recovery and peri-infarct synaptophysin expression in rodents. Neurosurgery 73:344-53; discussion 353 |
| Baker, Kenneth B; Schuster, Daniel; Cooperrider, Jessica et al. (2010) Deep brain stimulation of the lateral cerebellar nucleus produces frequency-specific alterations in motor evoked potentials in the rat in vivo. Exp Neurol 226:259-64 |
| Machado, Andre G; Baker, Kenneth B; Schuster, Daniel et al. (2009) Chronic electrical stimulation of the contralesional lateral cerebellar nucleus enhances recovery of motor function after cerebral ischemia in rats. Brain Res 1280:107-16 |
