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Principal Investigator: Patrick D Ganzer
Organization: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
Fiscal Year: 2024
Award: $477,556
Funding agency: National Institute of Neurological Disorders and Stroke
Abstract
Almost all sympathetic outflow control pathways travel through the spinal cord for affecting the peripheral tissues.
Cervical spinal cord injury impacts sympathetic outflow control, leading to several debilitating deficits (in addition
to paralysis), including an inability to redistribute blood to active tissues and muscle fatigue. There are currently
no consistently effective treatments for sympathetic outflow control dysfunction following cervical spinal cord
injury. The long-term goal of this research is to address this significant gap using vagus nerve stimulation paired
with rehabilitation to enhance sympathetic outflow control following cervical spinal cord injury. Pairing vagus
nerve stimulation with movements during rehabilitation leads to the rapid release of plasticity enhancing
neuromodulators, leading to the reorganization of motor control systems. The objective of this proposal is to
determine the specific effects of vagus nerve stimulation paired with rehabilitation on sympathetic outflow control
following cSCI, and determine the neural pathways contributing to these effects. We will also assess the optimal
delivery regime for vagus nerve stimulation (with or without rehabilitation). Our central hypothesis is that vagus
nerve stimulation precisely paired with movements during rehabilitation enhances the plasticity of spared
sympathetic outflow control circuits, leading to improved motor endurance and muscle fatigue resistance
following cSCI. We will assess this hypothesis via three specific aims: 1) determine the effects of vagus nerve
stimulation paired with rehabilitation on forelimb muscle and cardiovascular function; and measure changes in
2) cortical and 3) subcortical plasticity related to sympathetic outflow control. We will pursue these aims using
multidisciplinary assessments, leveraging electrophysiological and neuroanatomical techniques. The proposed
research is significant, as it will determine if vagus nerve stimulation paired with rehabilitation is a viable therapy
for treating sympathetic control dysfunction following cervical spinal cord injury. Furthermore, these results will
elucidate the critical relationships between forelimb function, sympathetic outflow control, vagus nerve
stimulation therapy, and neuroplasticity.
Terms: <Address><Affect><Animals><Apoplexy><Area><Aujeszky's Disease Virus><Aujeszkys Disease Virus><Baroreceptor Reflex><Baroreflex><Behavior><Blood><Blood Reticuloendothelial System><Blood flow><Body Tissues><Brain Vascular Accident><CNS plasticity><Cardiovascular><Cardiovascular Body System><Cardiovascular Organ System><Cardiovascular Physiology><Cardiovascular system><Cell Nucleus><Cerebral Stroke><Cerebrovascular Apoplexy><Cerebrovascular Stroke><Cervical Injury><Cervical spinal cord injury><Common Rat Strains><Data><Dedications><Dysfunction><Electrophysiology><Electrophysiology (science)><Event><Food and Drug Administration><Fore-Brain><Forebrain><Forelimb><Functional disorder><Goals><Health><Heart Vascular><Herpesvirus 1 (alpha), Suid><Herpesvirus Suis><Human><Hypothalamic structure><Hypothalamus><Investigation><Lateral><Maps><Measures><Medical Rehabilitation><Medulla Spinalis><Membrum superius><Mission><Modeling><Modern Man><Motor><Movement><Muscle><Muscle Fatigue><Muscle Tissue><Muscle function><Muscular Fatigue><NIH><National Institutes of Health><Nervous System Injuries><Nervous System Trauma><Nervous System damage><Neural Pathways><Neuranatomies><Neuranatomy><Neuroanatomies><Neuroanatomy><Neurological Damage><Neurological Injury><Neurological trauma><Neuromodulator><Neuronal Plasticity><Neurophysiology / Electrophysiology><Nucleus><Organ><Palsy><Paralysed><Pathway interactions><Patients><Perfusion><Peripheral><Physiology><Physiopathology><Plegia><Prosencephalon><Pseudorabies virus><Public Health><Rat><Rats Mammals><Rattus><Recovery><Rehabilitation><Rehabilitation therapy><Research><Resistance><Spinal Cord><Spinal Cord Trauma><Spinal Trauma><Spinal cord injured><Spinal cord injury><Stroke><Suid Herpesvirus 1><Swine Herpesvirus 1><Synapses><Synaptic><System><Techniques><Technology><Testing><Therapeutic><Time><Tissues><Training><Traumatic Myelopathy><Travel><USFDA><United States Food and Drug Administration><United States National Institutes of Health><Upper Extremity><Upper Limb><Upper limb movement><Work><body movement><brain attack><cardiovascular function><central nervous system plasticity><cerebral vascular accident><cerebrovascular accident><cholinergic><circulatory system><effective therapy><effective treatment><electrophysiological><exercise intolerance><experience><experiment><experimental group><experimental research><experimental study><experiments><hypothalamic><improved><mad itch virus><microstimulation><motor control><multidisciplinary><muscular><neural circuit><neural circuitry><neural control><neural plasticity><neural regulation><neurocircuitry><neuromodulation><neuromodulatory><neuroplastic><neuroplasticity><neuroregulation><neurotransmitter release><neurotrauma><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><paralysis><paralytic><pathophysiology><pathway><rehab therapy><rehabilitative><rehabilitative therapy><resistant><simulation><stroked><strokes><synapse><synaptic circuit><synaptic circuitry><translational opportunities><translational potential><vagus nerve stimulation>