symESTIM · Harnessing spinal electrical stimulation to modulate autonomic function after spinal cord injury
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-03-01 → 2022-02-28
- EU contribution
- €191,149
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Harnessing spinal electrical stimulation to modulate autonomic function after spinal cord injury
Autonomic dysfunction (i.e., the unconscious control of many of the body’s systems) is a top health priority after spinal cord injury (SCI), and cardiovascular issues (i.e., a major autonomic function) are the #1 cause of death. Brief, but severe, decreases and increases in blood pressure are some of the most common effects of autonomic dysfunction after SCI and these issues are well-established risk factors for stroke and heart attack (both of which those with SCI suffer from at an alarming rate). The clinical options for managing swings in blood pressure are limited. Drugs are designed to either increase or decrease blood pressure, and most last hours to a full day, meaning that clinically managing blood pressure in those with SCI is extremely difficult. New technology capable of electrically stimulating the spinal cord, or “neuroprosthetics”, has become a promising therapy for recovering voluntary motor function after SCI. Our pilot data shows that this same intervention may be able to restore autonomic control of blood pressure. My fellowship work aimed to: a) utilize targeted spinal electrical stimulation to acutely improve autonomic/cardiovascular function after SCI; b) employ chronic spinal electrical stimulation to neurorehabilitate autonomic control of blood pressure after SCI; and c) understand the mechanisms underlying neuroprosthetic-mediated improvements of autonomic function after SCI. This proposal seeks to address this important knowledge gap. The overall OBJECTIVES of this fellowship were to understand the sympathetic nervous system connectome, reveal how a clinically- relevant SCI alters these circuits, and harness this knowledge to develop a neurorehabilitation paradigm grounded in the fundamental mechanisms of epidural electrical spinal cord stimulation.
Data: CORDIS, © European Union
Project objective
Severe spinal cord injury (SCI) interrupts descending sympatho-excitatory axons responsible for cardiovascular control. Devoid of supraspinal input, sympathetic circuits within the spinal cord undergo significant plastic changes. These changes lead to a debilitating clinical scenario that includes frequent bouts of hypertension (autonomic dysreflexia) and orthostatic hypotension, conditions which have extremely limited treatment options and lead to increased risk for cardiovascular disease. Here, I propose to deconstruct the sympathetic circuitry within the spinal cord in order to develop a targeted electrical neuroprosthesis that prevents the development of these clinical conditions. To dissect the sympathetic circuitry that drives sympathetic dysfunction after SCI, I will deploy judicious associations of optogenetics, chemogenetics, calcium imaging, virus-mediated tract-tracing and whole brain-spinal cord imaging in transgenic rats. For example, the catecholaminergic specificity of TH:Cre rats will enable the visualization of the residual descending sympatho-excitatory axons following severe contusion SCI, and will provide specific access to splanchnic ganglia neurons. This understanding of the sympathetic circuitry will allow me to map the hemodynamic responses following electrical spinal cord stimulation to the modulation of specific circuits and connections. This knowledge will then guide the development of a tailored neuroprosthesis targeting these circuits in order to regulate sympathetic dysfunction after SCI. Finally, I will exploit this neuroprosthesis to rehabilitate the sympathetic system after SCI, which I will demonstrate with longitudinal functional assessments and detailed anatomical evaluations. My ultimate goal is to develop targeted autonomic neurorehabilitation—a novel method to treat autonomic dysfunction after SCI that will improve the quality of life of those suffering from this condition.
Original text from CORDIS.
Participants
- ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE · LausanneCoordinatorSwitzerland
Links
Data: CORDIS, © European Union