Summary
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.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/896791 |
| Start date: | 01-03-2020 |
| End date: | 28-02-2022 |
| Total budget - Public funding: | 191 149,44 Euro - 191 149,00 Euro |
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Original description
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.Status
CLOSEDCall topic
MSCA-IF-2019Update Date
28-04-2024
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