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Harnessing spinal electrical stimulation to modulate autonomic function after spinal cord injury

Project description

Rehabilitation neuroprosthesis for spinal cord injury

Severe spinal cord injury (SCI) can damage sympathetic nerves responsible for cardiovascular control and can lead to hypertension or orthostatic hypotension. These conditions not only have limited treatment options but are also associated with an increased risk for cardiovascular disease. To prevent these clinical conditions, the EU-funded symESTIM project is developing an electrical neuroprosthesis capable of restoring autonomic function after SCI. Researchers are employing state-of-the-art technologies to dissect the neuronal circuits that get damaged after SCI in experimental animal models. This will allow them to map the neuronal connections in the spinal cord that need to be electrically stimulated in a neurorehabilitation approach after SCI.

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.

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 191 149,44
Address
BATIMENT CE 3316 STATION 1
1015 LAUSANNE
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Vaud
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 191 149,44
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