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Acute and Chronic Repercussions of Spinal Cord Stimulation following Spinal Cord Injury

Award Number: R01NS142427
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/21/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2031

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Acute and Chronic Repercussions of Spinal Cord Stimulation following Spinal Cord Injury - Project Summary: Blood pressure instability after spinal cord injury (SCI) impairs quality of life and can be dangerous, causing loss of consciousness, stroke, and even death. This blood pressure instability is rooted in interruption of descending autonomic regulatory signals through the injured spinal cord. Our recent work quantifies the breadth of these impairments after SCI, noting severe dysfunction to both activate and inhibit sympathetic activity, with decreased compensatory baroreflex sensitivity, to a battery of laboratory-based autonomic tests. To address blood pressure instability, several case studies have shown that acute spinal cord stimulation increases blood pressure when sympathetic activation is needed. Unfortunately, the limited scope of these past experiments leaves the mechanism and broader repercussions unknown. Our pilot studies employing expanded autonomic tests suggest that both acute transcutaneous and epidural spinal cord stimulation cause static sympathetic activation to increase blood pressure, but do not improve autonomic regulation through the cord as postulated. This can be beneficial in tasks where sympathetic activation is needed but disadvantageous when sympathetic inhibition is needed, commonly pushing individuals towards potentially dangerous autonomic dysreflexia. This later point is key, as autonomic dysreflexia is associated with immunosuppression and accelerated cardiovascular disease. While these acute stimulation effects are potentially worrisome, spinal cord stimulation will likely be a chronic intervention. Chronically supplying sympathetic tone may facilitate intact regulatory mechanisms like the baroreflex to stabilize blood pressure as well as mitigate autonomic drivers of immunosuppression and cardiovascular disease. This study seeks to apply our lab-based autonomic testing battery to robustly quantify if acute or chronic spinal cord stimulation improves autonomic regulation and the associated immunologic and cardiovascular repercussions. To achieve this, we propose the following two aims. Aim 1: Quantify changes in autonomic regulation from acute and chronic spinal cord stimulation and define mechanisms of increased blood pressure. Aim 2: Assess systemic repercussions of acute and chronic spinal cord stimulation after SCI. In 60 total individuals with SCI, baseline autonomic regulation will be quantified with thorough, lab-based autonomic testing. Biomarkers of acute and chronic immune function (T-cell exhaustion markers and antigen recall response), as well as cardiovascular function (vascular dysfunction biomarkers and ambulatory blood pressure monitoring) will capture broader, clinically relevant systemic repercussions. Individuals will have all testing repeated with the addition of acute and 10 days (chronic) of spinal cord stimulation. Changes from baseline in autonomic regulatory, immune, and cardiovascular function will be quantified. In 20 controls, baseline autonomic regulation and biomarker assays will bolster our established normative control database (to n=51) to identify if changes in key endpoints represent normalization. Quantified changes will help to either safely translate spinal cord stimulation to clinic or give the field pause to reconsider how to optimize this potentially promising approach.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $622,784 )
2026	2026	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/20/2026	NEW	$622,784
														Subtotal = $622,784

Grand Total All Awards = $622,784

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Acute and Chronic Repercussions of Spinal Cord Stimulation following Spinal Cord Injury

Award Number: R01NS142427

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/21/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2031

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