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Electrical stimulation treatment to enhance connectivity between brainstem and spinal defecation centers for improved volitional control of the bowel after spinal cord injury in the rat

Award Number: R21NS144942
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: 09/05/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Electrical stimulation treatment to enhance connectivity between brainstem and spinal defecation centers for improved volitional control of the bowel after spinal cord injury in the rat - Project Summary/Abstract Persistent disturbances of bowel function occur in a large majority of people with spinal cord injury (SCI). Neurogenic bowel is a major physical and psychological challenge that reduces quality of life for people with SCI. Current treatments are focused on bowel management, but offer little in the way of improvement or recovery. People living with SCI list bladder and bowel dysfunction as among the most debilitating consequences of SCI. Nonetheless, these impairments are poorly studied and there are limited efforts to develop new treatments compared to the research on improving motor function. We will address these shortcomings in an exploratory project to begin development of novel therapies to improve bowel function after SCI. Although most current research focuses on treatments directed at the enteric nervous system or autonomic outflow, we hope to strengthen connections between the brainstem and lumbosacral spinal defecation centers that are damaged by injury. We have previously shown that electrical stimulation of the spinal cord triggered on movement-related activity in cortical neurons or ipsilesional muscles strengthens connections between the brain and spinal cord, and improves forelimb motor function after cervical SCI in rats. We have strong evidence that this protocol recruits Hebbian plasticity in specific, movement-related neural pathways. We will deploy an analogous intervention targeting damaged connections between brainstem and spinal defecation centers that regulate parasympathetic control of the distal colon and somatic control of the external anal sphincter. However, it is unclear what physiological signal(s) can be used to trigger spinal stimulation to effectively induce activity-dependent plasticity in these pathways after SCI. We will investigate the properties of neurons in Barrington’s nucleus and a putative lateral cell group that provide important inputs to the parasympathetic cell column and motoneurons of the external anal sphincter in the lumbosacral cord, respectively. In anesthetized and behaving animals, we will correlate neural activity in these areas with bowel function in uninjured rats and in rats after contusion injury of the mid-thoracic spinal cord. These experiments will identify the location and timing of signals in the brainstem related to distal colon distension. In a second set of experiments, we will use these signals in awake rats to trigger stimulation of the spinal parasympathetic defecation center and external anal sphincter motoneurons for many weeks to induce plasticity in these pathways. Colonic and whole gut motility and fecal output will be measured to determine if the intervention improves bowel function.


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 = $233,250 )
2026	2026	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/4/2026	NEW	$233,250
														Subtotal = $233,250

Grand Total All Awards = $233,250

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Electrical stimulation treatment to enhance connectivity between brainstem and spinal defecation centers for improved volitional control of the bowel after spinal cord injury in the rat

Award Number: R21NS144942

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: 09/05/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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