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Effects of activity dependent plasticity on recovery of bladder and sexual function after human spinal cord injury

Award Number: R01HD080205
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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DESCRIPTION (provided by applicant): Spinal cord injury (SCI) results in impairments of locomotor, sensory and autonomic functions, severely affecting overall health and quality of life. Recent discoveries related to activity-dependent plasticity in humans have led to a widely implemented rehabilitation intervention, Locomotor Training, which includes stepping using body weight support on a treadmill with manual facilitation. Evidence suggests that this particular type of task specific training optimizes the lumbosacral spinal circuitry. We have intriguing evidence from four SCI individuals who are unable to stand or walk showing improved bladder and sexual function after undergoing Locomotor Training. These changes in urogenital function may be due to activity-dependent plasticity of lumbosacral circuitry that mediates micturition and erectile functions. Proper bladder management post-SCI is necessary to decrease the risk of upper urinary tract disease, a major source of morbidity. The life-long urologic care is required for SCI individuals, yet most efforts treat symptoms but do not improve intrinsic function. In addition, paraplegics rank sexual function as the function post-injury that should be given the highest priority in order to enhance quality of life. This proposal focuses on the mechanisms involved in the reorganization of spinal cord circuits for bladder and sexual function in response to activity-dependent plasticity induced by step training after SCI, with and without epidural stimulation. Stand training and/or arm crank exercise serve as controls. Of potential mechanistic importance is that neurotrophins have been implicated in modulating bladder function. It is therefore hypothesized that weight bearing task specific training for locomotion post-SCI induces plasticity of neural networks that mediate not just walking but bladder and sexual function as well and may do so for bladder function by reducing specific neurotrophins that are elevated post-SCI. Our unique approach will utilize the expertise of each investigator to 1) To determine whether the effect of weight-bearing task-specific training for locomotion on voiding frequency and urodynamic parameters is due to an interaction between locomotor and urinary bladder circuitry after traumatic incomplete upper motor neuron SCI in humans (versus standing or general exercise); 2) To assess the effect of LT on urine (biomarkers) and bladder (biopsy tissue) NGF and BDNF levels after severe incomplete SCI; 3) To determine the effect of weight-bearing task-specific training for locomotion on erectile function and sexual satisfaction after traumatic incomplete upper motor neuron SCI in humans; and 4) To assess the effect of epidural stimulation in combination with LT on voiding frequency, urodynamic parameters, erectile function, and bladder/urine NGF and BDNF levels after complete and motor complete/sensory incomplete upper motor neuron SCI in humans. Our innovative multi-disciplinary study may lead to the translation of a combination approach of weight bearing step training, epidural stimulation, and neurotrophic factor manipulation to promote functional recovery for multiple systems following SCI.


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: 2023 ( Subtotal = $383,425 )
2023	2023	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Child Health and Human Development Extramural Research	000	9	7/13/2023	NON-COMPETING CONTINUATION	$383,425
														Subtotal = $383,425

Issue Date FY: 2022 ( Subtotal = $383,411 )
2022	2022	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Child Health and Human Development Extramural Research	003	8	7/11/2022	NON-COMPETING CONTINUATION	$383,425
2022	2018	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Child Health and Human Development Extramural Research	000	5	11/2/2021	NON-COMPETING CONTINUATION	$0
2022	2018	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Child Health and Human Development Extramural Research	002	5	6/29/2022	NON-COMPETING CONTINUATION	-$14
2022	2017	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Child Health and Human Development Extramural Research	001	4	6/29/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $383,411

Issue Date FY: 2021 ( Subtotal = $382,302 )
2021	2021	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Child Health and Human Development Extramural Research	000	7	7/19/2021	NON-COMPETING CONTINUATION	$382,302
														Subtotal = $382,302

Issue Date FY: 2020 ( Subtotal = $381,600 )
2020	2020	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Child Health and Human Development Extramural Research	002	6	8/4/2020	COMPETING CONTINUATION	$381,600
2020	2018	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Child Health and Human Development Extramural Research	001	5	7/28/2020	NON-COMPETING CONTINUATION	$0
2020	2018	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Child Health and Human Development Extramural Research	000	5	6/22/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $381,600

Issue Date FY: 2018 ( Subtotal = $311,250 )
2018	2018	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Child Health and Human Development Extramural Research	000	5	6/25/2018	NON-COMPETING CONTINUATION	$311,250
														Subtotal = $311,250

Issue Date FY: 2017 ( Subtotal = $311,250 )
2017	2017	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Child Health and Human Development Extramural Research	000	4	7/28/2017	NON-COMPETING CONTINUATION	$311,250
														Subtotal = $311,250

Issue Date FY: 2016 ( Subtotal = $308,137 )
2016	2016	UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION	SERVICE COMPLEX	LOUISVILLE	KY	40292	JEFFERSON	USA	Child Health and Human Development Extramural Research	000	3	6/27/2016	NON-COMPETING CONTINUATION	$308,137
														Subtotal = $308,137

Issue Date FY: 2015 ( Subtotal = $303,468 )
2015	2015	UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION	SERVICE COMPLEX	LOUISVILLE	KY	40292	JEFFERSON	USA	Child Health and Human Development Extramural Research	000	2	6/17/2015	NON-COMPETING CONTINUATION	$303,468
														Subtotal = $303,468

Issue Date FY: 2014 ( Subtotal = $311,250 )
2014	2014	UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION	SERVICE COMPLEX	LOUISVILLE	KY	40292	JEFFERSON	USA	Child Health and Human Development Extramural Research	000	1	9/22/2014	NEW	$311,250
														Subtotal = $311,250

Grand Total All Awards = $3,076,093

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Effects of activity dependent plasticity on recovery of bladder and sexual function after human spinal cord injury

Award Number: R01HD080205

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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