One of the leading causes of morbidity resulting from neurological disorders such as spinal cord injury (SCI) is the loss of control over the lower urinary tract. SCI results in loss of voluntary control of bladder evacuation, bladder overactivity during storage (bladder hyper-reflexia) and the bladder and urethral sphincter contract simultaneously (bladder-sphincter dysynergia) instead of in a coordinated manner. Bladder-sphincter dysynergia prevents complete elimination of urine, generates high bladder pressure and requires daily urethral catheterization. These events can lead to urinary tract infections, incontinence and vesico-ureteral reflux with ensuing kidney damage. These problems result in a decreased quality of life, large medical costs and a substantial negative social and psychological impact on patients and their families. Electrical stimulation of sacral motor nerve roots can restore bladder voiding after SCI;however only when combined with the irreversible surgical transection of the sensory spinal nerve roots (i.e., a dorsal rhizotomy) to eliminate reflex contractions of the urethral sphincter that otherwise prevent voiding. Other effects of the rhizotomy (loss of remaining sensation, reflex sexual function and reflex defecation) limit the clinical acceptance of this procedure. The goal of the proposed project is to develop a neural prosthesis to restore bladder function that does not require a dorsal rhizotomy. We propose an innovative approach using afferent (sensory) stimulation that exploits the existing spinal circuitry to produce voiding. We have previously shown that electrical stimulation of sensory nerves can evoke bladder contractions and produce voiding. This project will demonstrate the feasibility of using sensory stimulation combined with motor stimulation to produce voiding. This approach would eliminate the need for a dorsal rhizotomy and, if successful, can be rapidly moved into clinical deployment. Complementary experiments will be conducted in animals and people with SCI to quantify the effectiveness of this approach and to translate animal model results to human feasibility studies. This approach to restoration of bladder voiding is expected to increase our understanding of afferent-mediated neurophysiology of the lower urinary tract and, more importantly, to increase the number of people who benefit from neuroprosthetic bladder control to improve their health and quality of life while reducing costs to the healthcare system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK077089-03
Application #
7643378
Study Section
Urologic and Kidney Development and Genitourinary Diseases Study Section (UKGD)
Program Officer
Kirkali, Ziya
Project Start
2007-09-01
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
3
Fiscal Year
2009
Total Cost
$248,312
Indirect Cost
Name
Case Western Reserve University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Bourbeau, Dennis J; Creasey, Graham H; Sidik, Steven et al. (2018) Genital nerve stimulation increases bladder capacity after SCI: A meta-analysis. J Spinal Cord Med 41:426-434
McCoin, Jaime L; Bhadra, Narendra; Brose, Steven W et al. (2015) Does patterned afferent stimulation of sacral dermatomes suppress urethral sphincter reflexes in individuals with spinal cord injury? Neurourol Urodyn 34:219-23
Franke, Manfred; Bhadra, Niloy; Bhadra, Narendra et al. (2014) Direct current contamination of kilohertz frequency alternating current waveforms. J Neurosci Methods 232:74-83
McCoin, Jaime L; Bhadra, Narendra; Gustafson, Kenneth J (2013) Electrical stimulation of sacral dermatomes can suppress aberrant urethral reflexes in felines with chronic spinal cord injury. Neurourol Urodyn 32:92-7
Boger, Adam; Bhadra, Narendra; Gustafson, Kenneth J (2013) Different clinical electrodes achieve similar electrical nerve conduction block. J Neural Eng 10:056016
Gustafson, Kenneth J; Grinberg, Yanina; Joseph, Sheeba et al. (2012) Human distal sciatic nerve fascicular anatomy: implications for ankle control using nerve-cuff electrodes. J Rehabil Res Dev 49:309-21
Boger, Adam S; Bhadra, Narendra; Gustafson, Kenneth J (2012) High frequency sacral root nerve block allows bladder voiding. Neurourol Urodyn 31:677-82
Sanders, P M H; Ijzerman, M J; Roach, M J et al. (2011) Patient preferences for next generation neural prostheses to restore bladder function. Spinal Cord 49:113-9
Foldes, Emily L; Ackermann, D Michael; Bhadra, Niloy et al. (2011) Design, fabrication and evaluation of a conforming circumpolar peripheral nerve cuff electrode for acute experimental use. J Neurosci Methods 196:31-7
Mariano, Timothy Y; Bhadra, Narendra; Gustafson, Kenneth J (2010) Suppression of reflex urethral responses by sacral dermatome stimulation in an acute spinalized feline model. Neurourol Urodyn 29:494-500

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