Hubscher Laboratory of Translational Neuroscience
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About
Dr. Hubscher’s research involves a multidisciplinary approach geared toward understanding the circuitries and neural mechanisms underlying urinary, bowel and sexual functions. Research since the mid-1990’s has focused on the impact of spinal cord injury on pelvic organ functions with the goal of developing more effective therapeutic approaches for translation directly to the clinic. Various combinations of neurophysiological, behavioral, immunohistochemical, molecular and neuroanatomical techniques are being used in Dr. Hubscher’s pre-clinical laboratory. Translational studies since 2014, through collaborations at The University of Louisville’s Kentucky Spinal Cord Injury Research Center at Frazier Rehab Institute, have focused on activity-based recovery training, including the impact of locomotor training and spinal cord epidural stimulation (each alone or in combination). We work collaboratively across multiple disciplines that include experts in urology, gastroenterology, neurosurgery, physical medicine & rehabilitation, and bioengineering to employ research driven “Discovery-to-Recovery” approach.
Key Research Areas
- Spinal Cord Injury
- Bladder
- Bowel
- Ejaculation
- Polyuria
- Autonomic Dysreflexia
- Epidural Stimulation
- Locomotor Training
Current Projects
- Effects of activity dependent plasticity on recovery of bladder and sexual function after spinal cord injury (National Institutes of Health): The goals in the current phase of this ongoing multi-disciplinary pilot clinical trial incorporating critical cross viscero-visceral intersystem interactions are a) to investigate in a controlled laboratory setting and then with mobile at-home monitoring the extent, severity and frequency of occurrence of autonomic dysreflexia with respect to daily bladder and bowel function, and b) to regulate cardiovascular function therapeutically as part of bladder and bowel management using spinal cord epidural stimulation in order to normalize blood pressure.
- Functional mapping with lumbosacral epidural stimulation for restoration of bladder function after spinal cord injury (National Institutes of Health): The goals of this spinal cord epidural stimulation (scES) pilot clinical trial are a) to determine the optimal stimulation parameters for bladder storage and emptying in SCI research participants already implanted with the scES Medtronic device (16 electrode array from L1-S1); b) to quantify the long-term effects of daily bladder training using optimal scES parameters; c) to assess secondary benefits (bladder medication usage, susceptibility to urinary tract infections, indirect cardiovascular, bowel and sexual function benefits) of long-term bladder training; d) to enable dynamic human in-the-loop sensor feedback learning algorithm-controlled neuromodulation of micturition pathways and cardiovascular function in the home environment and improve the transition from bladder storage to voiding in the home-setting by flexibly adjusting the preset parameters; and e) to address with a small animal model the impact of scES location and stimulation parameters on bladder and bowel function in intact, T9-transected and T9-contused male and female rats.
- Effects of activity dependent plasticity on bowel function after spinal cord injury (Department of Defense): The goal of the current ongoing experiments is to a) collect baseline outcome data on colonic motility and rectal/anal sphincter dynamics at multiple time-points after incomplete SCI and b) examine the impact of activity based training on bowel function with various time manipulations to address a key question regarding the maintenance of benefits from the locomotor training rehabilitation strategy.
- Spinal cord epidural stimulation for male reproductive organ function after spinal cord injury (Kentucky Spinal Cord and Head Injury Research Trust): The goals of this pre-clinical study are to a) identify the optimal spinal cord epidural stimulation (scES) location and parameters for emission and expulsion of seminal fluid; b) determine the impact of spinal cord injury on sperm quality and testicular histopathology; and c) assess the effect of locomotor training on sensitivity to scES, sperm quality, testicular health, and the incidence of retrograde ejaculation.
- Targeting urinary tract dysfunctions after spinal cord injury with epidural stimulation (National Institutes of Health): The goals of this spinal cord epidural stimulation (scES) pre-clinical study are to build upon our initial clinical trial findings to recommend improvements for the existing technology (re electrode design) and ways to further strengthen functional outcomes (with a combinatory approach). There are limitations in human studies to explore mechanisms. The rat is a widely used model for spinal cord injury (SCI) and bladder function due to the many similar injury responses and lower urinary tract (LUT) functional features to humans. We have specifically designed these rat studies with targeted questions that focus upon various critical and basic mechanisms to better tailor electrode parameters to enhance outcome, inform the development of a closed loop system for LUT function, and better facilitate daily management, health, reduce health-care costs, and improve quality of life.
Recent Publications
Bladder Responses to Thoracolumbar Epidural Stimulation in Female Urethane-Anesthetized Rats with Graded Contusion Spinal Cord Injuries.
Wilkins NL, Medina-Aguiñaga D, Hoey RF, Fell J, Harkema SJ, Hubscher CH. J Neurotrauma. 2024 Sep 26. doi: 10.1089/neu.2024.0209. PMID: 39264865
Impact of Activity-Based Training on Bowel Function in a Rat Model of Spinal Cord Injury.
Fell JD, Medina-Aguiñaga D, Burke DA, Hubscher CH. J Neurotrauma. 2024 May;41(9-10):1181-1195. doi: 10.1089/neu.2023.0486. Epub 2024 Jan 31. PMID: 38117145
Mid-lumbar (L3) epidural stimulation effects on bladder and external urethral sphincter in non-injured and chronically transected urethane-anesthetized rats.
Medina-Aguiñaga D, Hoey RF, Wilkins NL, Ugiliweneza B, Fell J, Harkema SJ, Hubscher CH. Sci Rep. 2023 Jul 28;13(1):12258. doi: 10.1038/s41598-023-39388-9.PMID: 37507456
Predictive values of spinal cord diffusion magnetic resonance imaging to characterize outcomes after contusion injury.
Ahmed RU, Medina-Aguinaga D, Adams S, Knibbe CA, Morgan M, Gibson D, Kim JW, Sharma M, Chopra M, Davison S, Sherwood LC, Negahdar MJ, Bert R, Ugiliweneza B, Hubscher C, Budde MD, Xu J, Boakye M.Ann Clin Transl Neurol. 2023 Sep;10(9):1647-1661. doi: 10.1002/acn3.51855. Epub 2023 Jul 27. PMID: 37501362
Targeted selection of stimulation parameters for restoration of motor and autonomic function in individuals with spinal cord injury.
Angeli, C., Rejc, E., Boakye, M., Herrity, A., Mesbah, S., Hubscher, C., Forrest, G., Harkema, S. (2023) Neuromodulation. 2024 Jun;27(4):645-660. doi: 10.1016/j.neurom.2023.03.014. Epub 2023 May 4. PMID: 37140522
Targeting bladder function with network-specific epidural stimulation after chronic spinal cord injury.
Herrity AN, Aslan SC, Mesbah S, Siu R, Kalvakuri K, Ugiliweneza B, Mohamed A, Hubscher CH, Harkema SJ. Sci Rep. 2022 Jul 1;12(1):11179. doi: 10.1038/s41598-022-15315-2.PMID: 35778466
Impact of activity-based recovery training and desmopressin on spinal cord injury-induced polyuria in Wistar rats.
Hubscher CH, Gumbel JH, Armstrong JE, Montgomery LR. J Spinal Cord Med. 2023 Nov;46(6):910-916. doi: 10.1080/10790268.2022.2069538. Epub 2022 May 23. PMID: 35604340
Effect of T3 Spinal Contusion Injury on Upper Urinary Tract Function.
Gumbel JH, Hubscher CH.Neurotrauma Rep. 2022 Apr 26;3(1):190-198. doi: 10.1089/neur.2022.0014. eCollection 2022.PMID: 35558732
Thoracolumbar epidural stimulation effects on bladder and bowel function in uninjured and chronic transected anesthetized rats.
Hoey RF, Medina-Aguiñaga D, Khalifa F, Ugiliweneza B, Wang D, Zdunowski S, Fell J, Naglah A, El-Baz AS, Herrity AN, Harkema SJ, Hubscher CH.Sci Rep. 2022 Feb 8;12(1):2137. doi: 10.1038/s41598-022-06011-2.
Team
- James Armstrong, Research Coordinator V, jearms01@louisville.edu
- Daniel Medina Aguinaga, MD/PhD, Senior Research Scientist, d0medi01@louisville.edu
- Cuibo Yang, Research Assistant III; c0yang01@louisville.edu
- Terri Manning, Clinical Research Program Manager, trmann01@louisville.edu
- Siqi Wang, PhD, Senior Research Scientist (Clinical Program), s0wang22@louisville.edu
- Kyle Beasley, Doctoral Candidate, kmbeas02@louisville.edu
- Betsy Perez De Corcho Vazquez, Doctoral Candidate, betsy.perezdecorcho@louisville.edu