The neural mechanisms involved in the control/coordination of urogenital functions is poorly understood, making restoration of function following traumatic spinal cord injury a difficult task. In humans, spinal cord injury occurs predominantly in young males, compromises sexual function, and leaves most patients infertile because of an inability to ejaculate. Moreover, bladder voiding dysfunction is common due to bladder-sphincter dyssynergia. Incoordination of perineal motoneuron circuits, resulting from spinal cord injury-induced changes in non-locomotor segmental reflex circuits involved in male reproductive function and micturition, likely contributes to these complications. Since normal ejaculation and micturition require both an intact segmental reflex arc and brainstem integration, we have, in recent years, developed and characterized an in vivo brainstem-spinal cord electrophysiological animal model to study the neurological causes of sexual dysfunction following severe midthoracic spinal cord injury. Our previous studies with this model have shown that chronic bilateral lesions of the dorsal 3/5 of T8 spinal cord is correlated with (i) impaired bladder/sexual reflexes, (ii) changes in lumbosacral neural circuits mediating perineal muscle function and (iii) loss of ascending and descending connections between the distal urogenital tract and the medullary reticular formation (ii/iii - as determined in terminal electrophysiological experiments). The overall aim of the proposed research is to use this spino-bulbo-spinal model to address important questions regarding the neural control/coordination of smooth and striated muscles subserving sexual and bladder functions in male rats following chronic spinal cord injury. A unique benefit of our model lies in our ability to focus on the integration of information from multiple pelvic viscera. The knowledge gained from these basic scientific experiments will more specifically ascertain the spinal cord regions and the specific neural circuitry which should be targeted for therapeutic interventions designed to improve the control/coordination of sexual, bladder and bowel functions following chronic spinal cord injury. Parallel electrophysiological, behavioral and neuroanatomical studies are proposed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS040919-04
Application #
6529661
Study Section
Special Emphasis Panel (ZNS1-SRB-L (01))
Program Officer
Kleitman, Naomi
Project Start
2000-09-28
Project End
2005-07-31
Budget Start
2002-09-01
Budget End
2005-07-31
Support Year
4
Fiscal Year
2002
Total Cost
$180,625
Indirect Cost
Name
University of Louisville
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
City
Louisville
State
KY
Country
United States
Zip Code
40292
Ward, Patricia J; Hubscher, Charles H (2012) Persistent polyuria in a rat spinal contusion model. J Neurotrauma 29:2490-8
Johnson, Richard D; Chadha, Harpreet K; Dugan, Victoria P et al. (2011) Bilateral bulbospinal projections to pudendal motoneuron circuitry after chronic spinal cord hemisection injury as revealed by transsynaptic tracing with pseudorabies virus. J Neurotrauma 28:595-605
Hubscher, Charles H; Kaddumi, Ezidin G; Johnson, Richard D (2008) Segmental neuropathic pain does not develop in male rats with complete spinal transections. J Neurotrauma 25:1241-5
Cothron, Kyle J; Massey, James M; Onifer, Stephen M et al. (2008) Identification of penile inputs to the rat gracile nucleus. Am J Physiol Regul Integr Comp Physiol 294:R1015-23
Onifer, Stephen M; Nunn, Christine D; Decker, Julie A et al. (2007) Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury. Exp Neurol 207:238-47
Kaddumi, Ezidin G; Hubscher, Charles H (2007) Urinary bladder irritation alters efficacy of vagal stimulation on rostral medullary neurons in chronic T8 spinalized rats. J Neurotrauma 24:1219-28
Kaddumi, Ezidin G; Hubscher, Charles H (2007) Changes in rat brainstem responsiveness to somatovisceral inputs following acute bladder irritation. Exp Neurol 203:349-57
Kaddumi, Ezidin G; Hubscher, Charles H (2006) Convergence of multiple pelvic organ inputs in the rat rostral medulla. J Physiol 572:393-405
Hubscher, Charles H; Johnson, Richard D (2004) Effects of chronic dorsal column lesions on pelvic viscerosomatic convergent medullary reticular formation neurons. J Neurophysiol 92:3596-600
Hubscher, Charles H; Kaddumi, Ezidin G; Johnson, Richard D (2004) Brain stem convergence of pelvic viscerosomatic inputs via spinal and vagal afferents. Neuroreport 15:1299-302