Deficits in ejaculation, urination, and defecation are among of the most devastating outcomes of spinal cord injury (SCI), severely affecting quality of life. The neural mechanisms are poorly understood, making restoration of function following traumatic SCI a difficult task. In humans, SCI occurs predominantly in young males and compromises sexual function, leaving most patients infertile. Moreover, bladder dysfunction is common due to the loss of synergy between the bladder and its outlet for voiding urine. In many patients, conscious control of defecation is also lost resulting in fecal incontinence and chronic constipation. Since normal ejaculation, micturition, and defecation require sequential contraction of perineal muscles that depend upon an intact segmental reflex arc and brainstem integration, we have developed and characterized an in vivo brainstem-spinal cord electrophysiological animal model to study the neurological causes of ejaculatory and eliminative dysfunctions following severe mid-thoracic SCI. 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 genitalia/pelvic organs and the medullary reticular formation. Studies in our current grant (NS40919) address important questions regarding the neural control/coordination of smooth and striated muscles sub-serving sexual, bladder and bowel functions in male rats using specific chronic lesions restricted to the dorsal 3/5 of the T8 cord. Results from our current data have raised new questions regarding injury-induced plasticity in these neural circuitries. The overall aim for this renewal grant is to use our model to investigate these injury-induced changes in order to allow us to more specifically ascertain the spinal cord regions and specific neural circuitry which should be targeted for therapeutic interventions designed to improve the control/coordination of sexual, bladder and bowel functions following chronic SCI. The knowledge gained from these studies will help direct future experiments that will be geared toward the development of therapeutic interventions that will promote functional recovery following SCI. Parallel electrophysiological, neuroanatomical and behavioral studies are once again proposed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS040919-05A2
Application #
6969957
Study Section
Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
Program Officer
Kleitman, Naomi
Project Start
2000-09-28
Project End
2010-06-30
Budget Start
2005-08-01
Budget End
2006-06-30
Support Year
5
Fiscal Year
2005
Total Cost
$272,245
Indirect Cost
Name
University of Louisville
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
057588857
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