CORE B - This program project will investigate the effects of thoracic level spinal cord transection on lower urinary tract dysfunction using various animal models based on C57BL/10 mice (Projects 1, 2 and 3) and Sprague Dawley rats (Project 4). These models include spinal cord transected, pudendal nerve cut and ureter diverted adult mice or rats, neonatal rats and matched controls. The different projects will also use models and controls where the bladder, dorsal root ganglia or striated external urethral sphincter is injected with pseudorabies virus (PRV) linked with the genetically encoded Ca2+-indicator, GCaMP4, or GFP or RFP fluorescent indicators. PRV only transfects nerves and, depending upon the viral strain, is transported by the afferent or efferent nerves to dorsal root ganglia or spinal motoneurons in only a retrograde direction, or both retrograde and anteriograde directions. Within the spinal cord, PRV crosses synapses and is transported transneuronally in a retrograde manner to interneurons located at upstream sites on reflex pathways Animal Core B will secure and maintain the animals for the different projects. Animal orders, surgeries, postoperative care and record keeping will be carried out by the fulltime Assistant Core Director. The optimal animal numbers for each set of experiments have been determined and will continue to be adjusted with the assistance of the program's experienced statistician and his assistant. Thus, the animal core will offer the advantages of reproducibility, ease of data comparison across projects and time- and cost-effectiveness. These advantages will be further enhanced by the different projects using multiple tissues from the same animals. Animal Core B will closely interact with Imaging Core A and the project directors to effectively schedule animal preparation and usage.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK093424-02
Application #
8723178
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
DUNS #
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Kullmann, F Aura; Clayton, Dennis R; Ruiz, Wily G et al. (2017) Urothelial proliferation and regeneration after spinal cord injury. Am J Physiol Renal Physiol 313:F85-F102
Shimizu, Nobutaka; Doyal, Mark F; Goins, William F et al. (2017) Morphological changes in different populations of bladder afferent neurons detected by herpes simplex virus (HSV) vectors with cell-type-specific promoters in mice with spinal cord injury. Neuroscience 364:190-201
Miyazato, Minoru; Kadekawa, Katsumi; Kitta, Takeya et al. (2017) New Frontiers of Basic Science Research in Neurogenic Lower Urinary Tract Dysfunction. Urol Clin North Am 44:491-505
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Wada, Naoki; Shimizu, Takahiro; Takai, Shun et al. (2017) Combinational effects of muscarinic receptor inhibition and ?3-adrenoceptor stimulation on neurogenic bladder dysfunction in rats with spinal cord injury. Neurourol Urodyn 36:1039-1045
Ito, Hiroki; Pickering, Anthony E; Igawa, Yasuhiko et al. (2017) Muro-Neuro-Urodynamics; a Review of the Functional Assessment of Mouse Lower Urinary Tract Function. Front Physiol 8:49
Wada, Naoki; Shimizu, Takahiro; Takai, Shun et al. (2017) Post-injury bladder management strategy influences lower urinary tract dysfunction in the mouse model of spinal cord injury. Neurourol Urodyn 36:1301-1305

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