The lower urinary tract has two functions: urine storage and elimination. During storage, the bladder is relaxed while the urethra is closed by tonic contraction of the urethral sphincter. When the bladder is full, voiding occurs as a result of bladder contraction and simultaneous relaxation of the urethral sphincter. This coordination between bladder and urethra sphincter is normally controlled by a spinobulbospinal micturition reflex. However, after spinal cord injury (SCI) above the lumbar level the brain control is lost and spinal reflex mechanisms emerge, which produce both detrusor overactivity - bladder contracts frequently even at relatively small volumes, and detrusor sphincter dyssynergia - urethral sphincter and bladder contract simultaneously. These lower urinary tract dysfunctions have a tremendous impact on the quality of life in people with SCI. Current treatments have either limited success or troublesome side effects. The long-term goals of this project are to reveal the neural mechanisms contributing to neurogenic detrusor overactivity and to characterize several lower urinary tract reflexes that could be used to normalize voiding function in people with SCI. In order to determine the spinal mechanisms underlying the recovery of bladder-to-bladder and somato-to-bladder reflexes after SCI, we will employ spinal functional magnetic resonance imaging, electrophysiological, and immunocytochemical techniques to examine the spinal organization and properties of these reflexes in normal, acute and chronic SCI cats and the mechanism underlying the spinal interactions between somatic and parasympathetic afferent inputs. Previous studies in other labs and our preliminary studies have demonstrated that both inhibitory and excitatory somato-to-bladder reflexes can be induced in normal and SCI animals or humans depending on stimulation location and frequency. The neural circuitry and neurotransmitters involved in these inhibitory or excitatory somato-to-bladder reflexes will be studied with electrophysiological and pharmacological techniques. Understanding the neuroplasticity underlying functional changes of lower urinary tract reflexes after SCI, and revealing the neural pathways and neurotransmitters involved in these reflexes will not only improve our knowledge about micturition control, but will also stimulate the development of more effective treatments for people with SCI and improve the quality of life. ^
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