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School of Public Health
Department: Biomedical Sciences
Identifies the harmful plasticity that occurs after spinal cord injury leads to urinary dysfunction, and the development of methods for counteracting or reversing this harmful plasticity to improve urinary function.
Campus phone: (518) 486-4911
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Disordered urinary tract function is among the most common and most disabling, but least studied consequences of spinal cord injury (SCI). Interruption by SCI of the normal control by the brain of the spinal cord typically results in impairment or even loss of the ability to store and/or void urine. The result is often chronic infection and impaired general health. These urinary tract deficits occur as the direct result of loss of control signals from the brain and also as a result of changes in nerve function (called plasticity) in the spinal cord below the level of the injury. In some cases, this plasticity is beneficial; in other cases, it can be harmful and can exacerbate urinary dysfunction.
The primary interest of professor Carp’s laboratory is the identification of the harmful plasticity that occurs after SCI that leads to urinary dysfunction, and the development of methods for counteracting or reversing this harmful plasticity to improve urinary function. An example of this harmful plasticity is what happens to the nerve cells that control the external urethral sphincter (EUS) muscle. This muscle serves as a valve that allows or blocks the expulsion of urine from the bladder. When these EUS nerve cells (called motoneurons) lose their normal inputs after SCI, they have the ability to increase their own intrinsic level of excitability, apparently in an attempt to recover their normal function. If their excitability increases too much, they do not turn off to allow urine to flow when the bladder is full. This often results in urinary retention and chronic infections.
There are two projects currently ongoing in this laboratory. The first project is to determine if EUS motoneuron over-excitability can be reduced pharmacologically to allow more normal control of urination after SCI using drugs that interact with two brain chemicals—serotonin and norepinephrine—that are normally released onto these EUS motoneurons by neural pathways that descend from the brain. These pathways are often interrupted by SCI. We believe that the loss of these pathways causes EUS motoneurons to increase their excitability (like automatic gain control on a radio when the incoming signal becomes weak), and that this increase produces urinary retention. A class of drugs called inverse agonists have the ability to prevent this increase in excitability, even when the normal brain pathways are not working.
The second project involves enhancing the pathways from the brain that are compromised after incomplete SCI that control the EUS motoneurons in the spinal cord. The goal of this project is to use operant conditioning techniques developed at the Wadsworth Center to induce beneficial plasticity to improve the efficacy of the brain’s control over the EUS motoneurons after SCI. This approach could also be useful for treatment of the urinary dysfunction that frequently occurs after traumatic brain injury or neurodegenerative disease.