Abstract
Objective. Bladder dysfunction is a significant and largely unaddressed problem for people living with spinal cord injury (SCI). Intermittent catheterization does not provide volitional control of micturition and has numerous side effects. Targeted electrical microstimulation of the spinal cord has been previously explored for restoring such volitional control in the animal model of experimental SCI. Here, we continue the development of the intraspinal microstimulation array technology to evaluate its ability to provide more focused and reliable bladder control in the feline animal model. Approach. For the first time, a mechanically robust intraspinal multisite silicon array was built using novel microfabrication processes to provide custom-designed tip geometry and 3D electrode distribution. Long-term implantation was performed in eight spinally intact animals for a period up to 6 months, targeting the dorsal gray commissure area in the S2 sacral cord that is known to be involved in the coordination between the bladder detrusor and the external urethral sphincter. Main results. About one third of the electrode sites in the that area produced micturition-related responses. The effectiveness of stimulation was further evaluated in one of eight animals after spinal cord transection (SCT). We observed increased bladder responsiveness to stimulation starting at 1 month post-transection, possibly due to supraspinal disinhibition of the spinal circuitry and/or hypertrophy and hyperexcitability of the spinal bladder afferents. Significance. 3D intraspinal microstimulation arrays can be chronically implanted and provide a beneficial effect on the bladder voiding in the intact spinal cord and after SCT. However, further studies are required to assess longer-term reliability and safety of the developed intraspinal microstimulation array prior to eventual human translation.
Highlights
Approximately 300,000 individuals are currently living with spinal cord injury (SCI) in the United States with annual incidence of 54 cases per one million, or about 17,700 new cases annually (NSCISC 2018)
The approach based on electrical microstimulation inside the spinal cord may provide such volitional control
After measuring the EUS tone and bladder pressure response to microstimulation, the bladder was filled with saline warmed to 37°C to a pressure of about 30 mmHg, and the catheter was removed from the urethra for testing the effectiveness of the most effective electrode sites in inducing micturition
Summary
300,000 individuals are currently living with spinal cord injury (SCI) in the United States with annual incidence of 54 cases per one million, or about 17,700 new cases annually (NSCISC 2018). The array and some surgical and testing tools (insertion tool with hex ranches, cable for perigenital stimulation, ball electrode for the recording of evoked potentials, and a connector cable for pressure transducer and a bladder catheter for urodynamics) were sterilized with ethylene oxide for 24 hours using a room-temperature system (Anprolene AN74i, Andersen Products, Haw River, NC).
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