title: A microchannel neuroprosthesis for bladder control after spinal cord injury in rat.
abstract: A severe complication of spinal cord injury is loss of bladder function (neurogenic bladder), which is characterized by loss of bladder sensation and voluntary control of micturition (urination), and spontaneous hyperreflexive voiding against a closed sphincter (detrusor-sphincter dyssynergia). A sacral anterior root stimulator at low frequency can drive volitional bladder voiding, but surgical rhizotomy of the lumbosacral dorsal roots is needed to prevent spontaneous voiding and dyssynergia. However, rhizotomy is irreversible and eliminates sexual function, and the stimulator gives no information on bladder fullness. We designed a closed-loop neuroprosthetic interface that measures bladder fullness and prevents spontaneous voiding episodes without the need for dorsal rhizotomy in a rat model. To obtain bladder sensory information, we implanted teased dorsal roots (rootlets) within the rat vertebral column into microchannel electrodes, which provided signal amplification and noise suppression. As long as they were attached to the spinal cord, these rootlets survived for up to 3 months and contained axons and blood vessels. Electrophysiological recordings showed that half of the rootlets propagated action potentials, with firing frequency correlated to bladder fullness. When the bladder became full enough to initiate spontaneous voiding, high-frequency/amplitude sensory activity was detected. Voiding was abolished using a high-frequency depolarizing block to the ventral roots. A ventral root stimulator initiated bladder emptying at low frequency and prevented unwanted contraction at high frequency. These data suggest that sensory information from the dorsal root together with a ventral root stimulator could form the basis for a closed-loop bladder neuroprosthetic.
authors.affiliation: Cambridge Centre for Brain Repair, University of Cambridge, Cambridge CB2 0PY, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Chew
authors.forename: Lan
authors.initials: L
authors.lastname: Zhu
authors.forename: Evangelos
authors.initials: E
authors.lastname: Delivopoulos
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Minev
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Musick
authors.forename: Charles A
authors.initials: CA
authors.lastname: Mosse
authors.forename: Michael
authors.initials: M
authors.lastname: Craggs
authors.forename: Nicholas
authors.initials: N
authors.lastname: Donaldson
authors.forename: Stéphanie P
authors.initials: SP
authors.lastname: Lacour
authors.forename: Stephen B
authors.initials: SB
authors.lastname: McMahon
authors.forename: James W
authors.initials: JW
authors.lastname: Fawcett
mesh_terms: D000200:Action Potentials; D000818:Animals; D001369:Axons / Q000473:pathology; D004558:Electric Stimulation; D005260:Female; D020007:Implants, Experimental; D008839:Microelectrodes; D009186:Myelin Sheath / Q000378:metabolism; D009407:Nerve Block; D058117:Neural Prostheses; D009929:Organ Size; D011474:Prosthesis Design; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013126:Spinal Nerve Roots / Q000098:blood supply / Q000503:physiopathology / Q000601:surgery; D001743:Urinary Bladder / Q000503:physiopathology*; D014554:Urination