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Recovery of bladder function after SCI with opsin-based sensorimotor modulation

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Spinal cord injury (SCI) at nearly any segmental level results in loss of supraspinally mediated, volitional control over bladder function. During an acute period of spinal shock after injury, urinary retention due to an areflexic bladder precedes remodeling of synaptic connections in the spinal cord that give rise to involuntary, spinally mediated micturition. However, changes in synergistic afferent and efferent activity lead to detrusor sphincter dyssynergia, thus urinary retention persists. Consequently, urogenital and renal health and overall quality of life are negatively impacted. Innovative bioengineering technologies that allow for modulation of sensory and motor activity with light offer high potential for recovery of organ control in injured individuals. Further, using sensorimotor modulation to maintain coordinated bladder and external urethral sphincter (EUS) contraction and relaxation in the acute stage following SCI when remodeling is occurring may facilitate long-term recovery of coordination, and may help prevent the development of secondary sequelae including detrusor-sphincter dyssynergia. Channelrhodopsin-2 (ChR2) and archaerhodopsin (Arch) are membrane proteins that excite or inhibit, respectively, cells in response to specific wavelengths of light. ChR2 and Arch can be introduced into eukaryotic cells by genetic targeting using cell-type specific promoters or by viral gene delivery, which is translatable to humans. We propose to combine ChR2- and Arch-mediated excitation and inhibition of bladder and EUS activity in vivo in a preclinical, mouse spinal cord contusion model. We hypothesize that early intervention following SCI by sensorimotor modulation with light-controlled opsins will effectively control urine voiding and facilitate adaptive neuronal plasticity to establish an efficient spinally mediated voiding reflex. We will combine in vivo behavioral techniques (cystometry, electromyography) and molecular strategies (detection of cFos and MAP kinase phosphorylation) to determine the effective opsin-based neuromodulation parameters for eliciting a voiding reflex and the spinal cord pathways engaged at acute and subacute time points after SCI. Then, we will compare and contrast the effects of early versus delayed intervention consisting of daily sensorimotor modulation with dual wavelengths via ChR2 and Arch on coordination of bladder and EUS contraction/relaxation, voiding behavior, and spinal synaptic remodeling. (CHN: SCIRTS chn:wdg)
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    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC


  • RCDC

    Spinal Cord Injury

  • RCDC


  • RCDC

    Urologic Diseases



  • Health Research Areas


  • Broad Research Areas

    Basic Science