AB296. SPR-23 Aberrant bladder reflexes can drive hind limb locomotor activity following complete suprasacral spinal cord injury

Objective: Many rats with chronic suprasacral spinal cord injury (SCI) demonstrate hind limb locomotor activity (HLLA) in response to external crede or high pressure contractions during cystometry. We propose that this aberrant, pressure-driven bladder reflex pathway may be harnessed to facilitate walking in SCI patients. As a first step in exploring this possibility, we examined the relationship between intravesical pressure (IVP) and HLLA in chronic suprasacral SCI rats.

Methods: Female rats (4 weeks post-SCI at T9-10, n=16) were anesthetized with isoflurane and fitted with transvesical catheters and right quadriceps EMG electrodes to monitor bladder and hind limb locomotor activities, respectively. The animals were mounted in Ballman restraint cages to which they had been previously acclimated. The catheter was connected to a pressure transducer, an infusion pump, and a saline-filled reservoir mounted on a metered vertical pole (pressure clamp). After 30 min of recovery from anesthesia, the bladder was filled at 0.1 mL/min with saline to verify bladder-to-bladder reflex activity for 30 min. IVP was then increased in an interrupted stepwise fashion from 0–120 cmH₂O at 10 cmH₂O increments. Each step consisted of five minutes: 3 minutes at the new pressure followed by 2 minutes at 0 cmH₂O. IVP and the number of HLLA events (as defined by rhythmic EMG discharges of 3–10 cycles/event) were recorded for each pressure step. This process was repeated for two more trials for each rat to assess the durability of the reflex. Data were analyzed using ANOVA with repeated measures both within and across pressure escalation trials. P<0.05 was considered significant.

Results: ANOVA revealed that locomotor events increased with increasing IVP and decreased with the number of escalation trials (P<0.0001 for both effects). The increase in the number of locomotor events with increasing IVP appeared to plateau at ~50–60 cmH₂O (P<0.05 for all). The average of the maximal number of locomotor events for each animal decreased steadily from ~3.0, 2.5 and 1.75 over the three trials.

Conclusions: There is a positive relationship between IVP and HLLA that suggests the emergence of an aberrant bladder-to-hind limb locomotor reflex pathway following SCI. It may be possible to harness this reflex pathway independently of the state of the bladder to facilitate walking in SCI patients.

Funding Source(s): VA RRD SPiRE RX-001749-01

Keywords: Locomotor; bladder; spinal cord injury (SCI); cystometry; neural plasticity