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The Journal of Neuroscience, August 23, 2006, 26(34):8672-8679; doi:10.1523/JNEUROSCI.1259-06.2006

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Development/Plasticity/Repair
Functional Reinnervation of the Rat Lower Urinary Tract after Cauda Equina Injury and Repair

Thao X. Hoang,¹ Victor Pikov,² and Leif A. Havton¹

¹Department of Neurology and Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095, and ²Huntington Medical Research Institutes, Pasadena, California 91105

Correspondence should be addressed to Dr. Leif A. Havton, Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769. Email: lhavton{at}mednet.ucla.edu

Conus medullaris and/or cauda equina forms of spinal cord injury commonly result in a permanent loss of bladder function. Here, we developed a cauda equina injury and repair rodent model to investigate whether surgical implantation of avulsed lumbosacral ventral roots into the spinal cord can promote functional recovery of the lower urinary tract. Adult female rats underwent sham surgery (n = 6), bilateral L5–S2 ventral root avulsion (VRA) injury (n = 5), or bilateral L5–S2 VRA followed by an acute implantation of the avulsed L6 and S1 ventral roots into the conus medullaris (n = 6). At 12 weeks after operation, the avulsed group demonstrated urinary retention, absence of bladder contractions and external urethral sphincter (EUS) electromyographic (EMG) activation during urodynamic recordings, increased bladder size, and retrograde death of autonomic and motoneurons in the spinal cord. In contrast, the implanted group showed reduced urinary retention, return of reflexive bladder voiding contractions coincident with EUS EMG activation, anatomical reinnervation of the EUS demonstrated by retrograde neuronal labeling, normalization of bladder size, and a significant neuroprotection of both autonomic and motoneurons. In addition, a positive correlation between motoneuronal survival and voiding efficiency was observed in the implanted group. Our results show that implantation of avulsed lumbosacral ventral roots into the spinal cord promotes reinnervation of the urinary tract and return of functional micturition reflexes, suggesting that this surgical repair strategy may also be of clinical interest after conus medullaris and cauda equina injuries.

Key words: bladder; autonomic; regeneration; spinal cord; ventral root avulsion; urodynamic

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Received March 23, 2006; revised June 19, 2006; accepted July 17, 2006.

Correspondence should be addressed to Dr. Leif A. Havton, Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769. Email: lhavton{at}mednet.ucla.edu

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