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Bladder nerve-smooth muscle function remains intact after long-term decentralization

Login to Access Video or Poster Abstract: MP42-11
Sources of Funding: NIH-NINDS NS070267

Introduction

The impact of autonomic nerve injury on smooth muscle is not well understood. We explored the integrity of the nerve-smooth muscle functional unit following sacral root decentralization._x000D_ _x000D_

Methods

Female canines were surgically decentralized by bilateral transection of all spinal roots caudal to L7, including the dorsal root of L7. Video surveillance of housing cages allowed measurement of the frequency and duration of urination postures at monthly intervals post operatively (PO) by observers blinded to the surgical interventions. Retrograde labeling of pelvic plexus neuronal cell bodies was quantitated from Fluorogold injected near the ureterovesical junction 3 weeks before euthanasia. Functional integrity of the pelvic plexus-bladder innervation was determined by electrical stimulation of the pelvic plexus immediately prior to euthanasia. Bladder caspase-3 immunostaining for cellular apoptosis was quantified to confirm integrity.

Results

Micturition postures were observed in only 2/6 animals by 2 months PO and 3/6 by 4 months PO while postures remained intact in sham animals. Nerve stimulation caused a robust increase in detrusor pressure in both control and decentralized groups. Likewise, abundant Fluorogold-labeled neuronal cell bodies were observed in ganglia in the pelvic plexus of both sham and decentralized animals. Immunohistochemical stain for caspase-3 showed no difference across groups. No co-localization of Fluorogold-positive neuronal tissue and caspase-3 was observed.

Conclusions

Behavioral changes observed PO confirms that decentralization reduces sensation of bladder fullness. The ability of 3/6 animals to sense bladder fullness at 4 months PO may be from sensory nerve sprouting or variations in the bladder sensory innervation. Fluorogold-positive pelvic plexus ganglia in decentralized animals demonstrates that the ganglia remained intact up to 6 months after decentralization despite sensory losses. Caspase-3 staining results showed no increase in apoptosis in the neuronal tissues or bladder smooth muscle in decentralized dogs, suggesting no increased apoptotic cell death. No significant difference between detrusor pressure responses across groups after nerve-evoked stimulation indicates that the nerve-smooth muscle functional unit of the bladder is intact up to 12 months after injury and therefore, nerve reinnervation strategies could be successful.

Funding

NIH-NINDS NS070267

Authors
Danielle M Salvadeo
Ekta Tiwari
Nagat Frara
Alan S. Braverman
Mary F. Barbe
Michael Ruggieri
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