Determining integrity of bladder innervation and smooth muscle function 1 year after lower spinal root transection in canines

Salvadeo, Danielle M.; Tiwari, Ekta; Frara, Nagat; Mazzei, Michael; Brown, Justin M.; Braverman, Alan S.; Barbe, Mary F.; Ruggieri, Michael R.

doi:10.1002/nau.23765

Cited by 9 publications

(24 citation statements)

References 12 publications

(14 reference statements)

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“…Future experiments in bladder decentralization animal models should transect the dorsal root of L7 in addition to all sacral roots to achieve more complete decentralization of the bladder from lower lumbar and sacral spinal cord segments, as performed recently for acute bladder decentralization studies, 10 and for 1 year decentralization studies in which bladder integrity and contractility was examined. 12 We have reported that the rerouting procedures did not disrupt sympathetic projections to the bladder from caudal mesenteric ganglia. 13 We extend those results here to report that numbers of labeled neurons projecting to the urethral sphincter and bladder from sacral STG were significantly lower (yet not absent) in sacral decentralized groups compared with sham/unoperated controls.…”

Section: Discussionmentioning

confidence: 92%

“…Yet, sacrally decentralized animals showed similar numbers of labeled neurons in L7 DRG as sham control animals. Future experiments in bladder decentralization animal models should transect the dorsal root of L7 in addition to all sacral roots to achieve more complete decentralization of the bladder from lower lumbar and sacral spinal cord segments, as performed recently for acute bladder decentralization studies, and for 1 year decentralization studies in which bladder integrity and contractility was examined …”

Section: Discussionmentioning

confidence: 99%

“…After electrophysiological testing, all animals were euthanized by a terminal dose of euthasol (pentobarbital sodium 86 mg/kg and phenytoin sodium 11 mg/kg, IV). Tissues were collected, fixed by immersion, and sectioned, as previously described . Spinal cord segments, DRG, and STG were collected, bilaterally, from thoracic (T) 10 through S3 or coccygeal (CG) 1 vertebral levels, when ganglia were present.…”

Section: Methodsmentioning

confidence: 99%

“…Tissues were collected, fixed by immersion, and sectioned, as previously described. 11,12 Spinal cord segments, DRG, and STG were collected, bilaterally, from thoracic (T) 10 through S3 or coccygeal (CG) 1 vertebral levels, when ganglia were present. Not all DRGs were present due to surgical transection-induced die back, and not all STG were present bilaterally either due to the irregular nature of canine STG, die back, or both (numbers of ganglia collected per segment and group is reported in Supplemetray Information Tables).…”

Section: Euthanasia and Tissue Collectionmentioning

confidence: 99%

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Bladder reinnervation by somatic nerve transfer to pelvic nerve vesical branches does not reinnervate the urethra

Barbe¹,

Braverman²,

Salvadeo³

et al. 2019

Neurourology and Urodynamics

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Aims:We sought to determine whether somatic lumbar nerve transfer to the pelvic nerve's anterior vesical branch after sacral decentralization for detrusor muscle reinnervation also leads to aberrant innervation of the bladder outlet. Methods: Twenty-six female mongrel hound dogs underwent transection of sacral dorsal and ventral spinal roots (ie, sacral decentralization). Immediately afterward, 12 received genitofemoral nerve transfer and 9 received femoral nerve branch transfer. Five were left sacrally decentralized. Controls included 3 sham-operated and 6 unoperated. Eight months postsurgery, the bladder and urethra were injected with retrograde tracing dyes cystoscopically. After 3 weeks, detrusor and urethral pressures were assayed electrophysiologically immediately before euthanasia and characterization of neural reinnervation. Results: Electrical stimulation of spinal cords or roots did not lead to increased urethral sphincter pressure in nerve transfer animals, compared with decentralized animals, confirming a lack of functional reinnervation of the bladder outlet. In contrast, mean detrusor pressure increased after lumbar cord/root stimulation. In sham/unoperated animals, urethral and bladder dye injections resulted in labeled neurons in sacral level neural structures (dorsal root ganglia [DRG], sympathetic trunk ganglia [STG], and spinal cord ventral horns); labeling absent in decentralized animals. Urethral dye injections did not result in labeling in lumbar or sacral level neural structures in either nerve transfer group while bladder dye injections lead to increased labeled neurons in lumbar level DRG, STG, and ventral horns, compared to sacrally decentralized animals. Conclusion: Pelvic nerve transfer for bladder reinnervation does not impact urethral sphincter innervation.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Euthanasia and Tissue Collectionmentioning

confidence: 99%

See 2 more Smart Citations

Bladder reinnervation by somatic nerve transfer to pelvic nerve vesical branches does not reinnervate the urethra

Barbe¹,

Braverman²,

Salvadeo³

et al. 2019

Neurourology and Urodynamics

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“…In preclinical in vivo studies, the neural control of tissues or organs has been generally assessed by electrical stimulation of the major nerve innervating the region of interest. Functional reinnervation of bladder was evaluated in canine models of SCI by electrical stimulation of the pelvic plexus followed by monitoring detrusor muscle contraction and increase in bladder pressure 244,245 . In musculoskeletal traumarelated studies, reinnervation of injured muscle was assessed by measuring isometric muscle contraction force upon neural stimulation along with monitoring changes in gait pattern over time 246 .…”

Section: Challenges and Advancements Towards Fabricating Innervated Tmentioning

confidence: 99%

Innervation: the missing link for biofabricated tissues and organs

et al. 2020

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Innervation plays a pivotal role as a driver of tissue and organ development as well as a means for their functional control and modulation. Therefore, innervation should be carefully considered throughout the process of biofabrication of engineered tissues and organs. Unfortunately, innervation has generally been overlooked in most non-neural tissue engineering applications, in part due to the intrinsic complexity of building organs containing heterogeneous native cell types and structures. To achieve proper innervation of engineered tissues and organs, specific host axon populations typically need to be precisely driven to appropriate location(s) within the construct, often over long distances. As such, neural tissue engineering and/or axon guidance strategies should be a necessary adjunct to most organogenesis endeavors across multiple tissue and organ systems. To address this challenge, our team is actively building axon-based "living scaffolds" that may physically wire in during organ development in bioreactors and/or serve as a substrate to effectively drive targeted long-distance growth and integration of host axons after implantation. This article reviews the neuroanatomy and the role of innervation in the functional regulation of cardiac, skeletal, and smooth muscle tissue and highlights potential strategies to promote innervation of biofabricated engineered muscles, as well as the use of "living scaffolds" in this endeavor for both in vitro and in vivo applications. We assert that innervation should be included as a necessary component for tissue and organ biofabrication, and that strategies to orchestrate host axonal integration are advantageous to ensure proper function, tolerance, assimilation, and bio-regulation with the recipient post-implant.

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Dog and human bladders have different neurogenic and nicotinic responses in inner versus outer detrusor muscle layers

Frara

Barbe

Giaddui

et al. 2022

American Journal of Physiology-Regulatory, Integrative and Comp

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Aims: To investigate layer and species variations in detrusor muscle strip responses to myogenic, neurogenic, and nicotinic and muscarinic receptor stimulations. Methods: Strips from bladders of 9 dogs and 6 human organ transplant donors were dissected from inner and outer longitudinal muscle layers, at least 1 cm above urethral orifices. Strips were mounted in muscle baths and maximal responses to neurogenic stimulation using electrical field stimulation (EFS) and myogenic stimulation using potassium chloride (KCl, 120 mM) determined. After washing and re-equilibration, responses to nicotinic receptor agonist epibatidine (10μM) were determined, followed by responses to EFS and muscarinic receptor agonist bethanechol (30μM) in continued presence of epibatidine. Thereafter, strips and full thickness bladder sections from 4 additional dogs and 3 human donors were examined for axonal density and intramural ganglia. Results: In dog bladders, contractions to KCl, epibatidine, and bethanechol were 1.5- to 2-fold higher in the inner longitudinal muscle layer, while contractions to EFS were 1.5-fold higher in the outer (both pre- and post-epibatidine). Human bladders showed 1.2-fold greater contractions to epibatidine in the inner layer, and to EFS in the outer, yet no layer differences to KCl or bethanechol. In both species, axonal density was 2- to 2.5-fold greater in the outer layer. Dogs had more intramural ganglia in the adventitia/serosa layer, compared to more internal layers and to humans. Conclusions: These findings indicate several layer-dependent differences in receptor expression or distribution, and neurogenic responses in dog and human detrusor muscles, and myogenic/muscarinic differences between dog versus humans.

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Determining integrity of bladder innervation and smooth muscle function 1 year after lower spinal root transection in canines

Cited by 9 publications

References 12 publications

Bladder reinnervation by somatic nerve transfer to pelvic nerve vesical branches does not reinnervate the urethra

Bladder reinnervation by somatic nerve transfer to pelvic nerve vesical branches does not reinnervate the urethra

Innervation: the missing link for biofabricated tissues and organs

Dog and human bladders have different neurogenic and nicotinic responses in inner versus outer detrusor muscle layers

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