Validation of a methodology for neuro-urological and lumbosacral stimulation studies in domestic pigs: a humanlike animal model

2019 ◽  
Vol 30 (5) ◽  
pp. 644-654 ◽  
Author(s):  
Thomas Guiho ◽  
Christine Azevedo-Coste ◽  
David Guiraud ◽  
Claire Delleci ◽  
Grégoire Capon ◽  
...  

OBJECTIVESpinal cord injuries (SCIs) result in loss of movement and sensory feedback, but also organ dysfunction. Nearly all patients with complete SCI lose bladder control and are prone to kidney failure if intermittent catheterization is not performed. Electrical stimulation of sacral spinal roots was initially considered to be a promising approach for restoring continence and micturition control, but many patients are discouraged by the need for surgical deafferentation as it could lead to a loss of sensory functions and reflexes. Nevertheless, recent research findings highlight the renewed interest in spinal cord stimulation (SCS). It is thought that synergic recruitment of spinal fibers could be achieved by stimulating the spinal neural networks involved in regulating physiological processes. Paradoxically, most of these recent studies focused on locomotor issues, while few addressed visceral dysfunction. This could at least partially be attributed to the lack of methodological tools. In this study, the authors aim to fill this gap by presenting a comprehensive method for investigating the potential of SCS to restore visceral functions in domestic pigs, a large-animal model considered to be a close approximation to humans.METHODSThis methodology was tested in 7 female pigs (Landrace pig breed, 45–60 kg, 4 months old) during acute experiments. A combination of morphine and propofol was used for anesthesia when transurethral catheterization and lumbosacral laminectomy (L4–S4) were performed. At the end of the operation, spinal root stimulation (L6–S5) and urodynamic recordings were performed to compare the evoked responses with those observed intraoperatively in humans.RESULTSNervous excitability was preserved despite long-term anesthesia (mean 8.43 ± 1.5 hours). Transurethral catheterization and conventional laminectomy were possible while motor responses (gluteus muscle monitoring) were unaffected throughout the procedure. Consistent detrusor (approximately 25 cm H2O) and sphincter responses were obtained, whereas spinal root stimulation elicited detrusor and external urethral sphincter co-contractions similar to those observed intraoperatively in humans.CONCLUSIONSPigs represent an ideal model for SCS studies aimed at visceral function investigation and restoration because of the close similarities between female domestic pigs and humans, both in terms of anatomical structure and experimental techniques implemented. This article provides methodological keys for conducting experiments with equipment routinely used in clinical practice.

Author(s):  
Thomas Guiho ◽  
Christine Azevedo Coste ◽  
Claire Delleci ◽  
Jean-Patrick Chenu ◽  
Jean-Rodolphe Vignes ◽  
...  

Spinal cord injuries (SCI) result in the loss of movement and sensory feedback as well as organs dysfunctions. For example, nearly all SCI subjects loose their bladder control and are prone to kidney failure if they do not proceed to intermittent (self-) catheterization. Electrical stimulation of the sacral spinal roots with an implantable neuroprosthesis is a promising approach, with commercialized products, to restore continence and control micturition. However, many persons do not ask for this intervention since a surgical deafferentation is needed and the loss of sensory functions and reflexes become serious side effects of this procedure. Recent results renewed interest in spinal cord stimulation. Stimulation of existing pre-cabled neural networks involved in physiological processes regulation is suspected to enable synergic recruitment of spinal fibers. The development of direct spinal stimulation strategies aiming at bladder and bowel functions restoration would therefore appear as a credible alternative to existent solutions. However, a lack of suitable large animal model complicates these kinds of studies. In this article, we propose a new animal model of spinal stimulation -pig- and will briefly introduce results from one first acute experimental validation session.


2021 ◽  
Author(s):  
Zheng Cao ◽  
Weitao Man ◽  
Yuhui Xiong ◽  
Yi Guo ◽  
Shuhui Yang ◽  
...  

Abstract A hierarchically aligned fibrin hydrogel (AFG) that possesses soft stiffness and aligned nanofiber structure has been successfully proven to facilitate neuroregeneration in vitro and in vivo. However, its potential in promoting nerve regeneration in large animal models that is critical for clinical translation has not been sufficiently specified. Here, the effects of AFG on directing neuroregeneration in canine hemisected T12 spinal cord injuries were explored. Histologically obvious white matter regeneration consisting of a large area of consecutive, compact, and aligned nerve fibers is induced by AFG, leading to a significant motor functional restoration. The canines with AFG implantation start to stand well with their defective legs from 3 to 4 weeks postoperatively and even effortlessly climb the steps from 7 to 8 weeks. Moreover, high-resolution multi-shot diffusion tensor imaging illustrates the spatiotemporal dynamics of nerve regeneration rapidly crossing the lesion within 4 weeks in the AFG group. Our findings indicate that AFG could be a potential therapeutic vehicle for spinal cord injury by inducing rapid white matter regeneration and restoring locomotion, pointing out its promising prospect in clinic practice.


2010 ◽  
Vol 33 (1) ◽  
pp. 43-57 ◽  
Author(s):  
John Kuluz ◽  
Amer Samdani ◽  
David Benglis ◽  
Manuel Gonzalez-Brito ◽  
Juan P. Solano ◽  
...  

Author(s):  
Mark Züchner ◽  
Manuel J. Escalona ◽  
Lena Hammerlund Teige ◽  
Evangelos Balafas ◽  
Lili Zhang ◽  
...  

Spinal cord injury (SCI) is a medically, psychologically and socially disabling condition. A large body of our knowledge on the basic mechanisms of SCI has been gathered in rodents. For preclinical validation of promising therapies, the use of animal models that are closer to humans has several advantages. This has promoted a more intensive development of large animal models for SCI during the past decade. We have recently developed a multimodal SCI apparatus for large animals that generated biomechanically reproducible impacts in vivo. It is composed of a spring-load impactor and support systems for the spinal cord and the vertebral column. We now present the functional outcome of farm pigs and minipigs injured with different lesion strengths. There was a correlation between the biomechanical characteristics of the impact, the functional outcome, and the tissue damage observed several weeks after injury. We also provide a detailed description of the procedure to generate such a SCI in both farm pigs and minipigs, in the hope to ease the adoption of the swine model by other research groups.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Seth Tigchelaar ◽  
Femke Streijger ◽  
Sunita Sinha ◽  
Stephane Flibotte ◽  
Neda Manouchehri ◽  
...  

2012 ◽  
Vol 29 (5) ◽  
pp. 1000-1011 ◽  
Author(s):  
Theda Marie Anne Boekhoff ◽  
Eva-Maria Ensinger ◽  
Regina Carlson ◽  
Patricia Bock ◽  
Wolfgang Baumgärtner ◽  
...  

2008 ◽  
Vol 25 (5) ◽  
pp. E3 ◽  
Author(s):  
Rachid Assina ◽  
Tejas Sankar ◽  
Nicholas Theodore ◽  
Sam P. Javedan ◽  
Alan R. Gibson ◽  
...  

Object Axonal regeneration may be hindered following spinal cord injury (SCI) by a limited immune response and insufficient macrophage recruitment. This limitation has been partially surmounted in small-mammal models of SCI by implanting activated autologous macrophages (AAMs). The authors sought to replicate these results in a canine model of partial SCI. Methods Six dogs underwent left T-13 spinal cord hemisection. The AAMs were implanted at both ends of the lesion in 4 dogs, and 2 other dogs received sham implantations of cell media. Cortical motor evoked potentials (MEPs) were used to assess electrophysiological recovery. Functional motor recovery was assessed with a modified Tarlov Scale. After 9 months, animals were injected with wheat germ agglutinin–horseradish peroxidase at L-2 and killed for histological assessment. Results Three of the 4 dogs that received AAM implants and 1 of the 2 negative control dogs showed clear recovery of MEP response. Behavioral assessment showed no difference in motor function between the AAM-treated and control groups. Histological investigation with an axonal retrograde tracer showed neither local fiber crossing nor significant uptake in the contralateral red nucleus in both implanted and negative control groups. Conclusions In a large-animal model of partial SCI treated with implanted AAMs, the authors saw no morphological or histological evidence of axonal regeneration. Although they observed partial electrophysiological and functional motor recovery in all dogs, this recovery was not enhanced in animals treated with implanted AAMs. Furthermore, there was no morphological or histological evidence of axonal regeneration in animals with implants that accounted for the observed recovery. The explanation for this finding is probably multifactorial, but the authors believe that the AAM implantation does not produce axonal regeneration, and therefore is a technology that requires further investigation before it can be clinically relied on to ameliorate SCI.


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