A PERIPHERAL NERVE INJURY MODEL UTILIZING A SIMPLE TISSUE SPARING APPROACH TO THE RABBIT SCIATIC NERVE

2018 ◽  
Vol 21 (01) ◽  
pp. 1850002
Author(s):  
Andrew J. Miller ◽  
Jacob Tulipan ◽  
Mark Wang ◽  
Pedro Beredjiklian ◽  
Andrzej Fertala ◽  
...  

Background & Aims: Peripheral nerve injury models require a reproducible surgical technique that provides a simple and extensile peripheral nerve exposure. We present a muscle sparing apprach to the sciatic nerve in a rabbit model. A combination of general anestheia, sedative and perioperative analgesics was given to minimize animal discomfort. Methods: A posterior lateral dissection of the rabbit hind leg was performed to expose the proximal sciatic nerve. This facilitated an extensile dissection of both the proximal and distal sciatic nerve. Results: The described dissection is atraumatic, bloodless, and yields minimal postoperative morbidity on the rabbit. All rabbits received standard postoperative care in compliance with all regulatory agencies. A full vetinarian staff was available to manage the animals postoperatively. Conclusion: We found that our technique is a reproducible and easy to perform surgical approach with basic surgical setup. Our animal model provides an opportunity to evaluate and study peripheral nerve injuries peripheral nerve injuries.

2011 ◽  
Vol 106 (5) ◽  
pp. 2450-2470 ◽  
Author(s):  
Francisco J. Alvarez ◽  
Haley E. Titus-Mitchell ◽  
Katie L. Bullinger ◽  
Michal Kraszpulski ◽  
Paul Nardelli ◽  
...  

Motor and sensory proprioceptive axons reinnervate muscles after peripheral nerve transections followed by microsurgical reattachment; nevertheless, motor coordination remains abnormal and stretch reflexes absent. We analyzed the possibility that permanent losses of central IA afferent synapses, as a consequence of peripheral nerve injury, are responsible for this deficit. VGLUT1 was used as a marker of proprioceptive synapses on rat motoneurons. After nerve injuries synapses are stripped from motoneurons, but while other excitatory and inhibitory inputs eventually recover, VGLUT1 synapses are permanently lost on the cell body (75–95% synaptic losses) and on the proximal 100 μm of dendrite (50% loss). Lost VGLUT1 synapses did not recover, even many months after muscle reinnervation. Interestingly, VGLUT1 density in more distal dendrites did not change. To investigate whether losses are due to VGLUT1 downregulation in injured IA afferents or to complete synaptic disassembly and regression of IA ventral projections, we studied the central trajectories and synaptic varicosities of axon collaterals from control and regenerated afferents with IA-like responses to stretch that were intracellularly filled with neurobiotin. VGLUT1 was present in all synaptic varicosities, identified with the synaptic marker SV2, of control and regenerated afferents. However, regenerated afferents lacked axon collaterals and synapses in lamina IX. In conjunction with the companion electrophysiological study [Bullinger KL, Nardelli P, Pinter MJ, Alvarez FJ, Cope TC. J Neurophysiol (August 10, 2011). doi:10.1152/jn.01097.2010], we conclude that peripheral nerve injuries cause a permanent retraction of IA afferent synaptic varicosities from lamina IX and disconnection with motoneurons that is not recovered after peripheral regeneration and reinnervation of muscle by sensory and motor axons.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Shimon Rochkind ◽  
Zvi Nevo

Objective. Guiding Regeneration Gel (GRG) was developed in response to the clinical need of improving treatment for peripheral nerve injuries and helping patients regenerate massive regional losses in peripheral nerves. The efficacy of GRG based on tissue engineering technology for the treatment of complete peripheral nerve injury with significant loss defect was investigated.Background. Many severe peripheral nerve injuries can only be treated through surgical reconstructive procedures. Such procedures are challenging, since functional recovery is slow and can be unsatisfactory. One of the most promising solutions already in clinical practice is synthetic nerve conduits connecting the ends of damaged nerve supporting nerve regeneration. However, this solution still does not enable recovery of massive nerve loss defect.The proposed technologyis a biocompatible and biodegradable gel enhancing axonal growth and nerve regeneration. It is composed of a complex of substances comprising transparent, highly viscous gel resembling the extracellular matrix that is almost impermeable to liquids and gasses, flexible, elastic, malleable, and adaptable to various shapes and formats.Preclinical studyon rat model of peripheral nerve injury showed that GRG enhanced nerve regeneration when placed in nerve conduits, enabling recovery of massive nerve loss, previously unbridgeable, and enabled nerve regeneration at least as good as with autologous nerve graft “gold standard” treatment.


2021 ◽  
Vol 7 ◽  
Author(s):  
Shimon Rochkind ◽  
Mara Almog ◽  
Sigal Meilin ◽  
Zvi Nevo

Background and Aims: The aim of this study was to investigate the innovative guiding regenerative gel (GRG) and antigliotic GRG (AGRG) fillings for nerve conduits, prepared with Food and Drug Administration (FDA)-approved agents and expected to provide an alternative to autologous nerve graft and to enable reconnection of massive nerve gaps in a rabbit model of chronic peripheral nerve injury with massive loss defect that simulates the human condition of chronic injury with a large gap.Methods: The components and dosimetry for GRG and AGRG formulations were investigated in vitro on nerve cell culture and in vivo on 10-mm reconstructed sciatic nerves of 72 rats using different concentrations of agents and completed on a rabbit model of delayed (chronic) complete peripheral nerve injury with a 25-mm gap. Forty rabbits underwent delayed (9 weeks after complete injury of the tibial portion of the sciatic nerve) nerve tube reconstruction of a gap that is 25 mm long. GRG and AGRG groups were compared with autologous and empty tube reconstructed groups. Rats and rabbits underwent electrophysiological and histochemical assessments (19 weeks for rats and 40 weeks for rabbits).Results: Application of AGRG showed a significant increase of about 78% in neurite length per cell and was shown to have the most promising effect on neuronal outgrowth, with total number of neurites increasing by 4-fold. The electrophysiological follow-up showed that AGRG treatment is most promising for the reconstruction of the tibial portion of the sciatic nerve with a critical gap of 25 mm. The beneficial effect of AGRG was found when compared with the autologous nerve graft reconstruction. Thirty-one weeks post the second surgery (delayed reconstruction), histochemical observation showed significant regeneration after using AGRG neurogel, compared with the empty tube, and succeeded in significantly regenerating the nerve, as well as the autologous nerve graft, which was almost similar to a healthy nerve.Conclusion: We demonstrate that in the model of delayed peripheral nerve repair with massive loss defect, the application of AGRG led to a stronger nerve recovery and can be an alternative to autologous nerve graft.


2022 ◽  
Vol 10 (A) ◽  
pp. 1-5
Author(s):  
Riki Sukiandra ◽  
Eti Yerizel ◽  
Yuliarni Syafrita ◽  
Eryati Darwin

BACKGROUND: Interleukin-6 (IL-6) and inducible Nitric oxide Synthase (iNOS) have an effect on neuropathic pain in the inflammatory process in peripheral nerve injuries. AIM: This study aims to examine the effect of anti-IL-6 receptor antibody on IL-6 and iNOS levels as a consideration for the treatment of neuropathic pain in a rat model of peripheral nerve injury. METHODS: Twenty-eight young adult male Wistar rats were treated for peripheral nerve injury and then divided into two groups. Fourteen treatment groups (Group P) were given anti-IL-6 receptor antibody by injection at a dose of 100 g/day by injection into the saphenous vein in the rat’s leg for 3 days. In both groups, the serum IL-6 and iNOS levels were assessed on the 3rd day after administration of anti-IL-6 receptor antibody in group P, using the sandwich ELISA method. RESULTS: The results showed that the administration of anti-IL-6 receptor antibody did not have a significant effect on reducing IL-6 and iNOS levels in group P (p > 0.05). Administration of anti-IL-6 receptor antibody had more effect on IL-6 levels on iNOS levels, where a decrease in IL-6 levels caused a decrease in iNOS levels in group P (p = 0.004 and r = 0.693). CONCLUSIONS: We conclude that the present administration of anti-IL-6 receptor antibody cannot be considered as a treatment for neuropathic pain in peripheral nerve injuries, but can be used to influence IL-6 levels on iNOS levels.


Author(s):  
M. DESCHRIJVER ◽  
K. BULKMANS ◽  
I. VANWALLEGHEM ◽  
S. GEERS

Peripheral nerve injury and the effect of vitamins on the recovery process Although peripheral nerve injuries are usually not life-threatening, they can have a significant impact on the patient’s quality of life and daily functioning, with typical symptoms such as complete paralysis or severe neuropathic pain. The peripheral nervous system is capable of some regeneration and recovery, allowing conservative treatment in mild to moderate nerve damage. For severe peripheral nerve injuries surgical reconstruction remains the golden standard. However, despite the extensive knowledge of the pathophysiology of peripheral nerve trauma, a full functional recovery after a severe peripheral nerve injury is rare with the current therapeutic options. Success depends on a variety of factors: location and severity of the injury, age and physical condition of the patient, therapeutical approach, … Therefore, it is important to search for the best possible means to achieve maximal functional recovery. This article first discusses the current knowledge about the pathophysiology of peripheral nerve trauma, highlighting the most important factors that influence the recovery process. Subsequently, it will render a review of the influence of vitamins A/B/C/D/E/K on this recovery process: vit B and D seem to enhance the regeneration process of nerves and the functional recovery of the end organ, while vit C and E show an important antinociceptive effect.


2021 ◽  
pp. 127-132
Author(s):  
Luka Androja ◽  
Josip Miočić ◽  
Žarko Bilić ◽  
Milica Komšo

Peripheral nerves in athletes are susceptible to injury due to an increase in physiological requirements in the training process to neurological structures and to the soft tissues that protect them. The training process is conditioned by the rank and level of competition and its implementation largely depends on the education of professional staff. Common mechanisms of injury are pressure, sprain, strain, ischemia, and sports injury. Seddon's original system of dividing nerve injuries based on neurophysiological changes is most widely used in medicine. The initial stage of nerve injury is neuropraxia, the second stage is axonal degeneration, and the third stage is nerve cutting. Peripheral nerve injuries are more common in the upper extremities than in the lower extremities. They have specifics related to a particular sport, in this case, football and basketball, and often have a biomechanical component in the making. Early detection allows an appropriate rehabilitation program to be initiated and biomechanics changed before the nerve injury becomes permanent. Recognizing nerve injury requires an understanding of peripheral neuroanatomy, knowledge of common nerve injury sites, and awareness of the types of peripheral nerve injuries that are common and specific to a particular sport. Rehabilitation programs in the field of kinesiology can be read through FMS protocols. Electrodiagnostic tests (electromyography), somatosensory evoked potentials, magnetic resonance imaging, and ultrasound are used to diagnose peripheral nerve injuries. Proximal peripheral nerve injuries have a slightly poorer prognosis in terms of neurological recovery in athletes. The survey determined the frequency of injuries in the subjects and that there is a misunderstanding among the athletes themselves, which is a peripheral nerve injury. The survey also found that peripheral nerve injuries occur due to acute injuries, while chronic injuries are excessive, resulting in damage to muscles and joints, and rarely as a result of inappropriate sports equipment. Athletes' knowledge of what constitutes a peripheral nerve injury itself and how this type of injury should be given more importance in further general prevention has also been established.


Hand Surgery ◽  
2010 ◽  
Vol 15 (03) ◽  
pp. 173-176
Author(s):  
F. Ya'ish ◽  
J. P. Cooper ◽  
M. A. Craigen

The clinical assessment of patients with peripheral nerve injury is primarily dependent on subjective clinical examination. We aimed to assess whether a thermotropic liquid crystal ring (TLC-ring) could provide the basis for an objective assessment of peripheral nerve injury by detecting temperature changes in the digits innervated by the damaged nerve. A group of patients with known median, ulnar or both digital nerve injuries were compared against a control group. TLC-rings, marketed to the general public as "mood rings", were applied to the affected and unaffected digits and the colour change recorded. Areas with nerve damage showed a statistically significant difference in colour response to those without damage. This study establishes the ability of TLCs to detect cutaneous temperature changes associated with peripheral nerve injuries. Further studies and improvements are needed to refine TLC as an acute assessment tool for peripheral nerve injuries.


Author(s):  
Hendita Maulida

Peripheral nerve injury with a gap of 5–30 mm can cause permanent paralysis because it causes an axon to break up. The distance between axons of more than 1-2 cm requires a graft in the form of a nerve connector to fix it. Synthesis of chitosan coated polyurethane-collagen hollowfiber has been carried out as an accelerator for healing peripheral nerve injury. The results of Fourier Transform Infra Red (FTIR) analysis showed a cross link between chitosan and glutaraldehyde seen in the shift of wave numbers from 1080-1100 cm-1 to 1002 cm-1. The degradation test results showed that the sample experienced a decrease in mass after being immersed in Simulated Body Fluid (SBF) for 7 days. Polyurethane can be degraded in the body after 30 days. This is in accordance with the mechanism of the nerve which regenerates 1 mm per day or 1 inch per month. Scanning Electron Microscope (SEM) analysis showed that the diameter of the hollowfiber was 2.021-2.032 mm which corresponds to the peripheral nerve diameter of 1.5-3 mm and the pore size of the wall is 31.33-39.65 μm. The results of this study are expected to provide the theoretical basis for the use of chitosan polyurethane-collagen coating composites as nerve grafts for the treatment of peripheral nerve injuries that have biocompatible properties, can regenerate and are easily degraded and provide alternative solutions for nerve graft needs that are more economical and easier to manufacture so widely produced in Indonesia.


2002 ◽  
Vol 87 (4) ◽  
pp. 1763-1771 ◽  
Author(s):  
Antoni Valero-Cabré ◽  
Xavier Navarro

We investigated the changes induced in crossed extensor reflex responses after peripheral nerve injury and repair in the rat. Adults rats were submitted to non repaired sciatic nerve crush (CRH, n = 9), section repaired by either aligned epineurial suture (CS, n = 11) or silicone tube (SIL4, n = 13), and 8 mm resection repaired by tubulization (SIL8, n = 12). To assess reinnervation, the sciatic nerve was stimulated proximal to the injury site, and the evoked compound muscle action potential (M and H waves) from tibialis anterior and plantar muscles and nerve action potential (CNAP) from the tibial nerve and the 4th digital nerve were recorded at monthly intervals for 3 mo postoperation. Nociceptive reinnervation to the hindpaw was also assessed by plantar algesimetry. Crossed extensor reflexes were evoked by stimulation of the tibial nerve at the ankle and recorded from the contralateral tibialis anterior muscle. Reinnervation of the hindpaw increased progressively with time during the 3 mo after lesion. The degree of muscle and sensory target reinnervation was dependent on the severity of the injury and the nerve gap created. The crossed extensor reflex consisted of three bursts of activity (C1, C2, and C3) of gradually longer latency, lower amplitude, and higher threshold in control rats. During follow-up after sciatic nerve injury, all animals in the operated groups showed recovery of components C1 and C2 and of the reflex H wave, whereas component C3 was detected in a significantly lower proportion of animals in groups with tube repair. The maximal amplitude of components C1 and C2 recovered to values higher than preoperative values, reaching final levels between 150 and 245% at the end of the follow-up in groups CRH, CS, and SIL4. When reflex amplitude was normalized by the CNAP amplitude of the regenerated tibial nerve, components C1 (300–400%) and C2 (150–350%) showed highly increased responses, while C3 was similar to baseline levels. In conclusion, reflexes mediated by myelinated sensory afferents showed, after nerve injuries, a higher degree of facilitation than those mediated by unmyelinated fibers. These changes tended to decline toward baseline values with progressive reinnervation but still remained significant 3 mo after injury.


2021 ◽  
Vol 17 ◽  
pp. 174480692110066
Author(s):  
Orest Tsymbalyuk ◽  
Volodymyr Gerzanich ◽  
Aaida Mumtaz ◽  
Sanketh Andhavarapu ◽  
Svetlana Ivanova ◽  
...  

Background Neuropathic pain following peripheral nerve injury (PNI) is linked to neuroinflammation in the spinal cord marked by astrocyte activation and upregulation of interleukin 6 (IL -6 ), chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-X-C motif) ligand 1 (CXCL1), with inhibition of each individually being beneficial in pain models. Methods Wild type (WT) mice and mice with global or pGfap-cre- or pGFAP-cre/ERT2-driven Abcc8/SUR1 deletion or global Trpm4 deletion underwent unilateral sciatic nerve cuffing. WT mice received prophylactic (starting on post-operative day [pod]-0) or therapeutic (starting on pod-21) administration of the SUR1 antagonist, glibenclamide (10 µg IP) daily. We measured mechanical and thermal sensitivity using von Frey filaments and an automated Hargreaves method. Spinal cord tissues were evaluated for SUR1-TRPM4, IL-6, CCL2 and CXCL1. Results Sciatic nerve cuffing in WT mice resulted in pain behaviors (mechanical allodynia, thermal hyperalgesia) and newly upregulated SUR1-TRPM4 in dorsal horn astrocytes. Global and pGfap-cre-driven Abcc8 deletion and global Trpm4 deletion prevented development of pain behaviors. In mice with Abcc8 deletion regulated by pGFAP-cre/ERT2, after pain behaviors were established, delayed silencing of Abcc8 by tamoxifen resulted in gradual improvement over the next 14 days. After PNI, leakage of the blood-spinal barrier allowed entry of glibenclamide into the affected dorsal horn. Daily repeated administration of glibenclamide, both prophylactically and after allodynia was established, prevented or reduced allodynia. The salutary effects of glibenclamide on pain behaviors correlated with reduced expression of IL-6, CCL2 and CXCL1 by dorsal horn astrocytes. Conclusion SUR1-TRPM4 may represent a novel non-addicting target for neuropathic pain.


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