scholarly journals Covering the proximal nerve stump with chondroitin sulfate proteoglycans prevents traumatic painful neuroma formation by blocking axon regeneration after neurotomy in Sprague Dawley rats

2020 ◽  
pp. 1-11
Author(s):  
Fu-Lin He ◽  
Shuai Qiu ◽  
Jian-Long Zou ◽  
Fan-Bin Gu ◽  
Zhi Yao ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Axon Regeneration ◽  
Scar Tissue ◽  
Chondroitin Sulfate Proteoglycans ◽  
Sprague Dawley ◽  
Nerve Stump ◽  
Related Factors ◽  
Positive Group ◽  
Sprague Dawley Rats ◽  
Neuroma Formation

OBJECTIVENeuropathic pain caused by traumatic neuromas is an extremely intractable clinical problem. Disorderly scar tissue accumulation and irregular and immature axon regeneration around the injury site mainly contribute to traumatic painful neuroma formation. Therefore, successfully preventing traumatic painful neuroma formation requires the effective inhibition of irregular axon regeneration and disorderly accumulation of scar tissue. Considering that chondroitin sulfate proteoglycans (CSPGs) can act on the growth cone and effectively inhibit axon regeneration, the authors designed and manufactured a CSPG-gelatin blocker to regulate the CSPGs’ spatial distribution artificially and applied it in a rat model after sciatic nerve neurectomy to evaluate its effects in preventing traumatic painful neuroma formation.METHODSSixty female Sprague Dawley rats were randomly divided into three groups (positive group: no covering; blank group: covering with gelatin blocker; and CSPG group: covering with the CSPG-gelatin blocker). Pain-related factors were evaluated 2 and 8 weeks postoperatively (n = 30). Neuroma growth, autotomy behavior, and histological features of the neuromas were assessed 8 weeks postoperatively (n = 30).RESULTSEight weeks postoperatively, typical bulb-shaped neuromas did not form in the CSPG group, and autotomy behavior was obviously better in the CSPG group (p < 0.01) than in the other two groups. Also, in the CSPG group the regenerated axons showed a lower density and more regular and improved myelination (p < 0.01). Additionally, the distribution and density of collagenous fibers and the expression of α–smooth muscle actin were significantly lower in the CSPG group than in the positive group (p < 0.01). Regarding pain-related factors, c-fos, substance P, interleukin (IL)–17, and IL-1β levels were significantly lower in the CSPG group than those in the positive and blank groups 2 weeks postoperatively (p < 0.05), while substance P and IL-17 remained lower in the CSPG group 8 weeks postoperatively (p < 0.05).CONCLUSIONSThe authors found that CSPGs loaded in a gelatin blocker can prevent traumatic neuroma formation and effectively relieve pain symptoms after sciatic nerve neurotomy by blocking irregular axon regeneration and disorderly collagenous fiber accumulation in the proximal nerve stump. These results indicate that covering the proximal nerve stump with CSPGs may be a new and promising strategy to prevent traumatic painful neuroma formation in the clinical setting.

Side-to-Side Nerve Grafts Sustain Chronically Denervated Peripheral Nerve Pathways During Axon Regeneration and Result in Improved Functional Reinnervation

Neurosurgery ◽  
2011 ◽  
Vol 68 (6) ◽  
pp. 1654-1666 ◽  
Author(s):  
Adil Ladak ◽  
Paul Schembri ◽  
Jaret Olson ◽  
Esther Udina ◽  
Neil Tyreman ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Axon Regeneration ◽  
Surgical Repair ◽  
Progressive Failure ◽  
Nerve Repair ◽  
Sprague Dawley ◽  
Nerve Stump ◽  
Sprague Dawley Rats ◽  
Distal Nerve ◽  
And Control

Abstract BACKGROUND: Progressive atrophy of Schwann cells in denervated nerve stumps is a major reason for progressive failure of functional recovery after peripheral nerve injury and surgical repair. OBJECTIVE: To examine whether side-to-side nerve bridges between an intact donor nerve and a recipient denervated distal nerve stump promote nerve growth and in turn, protect distal nerve stumps to improve axon regeneration after delayed surgical repair. METHODS: In Sprague-Dawley rats, 1 or 3 side-to-side common peroneal (CP) nerve bridges were used to bridge between the donor intact tibial (TIB) nerve and a recipient denervated CP distal nerve stump in the contralateral hind limb. No bridges were placed in control animals. After 4 months, either a fluorescent retrograde dye was applied to back-label TIB motoneurons with axons that had grown into the CP nerve stump or the proximal and distal CP nerve stumps were resutured in experimental and control animals to encourage CP nerve regeneration for 5 months. Retrograde dyes were again applied to count CP motoneurons that regenerated their axons through protected and unprotected nerve stumps. RESULTS: Significantly more donor TIB motoneurons regenerated axons into the recipient denervated CP nerve stump through 3 side-to-side CP nerve bridges compared with 1 bridge. This TIB nerve protection significantly increased the number of CP motoneurons regenerating axons through the denervated CP nerve stumps, the number of regenerated axons, and the weight of the reinnervated muscles. CONCLUSION: Multiple side-to-side nerve bridges protect chronically denervated nerve stumps to improve axon regeneration and target reinnervation after delayed nerve repair.

scholarly journals Neuroma Prevention and Implantation Effects of NEUROCAP in Rat Sciatic Nerve Model

2021 ◽  
Vol 06 (01) ◽  
pp. e1-e10
Author(s):  
Steven L. Peterson ◽  
Harm de Vries ◽  
Kami Collins ◽  
Hilde Geraedts ◽  
Michael J. Wheatley
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Test Group ◽  
Control Group ◽  
Nerve Transection ◽  
Sprague Dawley ◽  
Rat Sciatic Nerve ◽  
Sprague Dawley Rats ◽  
Nerve Model ◽  
Neuroma Formation

Abstract Introduction Symptomatic neuroma with neuropathic pain can develop following peripheral nerve injury. Current interventions for symptomatic neuroma have unpredictable results. NEUROCAP (Polyganics, Groningen, The Netherlands) is a bioresorbable nerve capping device intended to protect a peripheral nerve end and separate the nerve from the surrounding environment, to prevent the recurrence of a symptomatic neuroma. Materials and Methods This study aims to assess the implantation effects of the NEUROCAP device in a rat sciatic nerve model during 12 months (±2 days). Forty-one adult male Sprague-Dawley rats were used in this study. They were randomly divided into a capping or test group, or a noncapping or control group for different time points of survival (12 weeks, 6 months, and 12 months). The objective of this study was evaluated regarding procedural data, adverse events, clinical observations, and histopathology. Results The overall general health of the animals was adequate throughout the study, with the exception of autotomy during the first 4 months of survival. Eight animals were euthanized early due to autotomy, excluded from the study and seven of them have been replaced. Autotomy was an expected outcome and a known limitation of the animal model, particularly as this was a full sciatic nerve transection model. Neuroma formation was observed in the control group while there was no neuroma formation present in the test group. The control group showed increased nerve outgrowth and more chaotic fascicles in comparison with the test group. The test group also had a higher percentage of myelinated fibers compared to the control group. These results indicate a preventive mode of action of the NEUROCAP with regard to neuroma formation after nerve transection in a rat sciatic nerve model. Conclusion The results indicate that NEUROCAP is safe and effective in preventing the recurrence of neuroma formation and inhibiting nerve outgrowth.

scholarly journals Effect of Nerve-Cutting Technique on Nerve Microstructure and Neuroma Formation

2018 ◽  
Vol 11 (01) ◽  
pp. 028-034
Author(s):  
Wayne Rummings ◽  
P. Honeycutt ◽  
Edward Jernigan ◽  
Paul Weinhold ◽  
Reid Draeger
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Sciatic Nerve ◽  
Clinical Importance ◽  
Sprague Dawley ◽  
Tongue Depressor ◽  
Cutting Guide ◽  
Scalpel Blade ◽  
Neuroma Formation ◽  
Scanning Electron

Abstract Background Peripheral neuroma formation results from partial or complete nerve division. Elucidating measures to prevent the development of peripheral neuromas is of clinical importance. The aim of this study was to determine the effect of various surgical nerve-cutting techniques on nerve microstructure and resultant neuroma formation. Methods Twenty Sprague-Dawley rats were randomly assigned to one of the following nerve-cutting techniques: No. 15 scalpel blade with tongue depressor, micro-serrated scissors, nerve-cutting guide forceps with straight razor, and bipolar cauterization. The right sciatic nerve was transected using the assigned nerve-cutting technique. Neuromas were harvested 6 weeks postoperatively, and samples were obtained for histologic analysis. The contralateral sciatic nerve was transected at euthanasia and analyzed with histology and with scanning electron microscopy in a subset of the rats. Results Fifteen of the 20 rats survived the 6-week experiment. Scanning electron microscopy of the No. 15 scalpel blade group showed the most visual damage and disorganization whereas the nerve-cutting guide forceps and micro-serrated scissors groups resulted in a smooth transected surface. Bipolar cauterization appeared to enclose the fascicular architecture within a sealed epineurium. Each neuroma was significantly larger than contralateral controls. There were no significant differences in neuroma caliber between nerve transection groups. No substantial differences in microstructure were evident between transection groups. Conclusion Despite disparate microscopic appearances of the cut surfaces of nerves using various nerve-cutting techniques, we found no significant differences in the caliber or incidence of neuroma formation based on nerve-cutting technique. Nerve-cutting technique used when transecting peripheral nerves may have little bearing on the formation or size of resultant neuroma formation.

Comparison of the Potency of Lidocaine and Chloroprocaine in Sciatic Nerve Block in Sprague-Dawley Rats

Pharmacology ◽  
2009 ◽  
Vol 83 (6) ◽  
pp. 356-359 ◽  
Author(s):  
Elliot Yung ◽  
Joel M. Yarmush ◽  
Jonathan Weinberg ◽  
Joseph J. SchianodiCola ◽  
Sidhartha D. Ray
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Sciatic Nerve Block ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

A biodegradable block polyurethane nerve-guidance scaffold enhancing rapid vascularization and promoting reconstruction of transected sciatic nerve in Sprague-Dawley rats

2020 ◽  
Vol 8 (48) ◽  
pp. 11063-11073
Author(s):  
Yuqing Niu ◽  
Massimiliano Galluzzi
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Schematic of nerve guidance scaffold for reconstruction of peripheral nerve defects in Sprague-Dawley rats.

Concurrent increases in regional hematocrit and blood flow in diabetic rats: prevention by sorbinil

1992 ◽  
Vol 263 (3) ◽  
pp. H945-H950 ◽  
Author(s):  
S. P. Sutera ◽  
K. Chang ◽  
J. Marvel ◽  
J. R. Williamson
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Sciatic Nerve ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Citrate Buffer ◽  
Ocular Tissues ◽  
Arterial Blood ◽  
Transit Times ◽  
Sprague Dawley Rats

These studies were undertaken to investigate the relationship between regional hemodynamic and hemorheological changes in the microvasculature of diabetic rats. Diabetes was induced in male Sprague-Dawley rats by injection of streptozotocin (55 mg/kg body wt). Control rats were injected with vehicle (sodium citrate buffer). A subgroup of diabetic rats was treated with an aldose reductase inhibitor (sorbinil) added to the diet in an amount to provide a daily dose of approximately 0.2 mmol.kg-1.day-1. Three weeks later all animals were anesthetized with thiobutabarbital sodium (Inactin, 100 mg/kg injected intraperitoneally) for assessment of blood flow (by injection of 15 microns microspheres) and regional hematocrit (determined by isotope-dilution techniques using 51Cr-labeled red blood cells and 125I-labeled bovine serum albumin) in selected tissues. The hematocrit in arterial blood samples was identical (approximately 46%) in controls and in diabetics. Regional hematocrits were much lower than arterial hematocrits in control rats and ranged from approximately 20% in ocular tissues, sciatic nerve, diaphragm, and skin to approximately 30% in brain, skeletal muscle, heart, and fat. Hematocrits of diabetic rats were markedly increased in ocular tissues, sciatic nerve, and skin but not in brain, heart, or skeletal muscle. These increases in regional hematocrit were associated with increases in blood flow and were largely prevented by sorbinil. Diabetes induced significant decreases in the mean transit times for whole blood and erythrocytes in all tissues examined except brain, retina, and skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury

2016 ◽  
Vol 25 (1) ◽  
pp. 114-124 ◽  
Author(s):  
Sergiy V. Kushchayev ◽  
Morgan B. Giers ◽  
Doris Hom Eng ◽  
Nikolay L. Martirosyan ◽  
Jennifer M. Eschbacher ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuroprotective Effect ◽  
Scar Tissue ◽  
Treated Group ◽  
Secondary Injury ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Cord Injury ◽  
Behavioral Assessments

OBJECTIVE Spinal cord injury occurs in 2 phases. The initial trauma is followed by inflammation that leads to fibrous scar tissue, glial scarring, and cavity formation. Scarring causes further axon death around and above the injury. A reduction in secondary injury could lead to functional improvement. In this study, hyaluronic acid (HA) hydrogels were implanted into the gap formed in the hemisected spinal cord of Sprague-Dawley rats in an attempt to attenuate damage and regenerate tissue. METHODS A T-10 hemisection spinal cord injury was created in adult male Sprague-Dawley rats; the rats were assigned to a sham, control (phosphate-buffered saline), or HA hydrogel–treated group. One cohort of 23 animals was followed for 12 weeks and underwent weekly behavioral assessments. At 12 weeks, retrograde tracing was performed by injecting Fluoro-Gold in the left L-2 gray matter. At 14 weeks, the animals were killed. The volume of the lesion and the number of cells labeled from retrograde tracing were calculated. Animals in a separate cohort were killed at 8 or 16 weeks and perfused for immunohistochemical analysis and transmission electron microscopy. Samples were stained using H & E, neurofilament stain (neurons and axons), silver stain (disrupted axons), glial fibrillary acidic protein stain (astrocytes), and Iba1 stain (mononuclear cells). RESULTS The lesions were significantly smaller in size and there were more retrograde-labeled cells in the red nuclei of the HA hydrogel–treated rats than in those of the controls; however, the behavioral assessments revealed no differences between the groups. The immunohistochemical analyses revealed decreased fibrous scarring and increased retention of organized intact axonal tissue in the HA hydrogel–treated group. There was a decreased presence of inflammatory cells in the HA hydrogel–treated group. No axonal or neuronal regeneration was observed. CONCLUSIONS The results of these experiments show that HA hydrogel had a neuroprotective effect on the spinal cord by decreasing the magnitude of secondary injury after a lacerating spinal cord injury. Although regeneration and behavioral improvement were not observed, the reduction in disorganized scar tissue and the retention of neurons near and above the lesion are important for future regenerative efforts. In addition, this gel would be useful as the base substrate in the development of a more complex scaffold.

scholarly journals Characterization of Diabetic Neuropathy in the Zucker Diabetic Sprague-Dawley Rat: A New Animal Model for Type 2 Diabetes

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Eric P. Davidson ◽  
Lawrence J. Coppey ◽  
Amey Holmes ◽  
Sergey Lupachyk ◽  
Brian L. Dake ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Animal Model ◽  
Sciatic Nerve ◽  
Diabetic Neuropathy ◽  
Elevated Serum ◽  
Nerve Fibers ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Corneal Nerves

Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley (ZDSD/Pco) was created. In this study we sought to characterize the development of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a control. Rats were examined at 34 weeks of age 12 weeks after the onset of hyperglycemia in ZDSD rats. At this time ZDSD rats were severely insulin resistant with slowing of both motor and sensory nerve conduction velocities. ZDSD rats also had fatty livers, elevated serum free fatty acids, triglycerides, and cholesterol, and elevated sciatic nerve nitrotyrosine levels. The corneas of ZDSD rats exhibited a decrease in subbasal epithelial corneal nerves and sensitivity. ZDSD rats were hypoalgesic but intraepidermal nerve fibers in the skin of the hindpaw were normal compared to Sprague-Dawley rats. However, the number of Langerhans cells was decreased. Vascular reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve, to acetylcholine and calcitonin gene-related peptide was impaired in ZDSD rats. These data indicate that ZDSD rats develop many of the neural complications associated with type 2 diabetes and are a good animal model for preclinical investigations of drug development for diabetic neuropathy.

Neurophysiological and morphological responses to treatment with acetyl-L-carnitine in a sciatic nerve injury model: preliminary data

2011 ◽  
Vol 37 (6) ◽  
pp. 529-536 ◽  
Author(s):  
S. Karsidag ◽  
A. Akcal ◽  
S. Sahin ◽  
S. Karsidag ◽  
F. Kabukcuoglu ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Motor Nerve ◽  
Sprague Dawley ◽  
Motor Nerve Conduction ◽  
Sprague Dawley Rats ◽  
Injury Model ◽  
Electrophysiological Measurements ◽  
And Control ◽  
Different Levels

We investigated the effects of acetyl-L-carnitine (ALCAR) on the recovery of sciatic nerve injuries in rats. Sprague Dawley rats were randomized to two groups: ALCAR treated (for 14 days) and control. Each group was divided into three subgroups: distal transection, proximal transection, and grafted. Distal latencies, amplitudes, and motor nerve conduction velocities were measured. In the third month, biopsies were taken and examined under light microscopy. Electrophysiological measurements demonstrated that regeneration occurred earlier and was better in the ALCAR group, particularly in the distal transection subgroup. Better results were obtained in the distal transection subgroup in terms of axonal regeneration compared with the proximal transection and grafted subgroups because the regenerating segment was shorter. ALCAR enhanced the quality of neural recovery at the different levels and in different types of repair, and led to a decline in nerve death.

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