scholarly journals A new model of chronic peripheral nerve compression for basic research and pharmaceutical drug testing

2021 ◽  
Author(s):  
Lucas Degrugillier ◽  
Katharina M Prautsch ◽  
Dirk J Schaefer ◽  
Raphael Guzman ◽  
Stefan Schären ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Drug Testing ◽  
Basic Research ◽  
Nerve Compression ◽  
Sprague Dawley ◽  
Post Injury ◽  
New Therapeutic Approaches ◽  
Quantitative Measurements ◽  
Sprague Dawley Rats ◽  
Motor Outcomes

Aim: To develop a consistent model to standardize research in the field of chronic peripheral nerve neuropathy. Methods: The left sciatic nerve of 8-week-old Sprague–Dawley rats was compressed using a customized instrument leaving a defined post injury nerve lumen (400 μm, 250 μm, 100 μm, 0 μm) for 6 weeks. Sensory and motor outcomes were measured weekly, and histomorphology and electrophysiology after 6 weeks. Results: The findings demonstrated compression depth-dependent sensory and motor pathologies. Quantitative measurements revealed a significant myelin degeneration, axon irregularities and muscle atrophy. At the functional level, we highlighted the dynamics of the different injury profiles. Conclusion: Our novel model of chronic peripheral nerve compression is a useful tool for research on pathophysiology and new therapeutic approaches.

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.

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.

Therapeutic Effect of Vitamin D3 in a Rat Diffuse Axonal Injury Model

2005 ◽  
Vol 33 (1) ◽  
pp. 90-95 ◽  
Author(s):  
UA Malcok ◽  
G Sengul ◽  
HH Kadioglu ◽  
IH Aydin
Keyword(s):  
Vitamin D ◽  
Therapeutic Effect ◽  
Head Trauma ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Sprague Dawley ◽  
Post Injury ◽  
Sprague Dawley Rats ◽  
Injury Model ◽  
Impact Acceleration

We investigated the therapeutic effect of vitamin D3 in a rat diffuse axonal injury model. A total of 60 male Sprague-Dawley rats weighing 175 − 200 g were anaesthetized and subjected to head trauma using Marmarou's impact-acceleration model. The rats were then separated into two groups; one group was treated with vitamin D3 and the other with saline for up to 4 days after the head trauma. Rats from both groups were killed 1, 3 or 8 days post-injury. The brains were examined histopathologically and scored according to the level of neuronal, vascular and axonal damage. There were no significant differences between the groups after 1 or 3 days, but evaluation after 8 days revealed a significant improvement in the group treated with vitamin D3. Our data indicate that vitamin D3 has a beneficial effect in diffuse axonal injury and may be useful in the management of this condition.

Erythrocyte Coupled tPA Improves Outcomes of Percussion Brain Trauma in Rats.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 897-897 ◽  
Author(s):  
Kumkum Ganguly ◽  
Sherman C. Stein ◽  
Robert F. Groff ◽  
Jun Zhang ◽  
Douglas H. Smith ◽  
...  
Keyword(s):  
Lesion Size ◽  
Brain Trauma ◽  
Lesion Volume ◽  
Sprague Dawley ◽  
Post Injury ◽  
Fluid Percussion Injury ◽  
Sprague Dawley Rats ◽  
Post Traumatic ◽  
Traumatic Thrombosis ◽  
Lateral Fluid Percussion

Abstract Coupling tissue plasminogen activator (tPA) to carrier red blood cells (RBC): i) restricts tPA’s permeation into tissues and pre-existing hemostatic clots, minimizing hemorrhage; ii) protects it from plasma inhibitors; and iii) prolongs its circulation, permitting incorporation into nascent clots and their lysis from within. These features support the thromboprophylactic utility of RBC coupled tPA (RBC/tPA). In this study we explored the utility of RBC/tPA in traumatic brain injury (TBI), a disorder in which both cerebral thrombosis leading to cerebral ischemia and intracerebral hemorrhage (ICH) have been implicated. Eleven male, Sprague-Dawley rats (340–400g) were subjected to a moderate (avg. peak pressure 2.6atm) lateral fluid percussion injury to the left hemisphere. Rats were given a single intravenous dose of RBC/tPA (0.05mg/Kg, n=5) or vehicle (n=4), 15 min post-injury. Animals were sacrificed 48h later for histopathology and staining for fibrin. The lesions in control animals occupied 8.3 ± 2.8% (mean±SD) of the hemispheric volume. Animals treated with RBC/tPA had a significant decrease in mean lesion volume (1.4±0.7%; p<0.001). Thrombotic burden was reduced from a mean of 10 clots in vehicle-treated to 1 per RBC/tPA-treated rats p<0.001). These data indicate that RBC/tPA attenuates post-traumatic thrombosis without aggravating hemorrhage induced by TBI. These observations support the safety of RBC/tPA in thromboprophylaxis even in the context of brain trauma, due to intravascular containment of RBC/tPA, among other factors. Durable lysis of post-traumatic thrombi by long-circulating RBC/tPA may alleviate secondary brain ischemia and resultant ICH. Correlation between reduction of thrombotic burden and lesion size implicate thrombosis in the pathophysiology of parenchymal brain damage after head trauma. Supported by PENN Research Foundation, HL66442, HL60169 and in part by NS38104.

scholarly journals Qualitative and Quantitative Neuropathology Approaches Using Magnetic Resonance Microscopy (Diffusion Tensor Imaging) and Stereology in a Hexachlorophene Model of Myelinopathy in Sprague-Dawley Rats

2020 ◽  
Vol 48 (8) ◽  
pp. 965-980
Author(s):  
Robert C. Sills ◽  
G. Allan Johnson ◽  
Robert J. Anderson ◽  
Crystal L. Johnson ◽  
Michael Staup ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Magnetic Resonance ◽  
Diffusion Tensor ◽  
Magnetic Resonance Microscopy ◽  
Sprague Dawley ◽  
Qualitative And Quantitative ◽  
Quantitative Measurements ◽  
Sprague Dawley Rats ◽  
Intramyelinic Edema

It is well established that hexachlorophene, which is used as an antibacterial agent, causes intramyelinic edema in humans and animal models. The hexachlorophene myelinopathy model, in which male Sprague-Dawley rats received 25 to 30 mg/kg hexachlorophene by gavage for up to 5 days, provided an opportunity to compare traditional neuropathology evaluations with magnetic resonance microscopy (MRM) findings. In addition, stereology assessments of 3 neuroanatomical sites were compared to quantitative measurements of similar structures by MRM. There were positive correlations between hematoxylin and eosin and luxol fast blue stains and MRM for identifying intramyelinic edema in the cingulum of corpus callosum, optic chiasm, anterior commissure (aca), lateral olfactory tracts, pyramidal tracts (py), and white matter tracts in the cerebellum. Stereology assessments were focused on the aca, longitudinal fasciculus of the pons, and py and demonstrated differences between control and treated rats, as was observed using MRM. The added value of MRM assessments was the ability to acquire qualitative 3-dimensional (3-D) images and obtain quantitative measurements of intramyelinic edema in 26 neuroanatomical sites in the intact brain. Also, diffusion tensor imaging (fractional anisotropy [FA]) indicated that there were changes in the cytoarchitecture of the white matter as detected by decreases in the FA in the treated compared to the control rats. This study demonstrates creative strategies that are possible using qualitative and quantitative assessments of potential white matter neurotoxicants in nonclinical toxicity studies. Our results lead us to the conclusion that volumetric analysis by MRM and stereology adds significant value to the standard 2-D microscopic evaluations.

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 A composite neurobehavioral test to evaluate acute functional deficits after cerebellar haemorrhage in rats

2017 ◽  
Vol 38 (3) ◽  
pp. 433-446 ◽  
Author(s):  
Devin W McBride ◽  
Derek Nowrangi ◽  
Harpreet Kaur ◽  
Guangyong Wu ◽  
Lei Huang ◽  
...  
Keyword(s):  
Cost Effective ◽  
Sprague Dawley ◽  
Stroke Subtype ◽  
Post Injury ◽  
Cerebellar Haemorrhage ◽  
Functional Deficits ◽  
Sham Surgery ◽  
Sprague Dawley Rats ◽  
Cerebellar Injury ◽  
Injury Models

Cerebellar haemorrhage accounts for 5–10% of all intracerebral haemorrhages and leads to severe, long-lasting functional deficits. Currently, there is limited research on this stroke subtype, which may be due to the lack of a suitable composite neuroscoring system specific for cerebellar injury in rodents. The purpose of this study is to develop a comprehensive composite neuroscore test for cerebellar injury using a rat model of cerebellar haemorrhage. Sixty male Sprague-Dawley rats were subjected to either sham surgery or cerebellar haemorrhage. Twenty-four hours post-injury, neurological behaviour was evaluated using 17 cost-effective and easy-to-perform tests, and a composite neuroscore was developed. The composite neuroscore was then used to assess functional recovery over seven days after cerebellar haemorrhage. Differences in the composite neuroscore deficits for the mild and moderate cerebellar haemorrhage models were observed for up to five days post-ictus. Until now, a composite neuroscore for cerebellar injury was not available for rodent studies. Herein, using mild and moderate cerebellar haemorrhage rat models a composite neuroscore for cerebellar injury was developed and used to assess functional deficits after cerebellar haemorrhage. This composite neuroscore may also be useful for other cerebellar injury models.

scholarly journals Pyrogenic and neuroinflammatory properties of zymosan and its potential as an alternative to live yeast in antipyretic drug testing

FACETS ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. 162-182 ◽  
Author(s):  
Rachael Dangarembizi ◽  
Christoph D. Rummel ◽  
Joachim Roth ◽  
Kennedy H. Erlwanger ◽  
Michael T. Madziva ◽  
...  
Keyword(s):  
Drug Testing ◽  
Core Body Temperature ◽  
Subcutaneous Administration ◽  
Circumventricular Organs ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Cell Wall Extract ◽  
Inflammatory Drugs ◽  
Core Body

Zymosan, an immunogenic cell wall extract of Saccharomyces cerevisiae has potential for use as an experimental pyrogen. However, the short-lived sickness responses noted with intraperitoneal and intra-articular administration of zymosan limits investigations on the long-term effectiveness of antipyretic drugs. Thus, there remains a need to establish an alternative route of zymosan administration that could induce long-lived fevers and inflammation. We injected male Sprague Dawley rats (250–300 g) subcutaneously with zymosan (30 or 300 mg/kg) or saline; n = 7–8. We measured core body temperature, cage activity, food intake and body mass for 24 h after injection. Blood and brain samples were collected at 2, 8, and 18 h after injection. Zymosan (300 mg/kg) induced fever, lethargy, and anorexia, which lasted for 24 h. Zymosan-induced sickness responses were accompanied by increased blood plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α; activation of inflammatory transcription factors (nuclear factor (NF) for IL-6, signal transducer and activator of transcription (STAT)-3, and NF-κB) in the hypothalamus and circumventricular organs; and increased hypothalamic mRNA expression of TNF-α, IL-1β, and IL-6 and rate-limiting enzymes for prostaglandin synthesis. Our results confirm the suitability of subcutaneous administration of zymosan for screening antipyretic and anti-inflammatory drugs in rats.

Sign in / Sign up

Export Citation Format

Share Document