An Evaluation of Different Methods of Peripheral Nerve Repair In Normal and Diabetic Rats

1997 ◽  
Vol 22 (4) ◽  
pp. 486-491 ◽  
Author(s):  
A. C. FULLARTON ◽  
M. A. GLASBY
Keyword(s):  
Nerve Regeneration ◽  
Nerve Injury ◽  
Type I Diabetes ◽  
Nerve Repair ◽  
Fibre Diameter ◽  
Diabetic Rats ◽  
Type I ◽  
Nerve Crush ◽  
Nerve Autograft ◽  
Type Of Injury

Successful nerve regeneration depends on the type of injury, the method of repair and the metabolic status of the animal. A state similar to poorly controlled Type I diabetes mellitus in man was induced and maintained in rats using streptozotocin. This provided a model for the study of nerve regeneration in diabetes over a period of 150 days. Two methods of nerve injury (crush and transection) and three methods of repair (epineurial suture, nerve autograft and freeze-thawed skeletal muscle autograft) were compared using electrophysiological and histological methods. The diabetic state did not affect the degree of recovery of nerve conduction velocity after nerve injury. By 150 days, recovery to control values of axon and nerve fibre diameters was not attained. Recovery of axon and fibre diameter was significantly poorer in the diabetic nerve crush group compared with the non-diabetic nerve crush group. It is concluded that this was because of poorer regeneration in diabetic nerve.

scholarly journals Recent Findings on the Effects of Pharmacological Agents on the Nerve Regeneration after Peripheral Nerve Injury

2020 ◽  
Vol 18 (11) ◽  
pp. 1154-1163
Author(s):  
Samira Bolandghamat ◽  
Morteza Behnam-Rassouli
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Molecular Mechanisms ◽  
Functional Disability ◽  
Nerve Repair ◽  
Invasive Treatment ◽  
Pharmacological Agents ◽  
Non Invasive ◽  
Repair Techniques

: Peripheral nerve injuries (PNIs) are accompanied with neuropathic pain and functional disability. Despite improvements in surgical repair techniques in recent years, the functional recovery is yet unsatisfied. Indeed a successful nerve repair depends not only on the surgical strategy but also on the cellular and molecular mechanisms involved in traumatic nerve injury. In contrast to all strategies suggested for nerve repair, pharmacotherapy is a cheap, accessible and non-invasive treatment that can be used immediately after nerve injury. This study aimed to review the effects of some pharmacological agents on the nerve regeneration after traumatic PNI evaluated by functional, histological and electrophysiological assessments. In addition, some cellular and molecular mechanisms responsible for their therapeutic actions, restricted to neural tissue, are suggested. These findings can not only help to find better strategies for peripheral nerve repair, but also to identify the neuropathic effects of various medications and their mechanisms of action.

Reduced renal dopamine D1 receptor function in streptozotocin-induced diabetic rats

2004 ◽  
Vol 286 (3) ◽  
pp. F451-F457 ◽  
Author(s):  
Aditi Marwaha ◽  
Anees Ahmad Banday ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Atpase Activity ◽  
Sodium Excretion ◽  
Type I Diabetes ◽  
Receptor Activation ◽  
Diabetic Rats ◽  
D1 Receptor ◽  
Skf 38393 ◽  
Receptor Expression ◽  
Type I ◽  
Renal Dopamine

Dopamine, via activation of renal D1 receptors, inhibits the activities of Na-K-ATPase and Na/H exchanger and subsequently increases sodium excretion. Decreased renal dopamine production and sodium excretion are associated with type I diabetes. However, it is not known whether the response to D1 receptor activation is altered in type I diabetes. The present study was designed to examine the effect of streptozotocin-induced type I diabetes on renal D1 receptor expression and function. Streptozotocin treatment of Sprague-Dawley rats caused a fourfold increase in plasma levels of glucose along with a significant decrease in insulin levels compared with control rats. Intravenous administration of SKF-38393, a D1 receptor agonist, caused a threefold increase in sodium excretion in control rats. However, SKF-38393 failed to produce natriuresis in diabetic rats. SKF-38393 caused a concentration-dependent inhibition of Na-K-ATPase activity in renal proximal tubules of control rats. However, the ability of SKF-38393 to inhibit Na-K-ATPase activity was markedly diminished in diabetic rats. D1 receptor numbers and protein abundance as determined by [3H]SCH-23390 ligand binding and Western blot analysis were markedly reduced in diabetic rats compared with control rats. Moreover, SKF-38393 failed to stimulate GTPγS binding in proximal tubular membranes from diabetic rats compared with control rats. We conclude that the natriuretic response to D1 receptor activation is reduced in type I diabetes as a result of a decrease in D1 receptor expression and defective receptor G protein coupling. These abnormalities may contribute to the sodium retention associated with type I diabetes.

scholarly journals Therapeutic Effect of Exendin-4, a Long-Acting Analogue of Glucagon-Like Peptide-1 Receptor Agonist, on Nerve Regeneration after the Crush Nerve Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Koji Yamamoto ◽  
Masatoshi Amako ◽  
Yoritsuna Yamamoto ◽  
Toyokazu Tsuchihara ◽  
Hitoshi Nukada ◽  
...  
Keyword(s):  
Nerve Regeneration ◽  
Nerve Injury ◽  
Receptor Agonist ◽  
Tibialis Anterior Muscle ◽  
Sciatic Nerve Crush ◽  
Nerve Crush ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

Glucagon-like peptide-1 (GLP-1) is glucose-dependent insulinotropic hormone secreted from enteroendocrine L cells. Its long-acting analogue, exendin-4, is equipotent to GLP-1 and is used to treat type 2 diabetes mellitus. In addition, exendin-4 has effects on the central and peripheral nervous system. In this study, we administered repeated intraperitoneal (i.p.) injections of exendin-4 to examine whether exendin-4 is able to facilitate the recovery after the crush nerve injury. Exendin-4 injection was started immediately after crush injury and was repeated every day for subsequent 14 days. Rats subjected to sciatic nerve crush exhibited marked functional loss, electrophysiological dysfunction, and atrophy of the tibialis anterior muscle (TA). All these changes, except for the atrophy of TA, were improved significantly by the administration of exendin-4. Functional, electrophysiological, and morphological parameters indicated significant enhancement of nerve regeneration 4 weeks after nerve crush. These results suggest that exendin-4 is feasible for clinical application to treat peripheral nerve injury.

The Protective Effects of Lupine (Lupinus albus) Fruit Extract Against to Destructive Effects of Hyperglycemia in Type I Diabetic Rats

2020 ◽  
Vol 20 ◽  
Author(s):  
Sevinç Aydın ◽  
Tubay Kaya ◽  
Orhan Erman ◽  
Ökkeş Yılmaz
Keyword(s):  
Lipid Peroxidation ◽  
Total Protein ◽  
Type I Diabetes ◽  
Lupinus Albus ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Type I ◽  
Protective Effects ◽  
Fruit Extract

Backround: Lupinus albus is a member of Fabaceae family. As a natural or cultivated plant, Lupinus albus is distributed in Europe, Balkans and Turkey, especially in Marmara and Aegean regions. The lupine is a nutritious and protective plant against diabetes. Objective: In the present study, the effects of Lupinus albus fruits on malondialdehyde (MDA), reduced glutathione (GSH), total protein, ADEK vitamins, and cholesterol values, which are the indicators of oxidative damage and antioxidant defense. In this regard, muscle, liver, renal, and brain tissues of STZ-induced type I diabetes rats were studied. Methods: The analyzes of ADEK vitamins and cholesterol levels in tissues were performed via Shimadzu HPLC device. The lipid peroxidation levels were measured at 532 nm in spectrophotometer. Determination of GSH was read at 412 nm against blank, and for the total protein levels Lowry method was applied. Results: According to the results obtained, it was determined that, among the rats with induced type I diabetes, the group applied lupine fruit extract was found to have increased GSH level and decreased MDA levels in all the tissues. The protein values were increased in liver tissues but decreased in the other tissues. The level of vitamins were significantly increased in almost all the tissues in diabetic group. Conclusion: In the present study, it was shown that the lupine reduced the devastating effects of type I diabetes by decreasing the fasting blood glucose and lipid peroxidation values and increasing the glutathione level in comparison to the diabetic group.

Abstract 412: The Sodium-Glucose Cotransporter 2 Inhibitor Empagliflozin Improves Diabetic Complications in the Streptozotocin Type 1 Diabetes Mellitus Model by Interfering With Glucotoxicity and Rescue of Beta-Cell Function

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Philipp Welschof ◽  
Matthias Oelze ◽  
Swenja Kröller-Schön ◽  
Thomas Jansen ◽  
Michael Hausding ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Type I Diabetes ◽  
Cardiovascular Complications ◽  
Diabetic Rats ◽  
Low Grade ◽  
Type I ◽  
Urinary Glucose ◽  
And Oxidative Stress

Objectives: In diabetes, cardiovascular complications are associated with endothelial dysfunction and oxidative stress. Empagliflozin (Empa), as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i) in clinical development, offers a promising novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with Empa could improve endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated oxidative stress. Research Design and Methods: Type I diabetes in Wistar rats was induced by an intravenous injection of streptozotocin (60 mg/kg). One week after injection Empa was administered via drinking water for 7 weeks. Results: Treatment with Empa (10 and 30 mg/kg/d), showed reduction of blood glucose and a normalization of endothelial dysfunction (aortic rings) in diabetic rats and a reduced oxidative stress in aortic vessels (dihydroethidine staining) and in blood (phorbol ester/zymosan A-stimulated chemiluminescence). Additionally, the pro-inflammatory phenotype and glucotoxicity in diabetic animals was normalized by SGLT2i therapy. Conclusion: In this study we could demonstrate that Empa improves hyperglycemia and prevents the development of endothelial dysfunction and oxidative stress in type 1 diabetic rats. Future studies will investigate the underlying mechanisms of these antioxidant and anti-inflammatory effects with special emphasis on low-grade inflammation, glucotoxicity and oxidative stress, all of which contributes to cardiovascular complications.

Type I diabetes suppresses intracellular calcium ion increase normally evoked by heat stress in rat skeletal muscle

2021 ◽  
Author(s):  
Ryo Ikegami ◽  
Hiroaki Eshima ◽  
Toshiaki Nakajima ◽  
Shigeru Toyoda ◽  
David C. Poole ◽  
...  
Keyword(s):  
Heat Stress ◽  
Protein Expression ◽  
Type I Diabetes ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Type I ◽  
Male Wistar Rats ◽  
Intracellular Calcium Ion ◽  
And Function

Heat stress, via its effects on muscle intracellular Ca2+ concentrations ([Ca2+]i), has been invoked as a putative therapeutic countermeasure to Type 1 diabetes-induced muscle atrophy. Using in vivo muscle preparation we tested the hypothesis that impaired muscle Ca2+ homeostasis in type I diabetic rats is due to attenuated heat stress tolerance mediated via TRPV1. Male Wistar rats were assigned to 1 of 4 groups: 1.control 30oC (CONT 30oC), 2.CONT 40oC, 3.diabetes 30oC (DIA 30oC), 4.DIA 40oC. 40oC was selected because it just exceeds the TRPV1 activation threshold. Spinotrapezius muscles were exteriorized in vivo and loaded with the fluorescent Ca2+ probe Fura-2AM. [Ca2+]i was estimated over 20min using fluorescence microscopy in quiescent muscle held at the required temperature using calibrated heat source applied to the ventral muscle surface. Western blotting was performed to determine the protein expression levels of TRPV1 in spinotrapezius muscle. After 20min of heat stress, the CONT 40oC condition induced a 12.3% [Ca2+]i elevation that was absent from the DIA 40oC or other conditions. Thus, no significant differences were found among DIA 40oC, DIA 30oC and CONT 30oC. TRPV1 protein expression was decreased by 42.0% in DIA compared with CONT (P<0.05) and, unlike CONT, heat stress did not increase TRPV1 phosphorylation. In conclusion, diabetes suppresses TRPV1 protein expression and function and inhibits the elevated myocyte [Ca2+]i evoked normally by heat stress. These results suggest that capsaicin or other therapeutic strategies to increase Ca2+ accumulation via TRPV1 might be more effective than hyperthermic therapy for Type I diabetic patients.

scholarly journals Mesenchymal Stem Cell Treatment Perspectives in Peripheral Nerve Regeneration: Systematic Review

2021 ◽  
Vol 22 (2) ◽  
pp. 572
Author(s):  
Andrea Lavorato ◽  
Stefania Raimondo ◽  
Marina Boido ◽  
Luisa Muratori ◽  
Giorgia Durante ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
High Survival ◽  
Nerve Lesion ◽  
Differentiation Potential

Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations in movement and sensitivity. Spontaneous peripheral nerve recovery is often inadequate. In this context, nowadays, cell therapy represents one of the most innovative approaches in the field of nerve repair therapies. The purpose of this systematic review is to discuss the features of different types of mesenchymal stem cells (MSCs) relevant for peripheral nerve regeneration after nerve injury. The published literature was reviewed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A combination of the keywords “nerve regeneration”, “stem cells”, “peripheral nerve injury”, “rat”, and “human” were used. Additionally, a “MeSH” research was performed in PubMed using the terms “stem cells” and “nerve regeneration”. The characteristics of the most widely used MSCs, their paracrine potential, targeted stimulation, and differentiation potentials into Schwann-like and neuronal-like cells are described in this paper. Considering their ability to support and stimulate axonal growth, their remarkable paracrine activity, their presumed differentiation potential, their extremely low immunogenicity, and their high survival rate after transplantation, ADSCs appear to be the most suitable and promising MSCs for the recovery of peripheral nerve lesion. Clinical considerations are finally reported.

scholarly journals A Porcine Model of Peripheral Nerve Injury Enabling Ultra-Long Regenerative Distances: Surgical Approach, Recovery Kinetics, and Clinical Relevance

2019 ◽  
Author(s):  
Justin C. Burrell ◽  
Kevin D. Browne ◽  
John L. Dutton ◽  
Suradip Das ◽  
Daniel P. Brown ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Surgical Approach ◽  
Peripheral Nerve Injury ◽  
Peroneal Nerve ◽  
Porcine Model ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Common Peroneal Nerve ◽  
Nerve Autograft

AbstractApproximately 20 million Americans currently experience residual deficits from traumatic peripheral nerve injury. Despite recent advancements in surgical technique, peripheral nerve repair typically results in poor functional outcomes due to prolonged periods of denervation resulting from long regenerative distances coupled with relatively slow rates of axonal regeneration. Development of novel surgical solutions requires valid preclinical models that adequately replicate the key challenges of clinical peripheral nerve injury. Our team has developed a porcine model using Yucatan minipigs that provides an opportunity to investigate peripheral nerve regeneration using different nerves tailored for a specific mechanism of interest, such as (1) nerve modality: motor, sensory, and mixed-modality; (2) injury length: short versus long gap; and (3) total regenerative distance: proximal versus distal injury. Here, we describe a comprehensive porcine model of two challenging clinically relevant procedures for repair of long segmental lesions (≥ 5 cm) – the deep peroneal nerve repaired using a sural nerve autograft and the common peroneal nerve repaired using a saphenous nerve autograft – each featuring ultra-long total regenerative distances (up to 20 cm and 27 cm, respectively) to reach distal targets. This paper includes a detailed characterization of the relevant anatomy, surgical approach/technique, functional/electrophysiological outcomes, and nerve morphometry for baseline and autograft repaired nerves. These porcine models of major peripheral nerve injury are suitable as preclinical, translatable models for evaluating the efficacy, safety, and tolerability of next-generation artificial nerve grafts prior to clinical deployment.

scholarly journals Characteristics of cytokines in the sciatic nerve stumps and DRGs after rat sciatic nerve crush injury

2020 ◽  
Author(s):  
Ruirui Zhang ◽  
Sailing Chen ◽  
Zhangchun Cheng ◽  
Yinying Shen ◽  
Sheng Yi ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Immune Responses ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Nerve Repair ◽  
Expression Patterns ◽  
Crush Injury ◽  
Differentially Expressed ◽  
Sequencing Data ◽  
Nerve Crush

Abstract Background: Cytokines are essential cellular modulators of a variety of physiological and pathological activities, including peripheral nerve repair and regeneration. However, the molecular changes of these cellular mediators after peripheral nerve injury are not well clarified. The study is aimed to discover critical cytokines for the regenerative process of injured peripheral nerves.Methods: The sequencing data of the injured nerve stumps and the dorsal root ganglia (DRGs) of Sprague-Dawley (SD) rats subjected to sciatic nerve (SN) crush injury were analyzed to determine expression patterns of genes coding for cytokines. PCR experiments were used to validate the accuracy of sequencing data.Results: A total of 46, 52, and 54 upstream cytokines were differentially expressed in SNs at 1 day, 4 days, and 7 days after nerve injury. And a total of 25, 28, and 34 upstream cytokines were differentially expressed in DRGs at these time points. The expression patterns of some essential upstream cytokines were displayed in a heatmap and validated by PCR experiment. Bioinformatic analysis of these differentially expressed upstream cytokines after nerve injury demonstrated that inflammatory and immune responses were significantly involved.Conclusions: In summary, these findings provided an overview of the dynamic changes of cytokines in SNs and DRGs at different time points after rat nerve crush injury, elucidated the biological processes of differentially expressed cytokines, especially the important roles in inflammatory and immune responses after peripheral nerve injury, and thus might contribute to identification of potential treatments for peripheral nerve repair and regeneration.

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