Comparison of Various Additional Agent on Sciatic Nerve Repair on Sciatic Functional Index

The rat sciatic nerve is a well-established model for the study of recovery from peripheral nerve injuries. Traditional methods of assessing nerve regeneration after nerve injury and repair, such as electrophysiology and histomorphometry, despite widely used in neural regeneration experiments, do not necessarily correlate with return of motor and sensory functions. The aim of this experimental study is to investigate the possible correlation between several parameters of peripheral nerve regeneration after repair of sectioned sciatic nerve in Wistar rat. A two-stage approach was used to obtain 17 parameters after electrophysiological, morphometric and sciatic functional index evaluations. Pearson's correlation analysis was performed between these results. Only two positives correlations between different classes of peripheral nerve assessments were noted, between sciatic functional index and proximal nerve fiber diameter (r=0.56, p<0.01) and between sciatic functional index and distal fiber diameter (r=0.50, p<0.01). The data presented in our study demonstrates that there is a poor correlation between the sciatic functional index and outcome measures of electrophysiological and morphometric evaluations.

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The effects of adipose-derived multipotent mesenchymal stromal cells transplantation on motor activity and function of the sciatic nerve in mice with peripheral neuropathy

Cell and Organ Transplantology ◽

10.22494/cot.v8i2.111 ◽

2020 ◽

Vol 8 (2) ◽

Author(s):

V. Rubtsov ◽

◽

I. Govbach ◽

A. Ustymenko ◽

V. Kyryk ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Sciatic Nerve ◽

Motor Activity ◽

Multipotent Mesenchymal Stromal Cells ◽

Beam Test ◽

Functional Index ◽

Balance Beam ◽

Charcot Marie Tooth Disease ◽

Sciatic Functional Index ◽

Tooth Disease

The Charcot–Marie–Tooth disease type 1A (SHMT1A) is one of the most common hereditary motor-sensory peripheral neuropathies, which is caused by demyelination of motor and sensory nerve fibers and leads to nerve dysfunction. There are currently no effective treatments for hereditary neuropathies, but recent studies indicate a number of potentially effective therapeutic agents, including multipotent mesenchymal stromal cells (MMSCs). The aim of the study was to evaluate the effect of adipose-derived MMSCc transplantation on motor activity and sciatic nerve function of transgenic mice with peripheral neuropathy. Materials and methods. The transgenic B6.Cg-Tg(PMP22)C3Fbas/J mice with peripheral neuropathy were injected intramuscularly with MMSCs, which were isolated from the adipose tissue of FVB-Cg-Tg(GFPU) mice transgenic by GFP. Motor activity of experimental animals was investigated in dynamics after 2, 4, 6, 8 and 10 weeks using the behavioral balance beam test. The functions of the sciatic nerve were analyzed according to the footprint test by calculating the sciatic functional index (SFI). Results. For 2-10 weeks in animals with neuropathy, disease progression was observed, which was expressed in an increasing increase in the number of slidings of the hind limbs from the beam and the time required to walking the distance. SFI in animals of this group decreased and at the 10th week was -47.0 ± 2 units. In contrast, from the 2nd week of the experiment, mice with neuropathy after MMSCs transplantation performed 20 % fewer slidings and spent 11 % less time in the balance beam test compared to animals without cell transplantation. In the same period, an increase of SFI up to -30.2 ± 2 versus -34.6 ± 0.9 units was observed, respectively. At the 10th week after the injection of MMSC, the SFI value was -10.1 ± 2.3 units and correlated with a decrease in the number of slidings and the time spent on the balance beam test. Conclusions. MMSCs transplantation improves the sciatic functional index and fine motor skills in mice with peripheral neuropathy. MMSCs have the potential to be an effective therapeutic agent in the treatment of peripheral neuropathy at Charcot-Marie-Tooth disease.

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Functional evaluation outcomes correlate with histomorphometric changes in the rat sciatic nerve crush injury model: A comparison between sciatic functional index and kinematic analysis

PLoS ONE ◽

10.1371/journal.pone.0208985 ◽

2018 ◽

Vol 13 (12) ◽

pp. e0208985 ◽

Cited By ~ 5

Author(s):

Tianshu Wang ◽

Akira Ito ◽

Tomoki Aoyama ◽

Ryo Nakahara ◽

Akihiro Nakahata ◽

...

Keyword(s):

Sciatic Nerve ◽

Kinematic Analysis ◽

Crush Injury ◽

Sciatic Nerve Crush ◽

Functional Evaluation ◽

Functional Index ◽

Nerve Crush ◽

Injury Model ◽

Sciatic Functional Index ◽

Nerve Crush Injury

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Nerve Conduit Enhancement with Vomeronasal Organ Improves Rat Sciatic Functional Index in a Segmental Nerve Defect Model

The Duke Orthopaedic Journal ◽

10.5005/jp-journals-10017-1002 ◽

2011 ◽

Vol 1 (1) ◽

pp. 9-15

Author(s):

William C Eward ◽

Carter Lipton ◽

Jonathan Barnwell ◽

Thomas L Smith ◽

Matthew Crowe ◽

...

Keyword(s):

Sciatic Nerve ◽

Vomeronasal Organ ◽

Nerve Conduit ◽

Segmental Defect ◽

Defect Model ◽

Functional Index ◽

Axon Density ◽

Nerve Conduits ◽

Segmental Nerve ◽

Sciatic Functional Index

ABSTRACT Background Segmental nerve loss presents a challenge to the reconstructive surgeon. The best regenerative results are obtained by using autologous interpositional nerve grafts. While this method can be successful, it necessitates a second surgical step, sacrifices donor nerve function and depends upon a finite supply of potential donor nerves. Collagen nerve conduits are commercially available for reconstruction of segmental nerve defects. However, no conduit-based reconstructive strategy has been as successful as autograft reconstruction. We hypothesized that collagen nerve conduits used to bridge a sciatic nerve defect may be enhanced by grafting with vomeronasal organ (VNO), owing to the unique capacity for regeneration of this mammalian olfactory tissue. Methods 21 rats underwent resection of a 1.0 cm segment of sciatic nerve. Seven rats underwent repair of the resultant nerve defect using a commercially available collagen nerve conduit (NeuraGen, Integra Life Sciences, Plainsboro NJ, USA). Seven rats underwent immediate repair of the nerve defect using the conduit filled with freshly harvested VNO allograft. An additional Seven rats underwent resection of a 4 mm segment of sciatic nerve and direct epineural repair. At 14 weeks postoperatively, all animals underwent walking track analysis. Toe prints were analyzed morphometrically to permit calculation of sciatic functional index (SFI). At 16 weeks postoperatively, rats were sacrificed and tissues were processed for histomorphometric analysis. This analysis included quantification of the number and diameter of myelinated axons as well as calculation of the axon density. Results All animals survived treatment without any serious surgical complications. All sciatic nerves were in continuity at sacrifice. All animals showed signs of sciatic denervation (decubitus ulcers, muscle atrophy) postoperatively. At 14 weeks, the mean sciatic functional index (SFI) was significantly higher in the VNO-enhanced group (p = 0.006) and the epineural repair (ER) groups (p = 0.004) than the conduit-only (CO) group. SFI was equivalent between VNO and ER groups (p = 0.338). Axon density was greater in the VNO (p = 0.013) and ER groups (p = 0.048) than in the CO group. Axon density was equivalent between the VNO and ER groups (p = 0.306). Conclusions In a rat sciatic nerve segmental defect model, modification of collagen nerve conduits to contain the pluripotent neuroepitheilial tissue vomeronasal organ (VNO) improves functional recovery and offers increased axon density relative to reconstruction with an empty conduit (CO).

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Effect of aminoguanidine on sciatic functional index, oxidative stress, and rate of apoptosis in an experimental rat model of ischemia–reperfusion injury

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2014-0315 ◽

2014 ◽

Vol 92 (12) ◽

pp. 1013-1019 ◽

Cited By ~ 4

Author(s):

Alipour Mohsen ◽

Ghadiri Soufi Farhad ◽

Jafari Mohammad-Reza

Keyword(s):

Oxidative Stress ◽

Sciatic Nerve ◽

Reperfusion Injury ◽

Rat Model ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Protective Effects ◽

Functional Index ◽

Positive Effects ◽

Sciatic Functional Index

This study was conducted to investigate the potential protective effects of aminoguanidine (AG) on sciatic functional index (SFI), oxidative stress status, and apoptosis index using a rat model of experimental sciatic nerve ischemia–reperfusion injury (I/R). Treatment groups received 150 mg AG/kg body mass, 24 h after the induction of ischemia. After reperfusion for 2, 4, 7, 14, and 28 days, we evaluated measured SFI, plasma antioxidant enzymes, total antioxidant capacity (TAC), malondialdehyde (MDA), and index of apoptosis. SFI was significantly improved on the 7th and 14th day of reperfusion in the AG-treated groups. AG treatment resulted in the significant reduction of MDA levels on the 7th and 14th day of reperfusion. TAC was only increased after 7 days of reperfusion compared with the untreated group. SOD activity was decreased in both the untreated and AG-treated groups by comparison with the control, but did not show a significant change. GPx activity decreased only after 7 days of reperfusion. The maximal rate of apoptosis occurred on the 7th day of reperfusion. Treatment with AG significantly reduced this enhancement. AG exhibits positive effects against sciatic nerve I/R injury, possibly in part because of the protective effects of AG against apoptosis and I/R-induced oxidative stress.

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Closing the Gap Between Mammalian and Invertebrate Peripheral Nerve Injury: Protocol for a Novel Nerve Repair

JMIR Research Protocols ◽

10.2196/18706 ◽

2020 ◽

Vol 9 (8) ◽

pp. e18706

Author(s):

Maxwell Vest ◽

Addison Guida ◽

Cory Colombini ◽

Kristina Cordes ◽

Diana Pena ◽

...

Keyword(s):

Peripheral Nerve ◽

Peripheral Nerve Injury ◽

Action Potentials ◽

Morphological Analysis ◽

Nerve Repair ◽

Distal Segment ◽

Negative Control ◽

Functional Index ◽

Behavioral Recovery ◽

Sciatic Functional Index

Background Outcomes after peripheral nerve injuries are poor despite current nerve repair techniques. Currently, there is no conclusive evidence that mammalian axons are capable of spontaneous fusion after transection. Notably, certain invertebrate species are able to auto-fuse after transection. Although mammalian axonal auto-fusion has not been observed experimentally, no mammalian study to date has demonstrated regenerating axolemmal membranes contacting intact distal segment axolemmal membranes to determine whether mammalian peripheral nerve axons have the intrinsic mechanisms necessary to auto-fuse after transection. Objective This study aims to assess fusion competence between regenerating axons and intact distal segment axons by enhancing axon regeneration, delaying Wallerian degeneration, limiting the immune response, and preventing myelin obstruction. Methods This study will use a rat sciatic nerve model to evaluate the effects of a novel peripheral nerve repair protocol on behavioral, electrophysiologic, and morphologic parameters. This protocol consists of a variety of preoperative, intraoperative, and postoperative interventions. Fusion will be assessed with electrophysiological conduction of action potentials across the repaired transection site. Axon-axon contact will be assessed with transmission electron microscopy. Behavioral recovery will be analyzed with the sciatic functional index. A total of 36 rats will be used for this study. The experimental group will use 24 rats and the negative control group will use 12 rats. For both the experimental and negative control groups, there will be both a behavior group and another group that will undergo electrophysiological and morphological analysis. The primary end point will be the presence or absence of action potentials across the lesion site. Secondary end points will include behavioral recovery with the sciatic functional index and morphological analysis of axon-axon contact between regenerating axons and intact distal segment axons. Results The author is in the process of grant funding and institutional review board approval as of March 2020. The final follow-up will be completed by December 2021. Conclusions In this study, the efficacy of the proposed novel peripheral nerve repair protocol will be evaluated using behavioral and electrophysiologic parameters. The author believes this study will provide information regarding whether spontaneous axon fusion is possible in mammals under the proper conditions. This information could potentially be translated to clinical trials if successful to improve outcomes after peripheral nerve injury. International Registered Report Identifier (IRRID) PRR1-10.2196/18706

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Closing the Gap Between Mammalian and Invertebrate Peripheral Nerve Injury: Protocol for a Novel Nerve Repair (Preprint)

10.2196/preprints.18706 ◽

2020 ◽

Author(s):

Maxwell Vest ◽

Addison Guida ◽

Cory Colombini ◽

Kristina Cordes ◽

Diana Pena ◽

...

Keyword(s):

Peripheral Nerve ◽

Peripheral Nerve Injury ◽

Action Potentials ◽

Morphological Analysis ◽

Nerve Repair ◽

Distal Segment ◽

Negative Control ◽

Functional Index ◽

Behavioral Recovery ◽

Sciatic Functional Index

BACKGROUND Outcomes after peripheral nerve injuries are poor despite current nerve repair techniques. Currently, there is no conclusive evidence that mammalian axons are capable of spontaneous fusion after transection. Notably, certain invertebrate species are able to auto-fuse after transection. Although mammalian axonal auto-fusion has not been observed experimentally, no mammalian study to date has demonstrated regenerating axolemmal membranes contacting intact distal segment axolemmal membranes to determine whether mammalian peripheral nerve axons have the intrinsic mechanisms necessary to auto-fuse after transection. OBJECTIVE This study aims to assess fusion competence between regenerating axons and intact distal segment axons by enhancing axon regeneration, delaying Wallerian degeneration, limiting the immune response, and preventing myelin obstruction. METHODS This study will use a rat sciatic nerve model to evaluate the effects of a novel peripheral nerve repair protocol on behavioral, electrophysiologic, and morphologic parameters. This protocol consists of a variety of preoperative, intraoperative, and postoperative interventions. Fusion will be assessed with electrophysiological conduction of action potentials across the repaired transection site. Axon-axon contact will be assessed with transmission electron microscopy. Behavioral recovery will be analyzed with the sciatic functional index. A total of 36 rats will be used for this study. The experimental group will use 24 rats and the negative control group will use 12 rats. For both the experimental and negative control groups, there will be both a behavior group and another group that will undergo electrophysiological and morphological analysis. The primary end point will be the presence or absence of action potentials across the lesion site. Secondary end points will include behavioral recovery with the sciatic functional index and morphological analysis of axon-axon contact between regenerating axons and intact distal segment axons. RESULTS The author is in the process of grant funding and institutional review board approval as of March 2020. The final follow-up will be completed by December 2021. CONCLUSIONS In this study, the efficacy of the proposed novel peripheral nerve repair protocol will be evaluated using behavioral and electrophysiologic parameters. The author believes this study will provide information regarding whether spontaneous axon fusion is possible in mammals under the proper conditions. This information could potentially be translated to clinical trials if successful to improve outcomes after peripheral nerve injury. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/18706

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IL-17F depletion accelerates chitosan conduit guided peripheral nerve regeneration

Acta Neuropathologica Communications ◽

10.1186/s40478-021-01227-1 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Feixiang Chen ◽

Weihuang Liu ◽

Qiang Zhang ◽

Ping Wu ◽

Ao Xiao ◽

...

Keyword(s):

Bone Marrow ◽

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Knockout Mice ◽

Inflammatory Markers ◽

Nerve Repair ◽

Peripheral Nerve Regeneration ◽

Wild Type ◽

Anti Inflammatory

AbstractPeripheral nerve injury is a serious health problem and repairing long nerve deficits remains a clinical challenge nowadays. Nerve guidance conduit (NGC) serves as the most promising alternative therapy strategy to autografts but its repairing efficiency needs improvement. In this study, we investigated whether modulating the immune microenvironment by Interleukin-17F (IL-17F) could promote NGC mediated peripheral nerve repair. Chitosan conduits were used to bridge sciatic nerve defect in IL-17F knockout mice and wild-type mice with autografts as controls. Our data revealed that IL-17F knockout mice had improved functional recovery and axonal regeneration of sciatic nerve bridged by chitosan conduits comparing to the wild-type mice. Notably, IL-17F knockout mice had enhanced anti-inflammatory macrophages in the NGC repairing microenvironment. In vitro data revealed that IL-17F knockout peritoneal and bone marrow derived macrophages had increased anti-inflammatory markers after treatment with the extracts from chitosan conduits, while higher pro-inflammatory markers were detected in the Raw264.7 macrophage cell line, wild-type peritoneal and bone marrow derived macrophages after the same treatment. The biased anti-inflammatory phenotype of macrophages by IL-17F knockout probably contributed to the improved chitosan conduit guided sciatic nerve regeneration. Additionally, IL-17F could enhance pro-inflammatory factors production in Raw264.7 cells and wild-type peritoneal macrophages. Altogether, IL-17F may partially mediate chitosan conduit induced pro-inflammatory polarization of macrophages during nerve repair. These results not only revealed a role of IL-17F in macrophage function, but also provided a unique and promising target, IL-17F, to modulate the microenvironment and enhance the peripheral nerve regeneration.

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