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

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.

Expression profiling of sciatic nerve in a Charcot-Marie-Tooth disease type 1a mouse model

2005 ◽  
Vol 79 (6) ◽  
pp. 825-835 ◽  
Author(s):  
Anneloor L.M.A. ten Asbroek ◽  
Camiel Verhamme ◽  
Marjon van Groenigen ◽  
Ruud Wolterman ◽  
Maryla M. de Kok-Nazaruk ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Mouse Model ◽  
Expression Profiling ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals Genetic variation in Charcot–Marie–Tooth genes contributes to sensitivity to paclitaxel-induced peripheral neuropathy

2020 ◽  
Vol 21 (12) ◽  
pp. 841-851
Author(s):  
Yongzhen Chen ◽  
Fang Fang ◽  
Kelley M Kidwell ◽  
Kiran Vangipuram ◽  
Lauren A Marcath ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Additive Model ◽  
Systemic Exposure ◽  
The Other ◽  
Hereditary Neuropathy ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Genetic Predictors ◽  
Paclitaxel Treatment ◽  
Tooth Disease

Aim: This study explored whether inherited variants in genes causing the hereditary neuropathy condition Charcot–Marie–Tooth disease are associated with sensitivity to paclitaxel-induced peripheral neuropathy (PN). Patients & methods: Hereditary neuropathy genes previously associated with risk of paclitaxel-induced PN were sequenced in paclitaxel-treated patients. Eight putative genetic predictors in five hereditary neuropathy genes ( ARHGEF10, SBF2, FGD4, FZD3 and NXN) were tested for association with PN sensitivity after accounting for systemic exposure and clinical variables. Results: FZD3 rs7833751, a proxy for rs7001034, decreased PN sensitivity (additive model, β = -0.41; 95% CI: -0.66 to -0.17; p = 0.0011). None of the other genetic predictors were associated with PN sensitivity. Conclusion: Our results support prior evidence that FZD3 rs7001034 is protective of PN and may be useful for individualizing paclitaxel treatment to prevent PN.

scholarly journals Association of the Charcot–Marie–Tooth disease gene ARHGEF10 with paclitaxel induced peripheral neuropathy in NCCTG N08CA (Alliance)

2015 ◽  
Vol 357 (1-2) ◽  
pp. 35-40 ◽  
Author(s):  
Ganesh K. Boora ◽  
Amit A. Kulkarni ◽  
Rahul Kanwar ◽  
Peter Beyerlein ◽  
Rui Qin ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Disease Gene ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals Intraepineurial Fat Quantification and Cross-sectional Area Analysis of the Sciatic Nerve Using MRI in Charcot-Marie-Tooth Disease Type 1A Patients

2021 ◽  
Author(s):  
Hyun Su Kim ◽  
Ji Hyun Lee ◽  
Young Cheol Yoon ◽  
Min Jae Cha ◽  
Soo Hyun Nam ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Disease Type ◽  
Sectional Area ◽  
Fat Quantification ◽  
Cross Sectional ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Level 3 ◽  
Level 1 ◽  
Tooth Disease

Abstract The objectives of this study were to assess the fat fraction (FF) and cross-sectional area (CSA) of the sciatic nerve in Charcot-Marie-Tooth disease type 1A (CMT1A) patients using Dixon-based proton density fat quantification MRI and to elucidate its potential association with clinical parameters. Thigh MRIs of 18 CMT1A patients and 18 age- and sex-matched volunteers enrolled for a previous study were reviewed. Analyses for FF and CSA of the sciatic nerve were performed at three levels (proximal to distal). CSA and FF were compared between the two groups and among the different levels within each group. The relationship between the MRI parameters and clinical data were assessed in the CMT1A patients. The CMT1A patients showed significantly higher FF at level 3 (p = 0.0217) and significantly larger CSA at all three levels compared with the control participants (p < 0.0001). Comparisons among levels showed significantly higher FF for levels 2 and 3 than for level 1 and significantly larger CSA for level 2 compared with level 1 in CMT1A patients. CSA at level 3 correlated positively with the CMT Neuropathy Score version 2 (CMTNSv2). In conclusion, the sciatic nerve FF of CMT1A patients was significantly higher on level 3 compared with both the controls and the measurements taken on more proximal levels, suggesting the possibility of increased intraepineurial fat within the sciatic nerves of CMT1A patients, with a possible distal tendency. Sciatic nerve CSA at level 3 correlated significantly and positively with CMTNSv2, suggesting its potential value as an imaging marker for clinical severity.

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

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).

scholarly journals Ndrg1-Deficient Mice Exhibit a Progressive Demyelinating Disorder of Peripheral Nerves

2004 ◽  
Vol 24 (9) ◽  
pp. 3949-3956 ◽  
Author(s):  
Tomohiko Okuda ◽  
Yujiro Higashi ◽  
Koichi Kokame ◽  
Chihiro Tanaka ◽  
Hisato Kondoh ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Schwann Cells ◽  
Peripheral Nerves ◽  
Sensory Neuropathy ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Hind Limbs ◽  
Deficient Mice ◽  
Tooth Disease

ABSTRACT NDRG1 is an intracellular protein that is induced under a number of stress and pathological conditions, and it is thought to be associated with cell growth and differentiation. Recently, human NDRG1 was identified as a gene responsible for hereditary motor and sensory neuropathy-Lom (classified as Charcot-Marie-Tooth disease type 4D), which is characterized by early-onset peripheral neuropathy, leading to severe disability in adulthood. In this study, we generated mice lacking Ndrg1 to analyze its function and elucidate the pathogenesis of Charcot-Marie-Tooth disease type 4D. Histological analysis showed that the sciatic nerve of Ndrg1-deficient mice degenerated with demyelination at about 5 weeks of age. However, myelination of Schwann cells in the sciatic nerve was normal for 2 weeks after birth. Ndrg1-deficient mice showed muscle weakness, especially in the hind limbs, but complicated motor skills were retained. In wild-type mice, NDRG1 was abundantly expressed in the cytoplasm of Schwann cells rather than the myelin sheath. These results indicate that NDRG1 deficiency leads to Schwann cell dysfunction, suggesting that NDRG1 is essential for maintenance of the myelin sheaths in peripheral nerves. These mice will be used for future analyses of the mechanisms of myelin maintenance.

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

2017 ◽  
Vol 23 (7) ◽  
pp. 7005-7008
Author(s):  
Ria Margiana ◽  
Saadatur R Pasaribu ◽  
Hamid Hasan Haikal
Keyword(s):  
Sciatic Nerve ◽  
Nerve Repair ◽  
Functional Index ◽  
Sciatic Functional Index ◽  
Additional Agent

scholarly journals Correlation between parameters of electrophysiological, histomorphometric and sciatic functional index evaluations after rat sciatic nerve repair

2006 ◽  
Vol 64 (3b) ◽  
pp. 750-756 ◽  
Author(s):  
Roberto Sergio Martins ◽  
Mario Gilberto Siqueira ◽  
Ciro Ferreira da Silva ◽  
José Píndaro Pereira Plese
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Fiber Diameter ◽  
Nerve Repair ◽  
Neural Regeneration ◽  
Poor Correlation ◽  
Functional Index ◽  
Rat Sciatic Nerve ◽  
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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