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

2019 ◽  
Vol 2 (2) ◽  
pp. 72-79
Author(s):  
William C. Eward ◽  
Keithara Davis ◽  
Alison Putterman ◽  
Edward Morrison ◽  
David Ruch
Keyword(s):  
Vomeronasal Organ ◽  
Nerve Conduit ◽  
Defect Model ◽  
Functional Index ◽  
Segmental Nerve ◽  
Sciatic Functional Index

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.

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

Fate and contribution of induced pluripotent stem cell-derived neurospheres transplanted with nerve conduits to promoting peripheral nerve regeneration in mice

2021 ◽  
pp. 1-11
Author(s):  
Takuya Yokoi ◽  
Takuya Uemura ◽  
Kiyohito Takamatsu ◽  
Kosuke Shintani ◽  
Ema Onode ◽  
...  
Keyword(s):  
Stem Cell ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Pluripotent Stem Cell ◽  
Peripheral Nerve Regeneration ◽  
Induced Pluripotent Stem Cell ◽  
Nerve Conduit ◽  
Nerve Conduits ◽  
Induced Pluripotent

BACKGROUND: We previously demonstrated that a bioabsorbable nerve conduit coated with mouse induced pluripotent stem cell (iPSC)-derived neurospheres accelerated peripheral nerve regeneration in mice. OBJECTIVE: We examined the fate and utility of iPSC-derived neurospheres transplanted with nerve conduits for the treatment of sciatic nerve gaps in mice. METHODS: Complete 5 mm defects were created in sciatic nerves and reconstructed using nerve conduits that were either uncoated or coated with mouse iPSC-derived neurospheres. The survival of the neurospheres on the nerve conduits was tracked using an in vivo imaging. The localization of the transplanted cells and regenerating axons was examined histologically. The gene expression levels in the nerve conduits were evaluated. RESULTS: The neurospheres survived for at least 14 days, peaking at 4–7 days after implantation. The grafted neurospheres remained as Schwann-like cells within the nerve conduits and migrated into the regenerated axons. The expression levels of ATF3, BDNF, and GDNF in the nerve conduit coated with neurospheres were upregulated. CONCLUSIONS: Mouse iPSC-derived neurospheres transplanted with nerve conduits for the treatment of sciatic nerve defects in mice migrated into regenerating axons, survived as Schwann-like cells, and promoted axonal growth with an elevation in the expression of nerve regeneration-associated trophic factors.

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.

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

2014 ◽  
Vol 92 (12) ◽  
pp. 1013-1019 ◽  
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.

Influences of Repair Site Tension and Conduit Splinting on Peripheral Nerve Reconstruction

Hand ◽  
2020 ◽  
pp. 155894472097411
Author(s):  
David M. Brogan ◽  
Christopher J. Dy ◽  
Dana Rioux-Forker ◽  
Jason Wever ◽  
Fraser J. Leversedge
Keyword(s):  
Sciatic Nerve ◽  
Functional Outcomes ◽  
Primary Repair ◽  
Nerve Fibers ◽  
Reconstruction Method ◽  
Segmental Defect ◽  
Nerve Reconstruction ◽  
Defect Model ◽  
Repair Site ◽  
Significant Difference

Background We investigated the use of a conduit splinting technique to mitigate tension at the coaptation site of a rodent nerve defect model to determine the optimal reconstruction method for segmental nerve defects. Methods A rat sciatic nerve segmental defect model was created by excising 5mm of the sciatic nerve unilaterally. Four groups of 10 rats were each reconstructed using 1 of 4 techniques: primary repair, repair with conduit splinting, reverse isograft with conduit splinting, and reverse isograft without splinting. Functional outcomes were assessed at 6 weeks by measurement of Sciatic Functional Index (SFI), and sciatic nerves were harvested at the nonsurvival surgery. Histomorphologic measurements were reported as a value normalized to the average measurements of the control side. The primary outcomes were assessment of nerve continuity and the proportion of nerve fibers in the regenerating nerve compared with the uninjured side. Results The number of repair site rupture rates was lower when a conduit splint was used—less than half of the primary repairs under tension remained intact at 6 weeks. No difference was seen in axon number, size, and density between primary repairs and those augmented by conduit splints, but worse functional outcomes and more debris were present compared with the intact primary repairs. Conclusions Nerve conduit splinting reduced rupture rates, particularly for nerve repairs associated with a segmental defect. No significant difference was seen in the number of axons among techniques. Primary nerve repair under tension that did not rupture demonstrated superior SFI.

scholarly journals A Nerve Conduit Containing a Vascular Bundle and Implanted with Bone Marrow Stromal Cells and Decellularized Allogenic Nerve Matrix

2017 ◽  
Vol 26 (2) ◽  
pp. 215-228 ◽  
Author(s):  
Yukitoshi Kaizawa ◽  
Ryosuke Kakinoki ◽  
Ryosuke Ikeguchi ◽  
Soichi Ohta ◽  
Takashi Noguchi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Vascular Bundle ◽  
Dark Agouti ◽  
Nerve Conduit ◽  
Muscle Weight ◽  
Nerve Conduits ◽  
Nerve Model

Cells, scaffolds, growth factors, and vascularity are essential for nerve regeneration. Previously, we reported that the insertion of a vascular bundle and the implantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) into a nerve conduit promoted peripheral nerve regeneration. In this study, the efficacy of nerve conduits containing a vascular bundle, BM-MSCs, and thermally decellularized allogenic nerve matrix (DANM) was investigated using a rat sciatic nerve model with a 20-mm defect. Lewis rats were used as the sciatic nerve model and for the preparation of BM-MSCs, and Dark Agouti rats were used for the preparation of the DANM. The revascularization and the immunogenicity of the DANM were investigated histologically. The regeneration of nerves through nerve conduits containing vessels, BM-MSCs, and DANM (VBD group) was evaluated based on electrophysiological, morphometric, and reinnervated muscle weight measurements and compared with that of vessel-containing conduits that were implanted with BM-MSCs (VB group). The DANM that was implanted into vessel-containing tubes (VCTs) was revascularized by neovascular vessels that originated from the inserted vascular bundle 5–7 days after surgery. The number of CD8+ cells found in the DANM in the VCT was significantly smaller than that detected in the untreated allogenic nerve segment. The regenerated nerve in the VBD group was significantly superior to that in the VB group with regard to the amplitude of the compound muscle action potential detected in the pedal adductor muscle; the number, diameter, and myelin thickness of the myelinated axons; and the tibialis anterior muscle weight at 12 and 24 weeks. The additional implantation of the DANM into the BM-MSC-implanted VCT optimized the axonal regeneration through the conduit. Nerve conduits constructed with vascularity, cells, and scaffolds could be an effective strategy for the treatment of peripheral nerve injuries with significant segmental defects.

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