Influence of Tacrolimus (FK506) on Nerve Regeneration Using Allografts: A Rat Sciatic Nerve Model

Shahraki, Mohammad Reza; Mohammadi, Rahim; Najafpour, Alireza

doi:10.1016/j.joms.2015.03.032

Cited by 27 publications

(31 citation statements)

References 27 publications

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“…Earlier axon regeneration in allografts with FK506 compared to allografts without FK506 was demonstrated experimentally [96]. Systemic application of tacrolimus at doses of 0.6 mg/kg found the amount of myelin debris in autologous nerve grafts to be decreasing [97].…”

Section: Tacrolimusmentioning

confidence: 99%

“…Shahraki et al demonstrated earlier axon regeneration in allografts with FK506 compared to allografts without FK506 (P < 0.05) [96]. Yan et al found that short treatment courses of 10 and 20 days with FK506 (in the graft model) were sufficient to reduce functional recovery time by 15 and 21%, respectively, compared with negative controls assessed by walking track analysis [90].…”

Section: Mechanisms Of Action Referencesmentioning

confidence: 99%

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The Role of Pharmacological Agents in Nerve Regeneration after Peripheral Nerve Repair

Mekaj¹

2017

Peripheral Nerve Regeneration - From Surgery to New Therapeutic Approaches Including Biomaterials and Cell-Based Therapies Deve

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Peripheral nerve injuries are frequent and represent a significant pathology of the peripheral nervous system because, despite operative techniques and successful microsurgical repair, in most cases, the nerve repair is followed by scar formation. Numerous investigations have been carried out with the aim of finding pharmacological substances that can prevent scar formation and speed up the regeneration of repaired nerves. This chapter is dedicated to the efforts of many researchers to find different pharmacological agents with local effects on the improvement of nerve regeneration. Numerous experiments have been carried out in mice and rabbits using hyaluronic acid, tacrolimus, cyclosporin A, melatonin, vitamin B12, methylprednisolone, riluzole and potassium and calcium channel blockers. In the experimental animal studies, topical pharmacological agents were used at the site of peripheral nerve repair. The effect of these substances is most commonly studied in sciatic nerve injury in experimental animals. Their effects were evaluated using a variety of methods, such as morphological, biomechanical, electrophysiological and functional evaluation, and the above-mentioned substances, have been shown to have neuroprotective and neuroregenerative properties though different mechanisms.

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Section: Tacrolimusmentioning

confidence: 99%

Section: Mechanisms Of Action Referencesmentioning

confidence: 99%

The Role of Pharmacological Agents in Nerve Regeneration after Peripheral Nerve Repair

Mekaj¹

2017

Peripheral Nerve Regeneration - From Surgery to New Therapeutic Approaches Including Biomaterials and Cell-Based Therapies Deve

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“…Local rapamycin can increase nerve regeneration [ 89 ]. FK506, a calcineurin inhibitor, enhances peripheral nerve regeneration and increases axonal sprouting [ 90 , 91 ]. FK506 has a dose dependent benefit, however it also has immunosuppressant properties [ 92 ].…”

Section: Exogenous Agents Improving Peripheral Nerve Regenerationmentioning

confidence: 99%

Advances and Future Applications of Augmented Peripheral Nerve Regeneration

Jones

Eisenberg

Jia

2016

IJMS

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Peripheral nerve injuries remain a significant source of long lasting morbidity, disability, and economic costs. Much research continues to be performed in areas related to improving the surgical outcomes of peripheral nerve repair. In this review, the physiology of peripheral nerve regeneration and the multitude of efforts to improve surgical outcomes are discussed. Improvements in tissue engineering that have allowed for the use of synthetic conduits seeded with neurotrophic factors are highlighted. Selected pre-clinical and available clinical data using cell based methods such as Schwann cell, undifferentiated, and differentiated stem cell transplantation to guide and enhance peripheral nerve regeneration are presented. The limitations that still exist in the utility of neurotrophic factors and cell-based therapies are outlined. Strategies that are most promising for translation into the clinical arena are suggested.

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“…FK506 can prevent T‐cell proliferation 13 and inhibit T‐cell function by binding to FK‐binding proteins (FKBPs) 14 . It has been shown that FK506 can promote peripheral nerve regeneration through suppression of fibroblast proliferation, which is activated by inflammatory cytokines at the site of nerve repair, 11,15 and can exert a maximal effect on nerve regeneration when administered at a high dose (5 to 10 mg/kg/d) after nerve crush injury in rats 12 . Recently, the sequential use of LPS and FK506 has been reported to be able to exert synergistic repair effects in neurotmesis 13 …”

Section: Introductionmentioning

confidence: 99%

Magnetic resonance imaging of enhanced nerve repair with mesenchymal stem cells combined with microenvironment immunomodulation in neurotmesis

et al. 2020

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Introduction:The immuno-microenvironment of injured nerves adversely affects mesenchymal stem cell (MSC) therapy for neurotmesis. Magnetic resonance imaging (MRI) can be used noninvasively to monitor nerve degeneration and regeneration. The aim of this study was to investigate nerve repair after MSC transplantation combined with microenvironment immunomodulation in neurotmesis by using multiparametric MRI.Methods: Rats with sciatic nerve transection and surgical coaptation were treated with MSCs combined with immunomodulation or MSCs alone. Serial multiparametric MRI examinations were performed over an 8-week period after surgery.Results: Nerves treated with MSCs combined with immunomodulation showed better functional recovery, rapid recovery of nerve T2, fractional anisotropy and radial diffusivity values, and more rapid restoration of the fiber tracks than nerves treated with MSCs alone.Discussion: Transplantation of MSCs in combination with immunomodulation can exert a synergistic repair effect on neurotmesis, which can be monitored by multiparametric MRI. K E Y W O R D Simmunomodulation, magnetic resonance imaging, mesenchymal stem cells, peripheral nerve injuries, tacrolimus, toll-like receptors Abbreviations: AD, axial diffusivity; BDNF, brain-derived neurotrophic factor; DTI, diffusion tensor imaging; DTT, diffusion tensor tractography; ELISA, enzyme-linked immunosorbent assay; FA, fractional anisotropy; FKBP, FK-binding protein; GDNF, glial cell-derived neurotrophic factor; GFP, green fluorescent protein; LPS, lipopolysaccharide; MD, mean diffusivity; MRI, magnetic resonance imaging; MSC, mesenchymal stem cell; PBS, phosphate-buffered saline; RD, radial diffusivity; SD, Sprague-Dawley; SFI, sciatic nerve function index; SPRR1A, small proline-rich protein 1A; TLR4, toll-like receptor 4; TNF-α, tumor necrosis factor-α.Zehong Yang and Chushan Zheng contributed equally to this work.

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Influence of Tacrolimus (FK506) on Nerve Regeneration Using Allografts: A Rat Sciatic Nerve Model

Cited by 27 publications

References 27 publications

The Role of Pharmacological Agents in Nerve Regeneration after Peripheral Nerve Repair

The Role of Pharmacological Agents in Nerve Regeneration after Peripheral Nerve Repair

Advances and Future Applications of Augmented Peripheral Nerve Regeneration

Magnetic resonance imaging of enhanced nerve repair with mesenchymal stem cells combined with microenvironment immunomodulation in neurotmesis

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