Effects of topically administered FK506 on sciatic nerve regeneration and reinnervation after vein graft repair of short nerve gaps

Azizi, Saeed; Mohammadi, Rahim; Amini, Keyvan; Fallah, Roza

doi:10.3171/2012.1.focus11320

Cited by 33 publications

(37 citation statements)

References 28 publications

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“…Neurones can sprout scattered neurites thus leading to hyperesthesia if the neurotrophic factors act on normal sensory neurones (27). No such phenomenon was observed in neither peripheral nerves nor nervus centralis after use of FK506 (28). In addition, all polypeptide neurotrophic factors only function after being intrathecally injected and FK506 and derivatives can penetrate the blood.…”

Section: Discussionmentioning

confidence: 99%

Experimental research on end-to-side anastomosis of peripheral nerves and effect of FK506 on end-to-side anastomosis

Lm¹,

Yx²,

Xp³

et al. 2014

BLL

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Abstract:Objective: To study the effects of end-to-side anastomosis of initially-denatured nerves at different times. Method: 60 male Wistar albino rats were used to fabricate animal models for the experiment on end-to-side anastomosis of peripheral nerves and 50 female Wistar albino rats were used to fabricate animal models for the experiment on the effect of FK506 on end-to-side anastomosis. Bilateral common peroneal nerve, tibialis anterior muscle electrophysiological and histological examinations, tibialis anterior muscle wet muscle weight determination, and motor end plate examination were performed 3 months after operation.Results: All recovery rates of action potential, single muscle contraction force and tetanic contraction force of the FK506 experimental group are signifi cantly higher than those of the control group and the sectional area of muscle fi ber is also higher than that of the control group of normal saline. Conclusion:The best time for end-to-side anastomosis of nerves should be controlled within 2 weeks and the effect of end-to-side anastomosis of nerves will gradually become unsatisfactory. FK506 plays a role in promoting functional rehabilitation following nerve end-to-side anastomosis (Tab. 7, Fig. 4, Ref. 31). Text in PDF www.elis.sk.

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Section: Discussionmentioning

confidence: 99%

Experimental research on end-to-side anastomosis of peripheral nerves and effect of FK506 on end-to-side anastomosis

Lm¹,

Yx²,

Xp³

et al. 2014

BLL

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“…Additionally, the results of the use of tacrolimus in peripheral nerve regeneration differ in the literature. The relative variability of the results of experimental studies of nerve injures can be explain by the variety of models and testing methods used [91]. Prior studies have shown that FK506-FKBP12 interaction may lead to a neuroregenerative effect through increased neuronal expression of a growth cone-associated protein GAP-43, but there is evidence that this occurs through inactivation of neuronal nitric synthetase [92,93].…”

Section: Tacrolimusmentioning

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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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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“…The transplantation of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) into a 2 mm long sciatic nerve gap induced axon regeneration across the gap and recovery in nerve function [343,344]. It has been proposed that hepatocyte growth factor and insulin-like growth factor-binding protein-1 released from the hESC-MSCs are responsible for promoting the axon regeneration [344].…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

Kuffler¹

2015

Int J Neurorehabilitation Eng

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Repairing Peripheral Nerves following Traumas Nerve crushWithin several days of crushing a peripheral nerve, the injured axons begin to regenerate through their distal pathway until they reach their original targets with which they restore neurological function. The larger the number of axons that regenerate through the distal nerve, the greater the extent of neurological recovery [1][2][3]. The number of axons that regenerate, and thus neurological recovery, is influenced by the physiological state of the distal denervated nerve pathway [4][5][6][7].Following a peripheral nerve crush, the injured axons begin to regenerate within 2 days of injury [8]. They may regenerate to their targets through their original pathway in association with and promoted by its Schwann cells, the neurotrophic factors they release, and the Schwann cell extracellular matrix [1,4,[9][10][11][12][13][14]. Thus, the distal nerve provides a simple means for promoting and directing the regenerating axons to their original targets [15][16][17][18]. However, when a nerve has a gap, the gap must be bridged with a material that is permissive to and promotes axon regeneration across the entire gap to reach the distal nerve stump, through which the axons must then be able to regenerate.The Schwann cells in the denervated distal nerve release neurotrophic factors that promote axon regeneration, but also release extracellular matrix components that promote and inhibit axon regeneration [19][20][21][22][23][24][25][26]. Thus, regeneration through the distal nerve is a balance of the influences of factors that both promote and inhibit regeneration. If the Schwann cells are present, such as after a simple nerve crush, virtually 100% of the axons regenerate and they innervate all the denervated synaptic sites. If the Schwann cells within the distal nerve pathway are killed, leaving only the extracellular matrix intact, the number of axons that regenerates to their targets decreases by 94%. This is because the factors required to trigger the regenerating axons to branch at extracellular matrix branch points are missing, axons do not branch, and therefore each axon reinnervates only a single denervated muscle fiber. Thus, Schwann cells along the distal nerve pathway and a AbstractFollowing a peripheral nerve crush, or when a peripheral the nerve is transected and the nerve stumps anastomosed, neurological recovery is generally excellent. This is because the axons merely have to regenerate through the distal portion of the nerve through the existing extracellular matrix of the denervated Schwann cells that direct and promote them to their distant denervated motor and sensory targets. However, when a length of a peripheral nerve is destroyed, and anastomosis is not possible, the standard surgical repair technique is to graft a length/s of autologous sensory nerve into the gap. Neurological recovery is generally good if the nerve gap is <2 cm in length, the repair is performed <4 months post trauma, and the patients are <25 years of age. Because the nerve ...

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Effects of topically administered FK506 on sciatic nerve regeneration and reinnervation after vein graft repair of short nerve gaps

Cited by 33 publications

References 28 publications

Experimental research on end-to-side anastomosis of peripheral nerves and effect of FK506 on end-to-side anastomosis

Experimental research on end-to-side anastomosis of peripheral nerves and effect of FK506 on end-to-side anastomosis

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

Promoting Axon Regeneration and Neurological Recovery Following Traumatic Peripheral Nerve Injuries

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