The effects of FK1706 on nerve regeneration and bladder function recovery following an end-to-side neurorrhaphy in rats.

Wansheng Gao,Jianguo Wen,Xiangfei He,Yunlong Li

doi:10.18632/oncotarget.21718

Wansheng Gao, Jianguo Wen + Show 2 more

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https://doi.org/10.18632/oncotarget.21718

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Abstract

BackgroundImmunophilin ligands are neuroregenerative agents binding to FK506 binding proteins, by which stimulate recovery of neurons in a variety of injury nerves. FK1706 is a novel immunophilin ligand which has neuroprotective and neuroregenerative effects but without immunosuppressive activity. At present, most reports about FK1706 in ameliorating nerve injury and functional recovery are limited to cavernous nerve injury and erectile function recovery. This study aimed to demonstrate the effects of FK1706 on nerve regeneration and bladder function recovery following an end-to-side neurorrhaphy in rat models.MethodThe numbers of regenerated myelinated axons of the pelvic parasympathetic nerve (PPN) in the three groups’ rats (FK1706 + ETS, ETS and control groups) were evaluated. Their intravesical pressure (IVP), S100β and growth associated protein 43 (GAP43) expressions were also compared.ResultsIn FK1706 + ETS group, 90% the rats showed that the frequency of FG labeled neurons was larger than the 3.5 cutoff value, 100% the rats showed that the frequency of FG-FB double-labeled neurons was larger than the 5.5 cutoff value. The average maximum of IVP in FK1706 + ETS group reached 76.3% of the value in control group. Their average number of myelinated axons of regenerated PPN reached 80% of the amount in control group. The nerve regeneration-associated markers data indicated that the expression level of S100β and GAP43 in FK1706 + ETS group was approximately 2-fold higher than that of ETS group (P < 0.05).ConclusionsAfter end-to-side neurorrhaphy, FK1706 effectively enhanced the nerve regeneration and bladder function recovery.

Highlights

Neurogenic bladder because of all kinds of neural diseases such as neural tube defects, spinal cord injury, diabetes and peripheral nerve trauma, is a major medical problem affecting overall health for these patients
This study aimed to demonstrate the effects of FK1706 on nerve regeneration and bladder function recovery following an end-to-side neurorrhaphy in rat models
In FK1706 + ETS group, 90% the rats showed that the frequency of FG labeled neurons was larger than the 3.5 cutoff value, 100% the rats showed that the frequency of FG-FB double-labeled neurons was larger than the 5.5 cutoff value

Summary

Introduction

Neurogenic bladder because of all kinds of neural diseases such as neural tube defects, spinal cord injury, diabetes and peripheral nerve trauma, is a major medical problem affecting overall health for these patients. 10% of these patients eventually died from renal failure caused by neurogenic bladder dysfunction (NBD) each year [1]. NBD has been treated by intradural End-to-side (ETS) neurorrhaphy of lumbar and sacral nerve, ameliorating urination dysfunction and hydronephrosis for these patients [2]. The results of nerve repair and bladder function reconstruction remain unsatisfactory after ETS neurorrhaphy since the donor nerve is intact without any injury which reduces the effect of axonal regrowth. How to further improve the nerve regeneration and bladder function recovery is a challenge for urologists and neurosurgeons at present. Immunophilin ligands are neuroregenerative agents binding to FK506 binding proteins, by which stimulate recovery of neurons in a variety of injury nerves. This study aimed to demonstrate the effects of FK1706 on nerve regeneration and bladder function recovery following an end-to-side neurorrhaphy in rat models

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