Local Riluzole Release from a Thermosensitive Hydrogel Rescues Injured Motoneurons through Nerve Root Stumps in a Brachi
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ORIGINAL PAPER
Local Riluzole Release from a Thermosensitive Hydrogel Rescues Injured Motoneurons through Nerve Root Stumps in a Brachial Plexus Injury Rat Model Jintao Fang1 · Liang Li1,2 · Hong Zhai3 · Bengang Qin1 · Daping Quan3,4 · Enxian Shi1 · Menghai Zhu1 · Jiantao Yang1 · Xiaolin Liu1 · Liqiang Gu1 Received: 30 March 2020 / Revised: 22 August 2020 / Accepted: 29 August 2020 / Published online: 28 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The C5-C6 nerve roots are usually spared from avulsion after brachial plexus injury (BPI) and can thus be used as donors for nerve repair. A BPI rat model with C5-C6 nerve root stumps has been established in our previous work. The aim of this study was to test whether riluzole loaded into a thermosensitive hydrogel could applied locally in the nerve root stumps of this BPI rat model, thus increasing the reparative effect of the nerve root stumps. Nile red (a hydrophobic dye) was used as a substitute for riluzole since riluzole itself does not emit light. Nile red, loaded into a thermosensitive hydrogel, was added to the nerve root stumps of the BPI rat model. Additionally, eighteen rats, with operation on right brachial plexus, were evenly divided into three groups: control (Con), thermosensitive hydrogel (Gel) and thermosensitive hydrogel loaded with riluzole (Gel + Ri) groups. Direct nerve repair was performed after local riluzole release for two weeks. Functional and electrophysiological evaluations and histological assessments were used to evaluate the reparative effect 8 weeks after nerve repair. Nile red was slowly released from the thermosensitive hydrogel and retrograde transport through the nerve root stumps to the motoneurons, according to immunofluorescence. Discernible functional recovery began earlier in the Gel + Ri group. The compound muscle action potential, ChAT-expressing motoneurons, positivity for neurofilaments and S100, diameter of regenerating axons, myelin sheath thickness and density of myelinated fibers were markedly increased in the Gel + Ri group compared with the Con and Gel groups. Our results indicate that the local administration of riluzole could undergo retrograde transportation through C5-C6 nerve root stumps, thereby promoting neuroprotection and increasing nerve regeneration. Keywords Brachial plexus injury · Riluzole · Nerve root stumps · Local administration · Motoneuron protection · Nerve regeneration
Introduction
Jintao Fang, Liang Li and Hong Zhai have contributed equally to this study and should be considered as co-first authors.
Brachial plexus injury (BPI) is a severe event that occurs mostly in patients who are young and of productive ages, resulting in a serious impact on societal and economic development [1]. It has been reported that the C5-C6 nerve roots can be used as donors for nerve grafting because they
* Xiaolin Liu [email protected]
2
Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, China
* Liqiang Gu guliqiang1963@al
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