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Local Riluzole Release from a Thermosensitive Hydrogel Rescues Injured Motoneurons through Nerve Root Stumps in a Brachial Plexus Injury Rat Model

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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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Numbers 81572130, 81601057, and 81871787) and the Natural Science Foundation of Guangdong Province (Grant Numbers 2019A1515012057, 2018A030310254,2015A030310350 and 2015A030313194).

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Contributions

JY and LG carried out the concept, and JF, LL and HZ participated in the design of this study and performed the experiments and statistical analysis. These three authors contributed to this work equally and should be considered co-first authors. BQ, ES and MZ also performed experiments and collected important background information. DQ and HZ designed and provided the thermosensitive hydrogel. DQ, XL, JY and LG provided technical support. JF, LL and HZ drafted the paper. JY and LG revised the paper. All authors read and approved the final manuscript.

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Correspondence to Xiaolin Liu or Liqiang Gu.

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The authors have declared no conflict of interest.

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All animal studies have been approved by The Institute Research Medical Ethics Committee of Sun Yat-Sen University (Application ID: [2016] 150).

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Fang, J., Li, L., Zhai, H. et al. Local Riluzole Release from a Thermosensitive Hydrogel Rescues Injured Motoneurons through Nerve Root Stumps in a Brachial Plexus Injury Rat Model. Neurochem Res 45, 2800–2813 (2020). https://doi.org/10.1007/s11064-020-03120-0

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