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

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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在臂丛神经损伤大鼠模型中,热敏水凝胶局部释放利鲁唑可通过神经根残端拯救受伤的运动神经元

DOI:
10.1007/s11064-020-03120-0
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发表时间:
2020-09
影响因子:
4.4
通讯作者:
Liqiang Gu
Liqiang Gu
中科院分区:
医学3区
文献类型:
--
作者:
Jintao Fang;Liang Li;Hong Zhai;Bengang Qin;Daping Quan;Enxian Shi;Menghai Zhu;Jiantao Yang;Xiaolin Liu;Liqiang Gu

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C5-C6神经根在臂丛神经损伤(BPI)后通常免于撕脱,因此可以用作神经修复的供体。我们在前期工作中建立了C5-C6神经根残端BPI大鼠模型。本研究的目的是测试负载到热敏水凝胶中的利鲁唑是否可以局部应用于该BPI大鼠模型的神经根残端,从而增加神经根残端的修复效果。尼罗红(一种疏水性染料)被用作利鲁唑的替代品,因为利鲁唑本身不发光。将装载到热敏水凝胶中的尼罗红添加到BPI大鼠模型的神经根残端。另将18只右侧臂丛神经手术大鼠随机分为对照组(Con)、温敏凝胶组(Gel)和温敏凝胶+利鲁唑组(Gel + Ri)。局部释放利鲁唑两周后进行直接神经修复。神经修复后8周,采用功能、电生理和组织学评价修复效果。根据免疫荧光,尼罗红从温敏水凝胶中缓慢释放,并通过神经根残端逆行转运到运动神经元。在凝胶+ Ri组中,明显的功能恢复开始得更早。Gel + Ri组的复合肌肉动作电位、ChAT阳性运动神经元、神经丝和S100阳性表达、再生轴突直径、髓鞘厚度和有髓纤维密度均显著高于Con组和Gel组。我们的研究结果表明,局部给药利鲁唑可以通过C5-C6神经根残端进行逆行运输,从而促进神经保护和增加神经再生。
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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发表时间: 1997-05-01
影响因子: 2.9
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