Orally administered boldine reduces muscle atrophy and promotes neuromuscular recovery in a rodent model of delayed nerve repair.
Orally administered boldine reduces muscle atrophy and promotes neuromuscular recovery in a rodent model of delayed nerve repair.
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DOI：
10.3389/fncel.2023.1240916
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发表时间：
2023
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
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由于长时间的肌肉去神经支配，周围神经损伤常常导致功能恢复不良。特别是，缺乏轴突接触，失神经支配的肌肉可以经历不可挽回的萎缩和减少的接受神经再支配随着时间的推移，最终降低了有意义的神经肌肉恢复的可能性。虽然创新的手术方法可以通过重新路由相邻的未受伤的轴突来最大限度地减少去神经支配的有害影响，但没有临床可用的方法来保留去神经肌肉的神经支配能力。据报道，阻断肌内连接蛋白半通道形成可在体外改善肌肉神经支配并在体内防止萎缩。因此，目前的研究调查口服boldine，连接蛋白半通道抑制剂，对失神经相关的肌肉变化和神经再生延迟周围神经修复的大鼠模型的影响。我们发现，每日boldine管理显着增强诱发反应，在胫前肌腓总神经切断后2周，并减少肌内连接蛋白43和45的表达，神经内雪旺氏细胞表达连接蛋白43，和肌纤维萎缩至4周后切断。其他动物在初次横断损伤后4周接受了交叉神经修复手术（胫骨至腓总神经缝合术）。在此，我们发现boldine治疗的动物在修复后6周神经电生理活动升高，肌纤维成熟度更高。这些研究结果表明，boldine可能是一种有前途的药理学方法，以尽量减少长期去神经支配的有害影响，并进一步优化，可以提高神经修复后的功能恢复水平。
Peripheral nerve injury often results in poor functional recovery due to a prolonged period of muscle denervation. In particular, absent axonal contact, denervated muscle can undergo irrevocable atrophy and diminished receptiveness for reinnervation over time, ultimately reducing the likelihood for meaningful neuromuscular recovery. While innovative surgical approaches can minimize the harmful effects of denervation by re-routing neighboring—otherwise uninjured—axons, there are no clinically-available approaches to preserve the reinnervation capacity of denervated muscles. Blocking intramuscular connexin hemichannel formation has been reported to improve muscle innervation in vitro and prevent atrophy in vivo. Therefore, the current study investigated the effects of orally administered boldine, a connexin hemichannel inhibitor, on denervated-related muscle changes and nerve regeneration in a rat model of delayed peripheral nerve repair. We found that daily boldine administration significantly enhanced an evoked response in the tibialis anterior muscle at 2 weeks after common peroneal nerve transection, and decreased intramuscular connexin 43 and 45 expression, intraneural Schwann cell expression of connexin 43, and muscle fiber atrophy up to 4 weeks post transection. Additional animals underwent a cross nerve repair procedure (tibial to common peroneal neurorrhaphy) at 4 weeks following the initial transection injury. Here, we found elevated nerve electrophysiological activity and greater muscle fiber maturation at 6 weeks post repair in boldine treated animals. These findings suggest that boldine may be a promising pharmacological approach to minimize the deleterious effects of prolonged denervation and, with further optimization, may improve levels of functional recovery following nerve repair.
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影响因子：
5.6
作者：
Cea LA;Fernández G;Arias-Bravo G;Castillo-Ruiz M;Escamilla R;Brañes MC;Sáez JC
通讯作者：
Sáez JC
影响因子：
4.1
作者：
Katiyar, Kritika S.;Burrell, Justin C.;Cullen, D. Kacy
通讯作者：
Cullen, D. Kacy
影响因子：
5.6
作者：
Gómez GI;Velarde V
通讯作者：
Velarde V
影响因子：
5.7
作者：
Katiyar, Kritika S.;Struzyna, Laura A.;Cullen, D. Kacy
通讯作者：
Cullen, D. Kacy
影响因子：
18.9
作者：
Burrell JC;Das S;Laimo FA;Katiyar KS;Browne KD;Shultz RB;Tien VJ;Vu PT;Petrov D;Ali ZS;Rosen JM;Cullen DK
通讯作者：
Cullen DK