Redden James T, Deng Jingyao, Cohen David J, Schwartz Zvi, McClure Michael J
Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, Virginia, USA.
Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Adv Wound Care (New Rochelle). 2025 Feb;14(2):67-82. doi: 10.1089/wound.2024.0045. Epub 2024 Jul 26.
: Volumetric muscle loss results in intramuscular axotomy, denervating muscle distal to the injury and leading to paralysis, denervation, and loss of muscle function. Once the nerve is damaged, paralyzed skeletal muscle will atrophy and accumulate noncontractile connective tissue. The objective of this study was to determine differences in connective tissue, atrophy, and inflammatory signaling between two paralysis models, botulinum toxin (Botox), which blocks acetylcholine transmission while keeping nerves intact, and neurectomy, which eliminates all nerve-to-muscle signaling. : Twenty male Sprague Dawley rats were randomized and received a sciatic-femoral neurectomy (SFN), Botox-induced muscle paralysis of the proximal femur muscles, quadriceps femoris, hamstrings, and calf muscles (BTX), or sham. Muscle force was measured 52 days postsurgery, and samples were collected for histology, protein, and mRNA assays. SFN and BTX decreased twitch and tetanic force, decreased fiber size by twofold, and increased myogenic expression compared with controls. SFN increased the levels of all major extracellular matrix proteins correlating with fibrosis [ laminin, fibronectin, and collagen type(s) I, III, VI]. SFN also increased profibrotic and proinflammatory mRNA compared with BTX and controls. : SFN and BTX were similar in gross morphology and functional deficiencies. However, SFN exhibited a higher amount of fibrosis in histological sections and immunoblotting. The present study shows evidence that nerve signaling changes NF-κB and TGF-β signaling, warranting future studies to determine the mechanisms involved. These data indicate that nerve signaling may influence fibrogenesis following denervation, but the mechanisms involved may differ as a function of the method of paralysis.
容积性肌肉损失会导致肌内轴突切断，使损伤远端的肌肉失神经支配，进而导致瘫痪、去神经支配和肌肉功能丧失。一旦神经受损，瘫痪的骨骼肌就会萎缩并积累非收缩性结缔组织。本研究的目的是确定两种瘫痪模型之间在结缔组织、萎缩和炎症信号方面的差异，这两种模型分别是肉毒杆菌毒素（肉毒素），它能阻断乙酰胆碱传递同时保持神经完整，以及神经切除术，它会消除所有神经与肌肉之间的信号传递。
二十只雄性Sprague Dawley大鼠被随机分组，分别接受坐骨 - 股神经切除术（SFN）、肉毒素诱导的股骨近端肌肉、股四头肌、腘绳肌和小腿肌肉麻痹（BTX）或假手术。在术后52天测量肌肉力量，并采集样本进行组织学、蛋白质和mRNA检测。与对照组相比，SFN和BTX降低了抽搐和强直力量，使纤维大小减小了两倍，并增加了肌源性表达。SFN增加了与纤维化相关的所有主要细胞外基质蛋白的水平[层粘连蛋白、纤连蛋白和I、III、VI型胶原蛋白]。与BTX和对照组相比，SFN还增加了促纤维化和促炎mRNA。
SFN和BTX在大体形态和功能缺陷方面相似。然而，在组织学切片和免疫印迹中，SFN表现出更高程度的纤维化。本研究表明神经信号会改变NF - κB和TGF - β信号，这值得未来的研究来确定其中涉及的机制。这些数据表明神经信号可能影响去神经支配后的纤维生成，但所涉及的机制可能因瘫痪方法的不同而有所差异。
