Electrical Stimulation Based on Chronaxie Increases Fibrosis and Modulates TWEAK/Fn14, TGF-β/Myostatin, and MMP Pathways in Denervated Muscles

Abstract

Electrical stimulation applied to denervated muscles induced muscle fibrosis and atrophy, as well as loss of performance. The TWEAK/Fn14 system, TGF-beta/myostatin pathway, and MMP activity seem to be involved in these deleterious changes.

Electrical stimulation delays reinnervation in denervated rat muscle

“…Nevertheless, on the 14 th day, whilst D15 improved the neuromuscular performance, increasing SFI, DES15d remained similar to its values observed on the 6 th day (Table ), with a difference between groups ( P = 0.001). Data are also published elsewhere (Pinheiro‐Dardis and Russo; ahead of print).…”

“…Morphometric analysis was performed according to Pinheiro‐Dardis and Russo . Histological cross‐sections (10 μm) were obtained with a cryostat microtome (Microm HE 505, Jena, Germany), through the middle belly of the TA muscles.…”

Electrical Stimulation of Denervated Rat Skeletal Muscle Retards Capillary and Muscle Loss in Early Stages of Disuse Atrophy

“…In contrast, other preclinical studies have demonstrated no beneficial effects of chronaxie-based ES (frequency: 20 Hz; pulse duration: twice the chronaxie value; 3 s on, 6 s off) on nerve crush-induced muscle fiber atrophy and muscle excitability [11]. In fact, chronaxie-based ES has been reported to induce muscle fibrosis and atrophy in denervated muscles [12]. Furthermore, although high-intensity (16 mA) ES was effective in retarding denervated muscle atrophy, it may have adverse effects on the regeneration of nerve terminals in the neuromuscular junction and/or the membrane systems involved in excitation-contraction coupling [13].…”

Fast repetitive stretch suppresses denervation‐induced muscle fibrosis

“…30,31 In the present study, expressions of all mRNA were up-regulated from 3 to 7 d after denervation and maintained to 9 d. Increases in TGF-β1, α-SMA, COL-1α2, and COL-3α1 mRNA in denervated muscle were reported in some studies of gastrocnemius, soleus, and sternocleidomastoid muscles in rodents. [19][20][21][22]32 Palumbo-Zerr et al 33 demonstrated that TGF-β1 induced up-regulation of collagen types 1α1 and 1α2 (encoding types of collagen), which promote fibrosis in human and mouse skin, but the relationship between TGF-β1 and collagen type 1α2 in muscle remains unclear.…”

“…endomysium, perimysium, and epimysium 16,17 and TGF-β1 have been detected in denervated muscle. 9,[18][19][20][21][22] In addition, connective tissue growth factor, a profibrotic cytokine, is up-regulated by TGF-β1 and induces expression of ECM molecules, such as collagen type 1α2 (COL-1α2). [23][24][25] Hypoxia-inducible factor (HIF)-1α, one of the major proteins expressed under hypoxic state, is increased with physical exercise, 26 hypoxia, 27 and stretching 28…”