Neuromuscular Electrical Stimulation Induces Beneficial Adaptations in the Extracellular Matrix of Quadriceps Muscle After Anterior Cruciate Ligament Transection of Rats

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Abstract
Objective The aim of this study was to assess the effect of neuromuscular electrical stimulation (NMES) on the extracellular matrix remodeling of the quadriceps muscle after anterior cruciate ligament (ACL) transection in rats. The hypothesis of this study was that ACL transection would induce maladaptive modifications in the extracellular matrix through the increase in connective tissue (CT) accumulation and net degradation of type IV collagen of the quadriceps muscle. In addition, clinical-like NMES, applied to the quadriceps muscle immediately after the ACL transection, would reduce the accumulation of the CT content and net degradation of type IV collagen. Design Wistar male rats were randomized into five different groups: ACL (surgery and ACL transection), Sham (surgery without ACL transection), ACLES (surgery, ACL transection, and NMES), ShamES (surgery without ACL transection, but NMES), and Control (intact animals). The vastus medialis, rectus femoris, and vastus lateralis muscles of the quadriceps were harvested 1, 2, 3, 7, and 15 days after surgery. Matrix metalloproteinase–2 (MMP-2) (messenger RNA [mRNA] levels and activity), collagen IV (mRNA and protein levels), and CT density were assessed. Results The ACL transection increased the CT content and MMP-2 mRNA levels and decreased collagen IV mRNA and protein levels. NMES minimized the CT density in all muscles and reduced the MMP-2 mRNA levels mainly in the vastus lateralis muscle at 7 days. Moreover, type IV collagen mRNA levels were increased in all muscles at 7 days, as was the protein level only at 15 days, in the NMES groups. Conclusions This study showed that ACL transection increases CT content and MMP-2 mRNA levels and induces rapid changes in basement membranes, causing net degradation of type IV collagen during the first 2 wks after ACL injury. Furthermore, clinical-like NMES minimized the accumulation of CT density, regulated the MMP-2 mRNA levels, and increased both type IV collagen mRNA and protein levels.

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