b1fd73604178e5fdf0e1c97fb3d169c6 cells_a2021v10n1p22.pdf 2849ba06da0fcc357833e996fede7b3800aac008 cells_a2021v10n1p22.pdf f11fad3f6046bc44a36c8b30b923d330a45c02e874316e6e1c58dbf1ac8a9154 cells_a2021v10n1p22.pdf Title: NeuroHeal Improves Muscle Regeneration after Injury Subject: Musculoskeletal injuries represent a challenging medical problem. Although the skeletal muscle is able to regenerate and recover after injury, the process engaged with conservative therapy can be inefficient, leading to a high re-injury rate. In addition, the formation of scar tissue implies an alteration of mechanical properties in muscle. There is still a need for new treatments of the injured muscle. NeuroHeal may be one option. Published studies demonstrated that it reduces muscle atrophy due to denervation and disuse. The main objective of the present work was to assess the potential of NeuroHeal to improve muscle regeneration after traumatic injury. Secondary objectives included characterizing the effect of NeuroHeal treatment on satellite cell biology. We used a rat model of sport-induced injury in the gastrocnemius and analyzed the effects of NeuroHeal on functional recovery by means of electrophysiology and tetanic force analysis. These studies were accompanied by immunohistochemistry of the injured muscle to analyze fibrosis, satellite cell state, and fiber type. In addition, we used an in vitro model to determine the effect of NeuroHeal on myoblast biology and partially decipher its mechanism of action. The results showed that NeuroHeal treatment advanced muscle fiber recovery after injury in a preclinical model of muscle injury, and significantly reduced the formation of scar tissue. In vitro, we observed that NeuroHeal accelerated the formation of myotubes. The results pave the way for novel therapeutic avenues for muscle/tendinous disorders. Keywords: muscle regeneration; NeuroHeal; satellite cells; Sirtuin 1; sport injury Author: Sara Marmolejo-Martínez-Artesero, David Romeo-Guitart, Vanesa Venegas, Mario Marotta and Caty Casas Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Dec 26 08:17:35 2020 CET ModDate: Sat Dec 26 09:45:13 2020 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3758453 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MWHIBA+VnURWPalladioL Type 1 Custom yes yes no 10 0 LTHWDO+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 OXJQPA+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 BYRWCN+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 PFKOHU+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 58 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 62 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 66 0 XEYJZU+CMSY10 Type 1 Builtin yes yes no 81 0 LEVXPH+EURM10 Type 1 Builtin yes yes no 85 0 PPVPWG+URWPalladioL-BoldItal Type 1 Custom yes yes no 104 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:56:10 CEST RepresentationInformation: cells_a2021v10n1p22.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 11:50:21 CEST Size: 3758453 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 286 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Muscle Injury Model Destination: subsection.2.1 Item: Title: Drug Treatment Destination: subsection.2.2 Item: Title: Electrophysiology Destination: subsection.2.3 Item: Title: Measurement of Muscle Force Destination: subsection.2.4 Item: Title: Histology Destination: subsection.2.5 Item: Title: Myoblast Differentiation and Analysis Destination: subsection.2.6 Item: Title: Statistical Analysis Destination: subsection.2.7 Item: Title: Results Destination: section.3 Children: Item: Title: Text Destination: subsection.3.1 Children: Item: Title: NeuroHeal Accelerates Muscle Fiber Function Recovery Destination: subsubsection.3.1.1 Item: Title: NeuroHeal Modulates Fiber Regeneration and Reduces Collagen Deposition Destination: subsubsection.3.1.2 Item: Title: NeuroHeal Influences Muscle Satellite Cells Destination: subsubsection.3.1.3 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: section.4 Info: Title: NeuroHeal Improves Muscle Regeneration after Injury Author: Sara Marmolejo-Martínez-Artesero, David Romeo-Guitart, Vanesa Venegas, Mario Marotta and Caty Casas Subject: Musculoskeletal injuries represent a challenging medical problem. Although the skeletal muscle is able to regenerate and recover after injury, the process engaged with conservative therapy can be inefficient, leading to a high re-injury rate. In addition, the formation of scar tissue implies an alteration of mechanical properties in muscle. There is still a need for new treatments of the injured muscle. NeuroHeal may be one option. Published studies demonstrated that it reduces muscle atrophy due to denervation and disuse. The main objective of the present work was to assess the potential of NeuroHeal to improve muscle regeneration after traumatic injury. Secondary objectives included characterizing the effect of NeuroHeal treatment on satellite cell biology. We used a rat model of sport-induced injury in the gastrocnemius and analyzed the effects of NeuroHeal on functional recovery by means of electrophysiology and tetanic force analysis. These studies were accompanied by immunohistochemistry of the injured muscle to analyze fibrosis, satellite cell state, and fiber type. In addition, we used an in vitro model to determine the effect of NeuroHeal on myoblast biology and partially decipher its mechanism of action. The results showed that NeuroHeal treatment advanced muscle fiber recovery after injury in a preclinical model of muscle injury, and significantly reduced the formation of scar tissue. In vitro, we observed that NeuroHeal accelerated the formation of myotubes. The results pave the way for novel therapeutic avenues for muscle/tendinous disorders. 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