Traumatic Skeletal Muscle Injury Research Articles

Kinin receptors regulate skeletal muscle regeneration: differential effects for B1 and B2 receptors.

After traumatic skeletal muscle injury, muscle healing is often incomplete and produces extensive fibrosis. Bradykinin (BK) reduces fibrosis in renal and cardiac damage models through the B2 receptor. The B1 receptor expression is induced by damage, and blocking of the kallikrein-kinin system seems to affect the progression of muscular dystrophy. We hypothesized that both kinin B1 and B2 receptors could play a differential role after traumatic muscle injury, and the lack of the B1 receptor could produce more cellular and molecular substrates for myogenesis and fewer substrates for fibrosis, leading to better muscle healing. To test this hypothesis, tibialis anterior muscles of kinin receptor knockout animals were subjected to traumatic injury. Myogenesis, angiogenesis, fibrosis, and muscle functioning were evaluated. Injured B1KO mice showed a faster healing progression of the injured area with a larger amount of central nucleated fiber post-injury when compared to control mice. In addition, they exhibited higher neovasculogenic capacity, maintaining optimal tissue perfusion for the post-injury phase; had higher amounts of myogenic markers with less inflammatory infiltrate and tissue destruction. This was followed by higher amounts of SMAD7 and lower amounts of p-SMAD2/3, which resulted in less fibrosis. In contrast, B2KO and B1B2KO mice showed more severe tissue destruction and excessive fibrosis. B1KO animals had better results in post-injury functional tests compared to control animals. We demonstrate that injured skeletal muscle tissues have a better repair capacity with less fibrosis in the presence of B2 receptor and absence of B1 receptor, including better performances in functional tests.

Influence of estradiol deficiency on the acute inflammatory response following a traumatic skeletal muscle injury

Abstract Estradiol (E2) influences the inflammatory response. Research has shown that skeletal muscle chemokine mRNA expression and neutrophil infiltration after a traumatic freeze injury are blunted in ovariectomized mice treated with placebo compared to E2-treated mice. How E2 deficiency alters the acute muscle inflammatory response is unclear with potential mechanisms including alterations in the number of circulating leukocytes, leukocyte chemotaxis, and/or muscle chemokine expression. To investigate these possibilities, female C57BL/6J mice underwent a sham or ovariectomy (OVX) surgery, 21–28 d later tibialis anterior (TA) muscles were freeze injured. TA muscles and blood were collected 24 h post injury. Total white blood cell (149%) and monocytes (427%) were elevated in OVX compared to Sham mice but there was no difference in the neutrophil counts (p≥0.64). To determine if E2 deficiency impacts leukocyte chemotaxis, isolated leukocytes from bone marrow of non-injured Sham or OVX mice were placed in a transwell migration assay. OVX leukocytes had greater chemotaxis towards CXCL1 (37%), CXCL2 (43%), and CXCL5 (27%) than Sham. To examine if E2 deficiency alters muscle CXCL1 and CXCL5 protein content contributing to chemotaxis, ELISA assays were performed. Surprisingly, muscle CXCL1 and CXCL5 contents were similar between OVX and Sham. Collectively, mice lacking E2 have relatively high blood leukocytes and chemotaxis suggesting a greater acute inflammatory response which appears not to be driven by changes in muscle chemokine expression. Additional studies need to consider possible negative regulators of the acute inflammatory response in OVX muscle. Supported by DAL and GW (R01AG031743 & R01AG062899), and SLM (T32AR007612)

Effect of Phonophoresis and Copaiba Oil on Oxidative Stress Biomarkers after Skeletal Muscle Injury in Rats

The objective of this study was to analyze the effectiveness of phonophoresis with copaiba oil gel, in comparison to therapeutic pulsed ultrasound alone or topical application of copaiba oil gel, on oxidative stress after a traumatic muscle injury. Forty male Wistar rats were divided into five groups: control, muscle injury, therapeutic pulsed ultrasound (TPU), copaiba oil gel (CO) and TPU plus CO. TPU and CO application occurred at 2, 12, 24, 48, 72 and 96 h after injury. The gastrocnemius muscle was injured by mechanical trauma. Malondialdehyde (a lipoperoxidation marker) and superoxide dismutase and catalase (antioxidant enzymes) were assessed 98 h after muscle injury. All were elevated in the muscle injury group. There was a significant difference among treatment groups favoring TPU plus CO for reducing malondialdehyde levels, but all treatments reduced superoxide dismutase and catalase activity, with no between-groups difference. In conclusion, phonophoresis—the application of TPU plus CO—was superior to TPU or CO alone for reducing lipoperoxidation. Phonophoresis, TPU alone and CO were all effective in decreasing antioxidant enzyme activity after a traumatic skeletal muscle injury.

TLR4 Transactivates CD8+ T Lymphocytes upon Acute Sterile Tissue Injury.

Acute major tissue injury induces immune dysregulation that is characterized by the development of systemic sterile inflammation and an increased risk for opportunistic infections. Although the contribution of the innate immune system has been examined in detail, research on the impact of acute sterile tissue damage on the T cell compartment remains limited. In the current study, we used a clinically relevant mouse model for traumatic skeletal muscle injury to investigate the impact of sterile tissue damage on diverse subpopulations of CD4+ Th and CD8+ cytotoxic T cells in systemic and local lymphoid organs. For the first time, to our knowledge, we provide evidence that injury selectively induced the expression of the activation marker CD69 on naive and central/virtual memory CD8+ T cells in the lymph nodes but not in the spleen of male mice. CD4+ Th cells remained unaffected in both organs. The activation of CD8+ T cells was dependent on signaling through TLR4. Within a few hours, injury triggered the expression of IL-12 in the lymph nodes in a TLR4-dependent manner. Blocking of IL-12 prevented the activation of naive and central memory CD8+ T cells after injury. Thus, early after traumatic tissue damage, TLR4 transactivates naive and central/virtual memory CD8+ T cells through innate cytokines in local lymph nodes, where they might modulate forthcoming local immune responses.

Vascular endothelial ERp72 is involved in the inflammatory response in a rat model of skeletal muscle injury.

The vascular inflammatory response involves the coordinated action of a large network of molecular mediators and culminates in the transmigration of leukocytes into the site of inflammation. Inflammatory mediators include a variety of protein families, including adhesion molecules such as integrins and members of the immunoglobulin superfamily, as well as other cytokines and chemokines. In this study, a rat model of traumatic skeletal muscle injury was used to demonstrate endoplasmic reticulum resident protein 72 (ERp72) overexpression in the early phase of the inflammatory response that follows skeletal muscle injury. Reverse transcription-quantitative PCR, western blotting, dual-labeling immunohistochemistry and immunofluorescence experiments confirmed that ERp72 was expressed on the endothelial cells of blood vessels present at the injured area. In addition, a cell-based neutrophil adhesion assay indicated that a polyclonal antibody specific for ERp72 significantly reduced adhesion of neutrophils to activated human umbilical vein endothelial cells (35% reduction). These data suggested that ERp72 expression on vascular endothelial cells may play a role in skeletal muscle inflammation and could be considered as a target for the modulation of leukocyte-endothelial cell interactions in an inflammatory setting.

Skeletal muscle healing by M1-like macrophages produced by transient expression of exogenous GM-CSF

BackgroundAfter traumatic skeletal muscle injury, muscle healing is often incomplete and produces extensive fibrosis. The sequence of M1 and M2 macrophage accumulation and the duration of each subtype in the injured area may help to direct the relative extent of fibrogenesis and myogenesis during healing. We hypothesized that increasing the number of M1 macrophages early after traumatic muscle injury would produce more cellular and molecular substrates for myogenesis and fewer substrates for fibrosis, leading to better muscle healing.MethodsTo test this hypothesis, we transfected skeletal muscle with a plasmid vector to transiently express GM-CSF shortly after injury to drive the polarization of macrophages towards the M1 subset. C57BL/6 mouse tibialis anterior (TA) muscles were injured by contusion and electroporated with uP-mGM, which is a plasmid vector that transiently expresses GM-CSF. Myogenesis, angiogenesis, and fibrosis were evaluated by histology, immunohistochemistry, and RT-qPCR; subpopulations of macrophages by flow cytometry; and muscle functioning by the maximum running speed on the treadmill and the recovery of muscle mass.ResultsMuscle injury increased the number of local M1-like macrophages and decreased the number of M2-like macrophages on day 4, and uP-mGM treatment enhanced this variation. uP-mGM treatment decreased TGF-β1 protein expression on day 4, and the Sirius Red-positive area decreased from 35.93 ± 15.45% (no treatment) to 2.9% ± 6.5% (p < 0.01) on day 30. uP-mGM electroporation also increased Hgf, Hif1α, and Mtor gene expression; arteriole density; and muscle fiber number during regeneration. The improvement in the quality of the muscle tissue after treatment with uP-mGM affected the increase in the TA muscle mass and the maximum running speed on a treadmill.ConclusionCollectively, our data show that increasing the number of M1-like macrophages immediately after traumatic muscle injury promotes muscle recovery with less fibrosis, and this can be achieved by the transient expression of GM-CSF.

Autologous platelet rich plasma enhances satellite cells expression of MyoD and exerts angiogenic and antifibrotic effects in experimental rat model of traumatic skeletal muscle injury

Introduction: Skeletal muscle injuries comprise the greater part of sports-related injuries. Role of growth factors in healing of injured tissue encouraged the use of platelet-rich plasma (PRP).Aim of the work: We aimed to study the effect of PRP on skeletal muscle injury.Materials & Methods: Forty adult male rats were divided into four equal groups; control and 2, 7, 14 days after the injury. The injured muscles were either treated with PRP or left without treatment. The rats were sacrificed and the muscle specimens were processed for histological and immunohistochemical staining for detection of Anti-MyoD, anti-CD34 and anti TGFβ1 followed by morphometric study.Results: PRP treatment induced initial intense inflammatory response with neutrophils and macrophages cell infiltrate subsided in the 7th day. When compared to untreated groups, PRP treated ones showed significant increases in the mean number of regenerating muscle fibers (22.03±4.08) and angiogenesis (10.83±2.46) on the 7th day. The median number of MyoD immunopositive stellate cells showed a significant increase on the 2nd day ,72 (62-78) and then decrease on the 7th day; 28(22-33) to be non significant after 14th days; 4(3-5) of injury. A significant decrease in the mean area % of collagen deposition (2.27±.0.59, 3.68±0.72 and 4.76±0.82) and TGF β1 immunoexpression, medians; 5 (4.20-5.70), 2.50 (2.10-3.50) and 2.30( 1.60-3.20) after 2, 7 and 14 days, respectively, were observed.Conclusions: PRP could exert a promising effect on skeletal muscle injuries via enhancing myogenesis, neovascularization and reduction of fibrosis. Since autologous blood preparations are safe, PRP may serve as a valuable adjunct in management of such injuries.

Selective recruitment of non-classical monocytes promotes skeletal muscle repair.

Regeneration of traumatic defects in skeletal muscle requires the synchronized behavior of multiple cells that participate in repair. The inflammatory cascade that is rapidly initiated after injury serves as a powerful node at which to guide the progression of healing and influence tissue repair. Here, we examine the role that myeloid cells play in the healing of traumatic skeletal muscle injury, and leverage their pro-regenerative functions using local delivery of the immunomodulatory small molecule FTY720. We demonstrate that increasing the frequency of non-classical monocytes in inflamed muscle coincides with increased numbers of CD206+alternatively activated macrophages. Animals treated with immunomodulatory materials had greater defect closure and more vascularization in the acute phases of injury. In the later stages of repair, during which parenchymal tissue growth occurs, we observed improved regeneration of muscle fibers and decreased fibrotic tissue following localization of pro-regenerative inflammation. These results highlight non-classical monocytes as a novel therapeutic target to improve the regenerative outcome after traumatic skeletal muscle injury.

Dendritic Cell-Like Cells Accumulate in Regenerating Murine Skeletal Muscle after Injury and Boost Adaptive Immune Responses Only upon a Microbial Challenge.

Skeletal muscle injury causes a local sterile inflammatory response. In parallel, a state of immunosuppression develops distal to the site of tissue damage. Granulocytes and monocytes that are rapidly recruited to the site of injury contribute to tissue regeneration. In this study we used a mouse model of traumatic skeletal muscle injury to investigate the previously unknown role of dendritic cells (DCs) that accumulate in injured tissue. We injected the model antigen ovalbumin (OVA) into the skeletal muscle of injured or sham-treated mice to address the ability of these DCs in antigen uptake, migration, and specific T cell activation in the draining popliteal lymph node (pLN). Immature DC-like cells appeared in the skeletal muscle by 4 days after injury and subsequently acquired a mature phenotype, as indicated by increased expression of the costimulatory molecules CD40 and CD86. After the injection of OVA into the muscle, OVA-loaded DCs migrated into the pLN. The migration of DC-like cells from the injured muscle was enhanced in the presence of the microbial stimulus lipopolysaccharide at the site of antigen uptake and triggered an increased OVA-specific T helper cell type 1 (Th1) response in the pLN. Naïve OVA-loaded DCs were superior in Th1-like priming in the pLN when adoptively transferred into the skeletal muscle of injured mice, a finding indicating the relevance of the microenvironment in the regenerating skeletal muscle for increased Th1-like priming. These findings suggest that DC-like cells that accumulate in the regenerating muscle initiate a protective immune response upon microbial challenge and thereby overcome injury-induced immunosuppression.

Breaking the co-operation between bystander T-cells and natural killer cells prevents the development of immunosuppression after traumatic skeletal muscle injury in mice.

Nosocomial infections represent serious complications after traumatic or surgical injuries in intensive care units. The pathogenesis of the underlying immunosuppression is only incompletely understood. In the present study, we investigated whether injury interferes with the function of the adaptive immune system in particular with the differentiation of antigen-specific T helper (Th)-cell responses in vivo. We used a mouse model for traumatic gastrocnemius muscle injury. Ovalbumin (OVA), which served as a foreign model antigen, was injected into the hind footpads for determination of the differentiation of OVA-specific Th-cells in the draining popliteal lymph node (pLN). The release of interferon (IFN)-γ from OVA-specific Th-cells was impaired within 24 h after injury and this impairment persisted for at least 7 days. In contrast, the proliferation of OVA-specific Th-cells remained unaffected. Injury did not modulate the function of antigen-presenting cells (APCs) in the pLN. Adoptive transfer of total T-cells from pLNs of injured mice inhibited IFN-γ production by OVA-specific Th-cells in naive mice. Suppressed Th1 priming did not occur in lymphocyte-deficient mice after injury but was restored by administration of T-cells before injury. Moreover, the suppression of Th1 differentiation required the presence of natural killer (NK) cells that were recruited to the pLN after injury; this recruitment was dependent on lymphocytes, toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In summary, upon traumatic skeletal muscle injury T-cells and NK cells together prevent the development of protective Th1 immunity. Breaking this co-operation might be a novel approach to reduce the risk of infectious complications after injury.

Toll‐like and adenosine receptor expression in injured skeletal muscle

Many aspects of skeletal muscle regeneration are now considered to be controlled by the innate immune system, specifically macrophages, but the mechanisms for activation and modulation of the innate immune system during injury are not well understood. We analyzed the expression of toll-like receptors (TLRs) and adenosine receptors during traumatic skeletal muscle injury. mRNA expression and immunostaining of these receptors were evaluated in mouse skeletal muscle injured by freezing. Expression of nearly all mammalian TLRs was induced at 1 and/or 3 days postinjury with a common trend for higher expression at day 3. Injury also elicited a dramatic increase in the expression of adenosine receptors A(2B) and A(3) but not A(1) and A(2A) . Both receptor types may be potential targets for stimulation of skeletal muscle tissue regeneration and functional restoration after injury.

Repair of Traumatic Skeletal Muscle Injury with Bone-Marrow-Derived Mesenchymal Stem Cells Seeded on Extracellular Matrix

Skeletal muscle injury resulting in tissue loss poses unique challenges for surgical repair. Despite the regenerative potential of skeletal muscle, if a significant amount of tissue is lost, skeletal myofibers will not grow to fill the injured area completely. Prior work in our lab has shown the potential to fill the void with an extracellular matrix (ECM) scaffold, resulting in restoration of morphology, but not functional recovery. To improve the functional outcome of the injured muscle, a muscle-derived ECM was implanted into a 1 x 1 cm(2), full-thickness defect in the lateral gastrocnemius (LGAS) of Lewis rats. Seven days later, bone-marrow-derived mesenchymal stem cells (MSCs) were injected directly into the implanted ECM. Partial functional recovery occurred over the course of 42 days when the LGAS was repaired with an MSC-seeded ECM producing 85.4 +/- 3.6% of the contralateral LGAS. This was significantly higher than earlier recovery time points (p < 0.05). The specific tension returned to 94 +/- 9% of the contralateral limb. The implanted MSC-seeded ECM had more blood vessels and regenerating skeletal myofibers than the ECM without cells (p < 0.05). The data suggest that the repair of a skeletal muscle defect injury by the implantation of a muscle-derived ECM seeded with MSCs can improve functional recovery after 42 days.

Matrix metalloprotease-3 and tissue inhibitor of metalloprotease-1 mRNA and protein levels are altered in response to traumatic skeletal muscle injury

The purpose of this study was to characterize the time course of matrix metalloprotease-3 (MMP-3) and tissue inhibitor of metalloprotease-1 (TIMP-1) expression in mouse tibialis anterior (TA) muscle post-injury. Mice were anesthetized, the TA muscle exposed, and injury induced by applying a cold steel probe (-79 degrees C) to the muscle for 10 s. Muscle was collected from uninjured and injured legs at 3, 10, 24, 48, and 72 h post-injury. qRT-PCR, immunoblotting, and immunohistochemistry were used to quantify/localize MMP-3 and TIMP-1. MMP-3 transcripts increased 19- and 12-fold, 10 and 24 h post-injury (p < 0.01), respectively. TIMP-1 transcript levels increased 9-, 34-, and 60-fold, 10, 24, and 48 h post-injury (p = 0.01), respectively, with a subsequent decrease 72 h post-injury (p < 0.01). Protein levels of the pro-form of MMP-3 increased within 3 h post-injury and remained elevated (p < 0.05). Active MMP-3 decreased over time, reaching a 72% decrease 72 h post-injury (p < 0.05). TIMP-1 protein decreased 75% within 3 h post-injury, returning to baseline by 72 h post-injury. In response to injury, injured skeletal muscle preferentially produces increased levels of the latent form of the MMP-3 protein with a concomitant decrease in the active form, and a significant decrease in TIMP-1 expression. The altered pattern of MMP-3/TIMP-1 expression may be due to alterations in post-transcriptional mechanisms that are responsible for specific regulation of the MMP-3/TIMP-1 system. These data suggest that there is a disproportionate regulation of the MMP-3/TIMP-1 system following traumatic injury and this response may contribute to impaired extracellular matrix remodeling.

Alterations in mRNA and protein levels of metalloproteinases-2, -9, and -14 and tissue inhibitor of metalloproteinase-2 responses to traumatic skeletal muscle injury

This study characterizes the temporal relationship of membrane type-1 matrix metalloproteinase (MT1-MMP) and tissue inhibitor of metalloproteinase-2 (TIMP-2) expression in skeletal muscle following injury. Tibialis anterior (TA) muscles from 60 mice were exposed and injured by applying a cold steel probe (-79 degrees C) to the muscle for 10 s. Thereafter, TA muscles from uninjured and injured legs were collected at 3, 10, 24, 48, and 72 h postinjury for analysis of local MT1-MMP, TIMP-2, and matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) mRNA and protein content via quantitative RT-PCR, immunoblotting, zymography, and immunofluorescence. All data are expressed as fold change of injured leg vs. uninjured leg. MT1-MMP mRNA levels were decreased significantly at 48 and 72 h postinjury by approximately 9- and 21-fold, respectively (P < 0.01). Both TIMP-2 and MMP-2 mRNA expression significantly decreased in the injured leg by approximately 4- to 10-fold at 10-72 h postinjury (P < 0.01). MMP-9 mRNA expression was significantly increased at 10, 24, and 48 h postinjury by 6- (P < 0.05), 25-, and 12-fold (P < 0.01), respectively. Protein content of latent (63 kDa) MT1-MMP was decreased at 48 and 72 h postinjury by approximately 2-fold (P < 0.01). Content of the soluble (50 kDa) fragment of MT1-MMP was significantly increased by approximately 17-, 25-, and 67-fold at 24 (P < 0.05), 48, and 72 h (P < 0.01) postinjury, respectively. TIMP-2 protein levels diminished from 3 to 48 h postinjury by 1.5-fold to 1.8-fold (P < 0.01), before returning to baseline levels at 72 h postinjury. Zymography revealed visual increases in gelatinase activity in molecular weight regions corresponding to MMP-9 and MMP-2. In conclusion, skeletal muscle injury initiates a sequence of events in the MT1-MMP proteolytic cascade resulting in elevated levels of the soluble (50 kDa) fragment of MT1-MMP, which could enhance pericellular extracellular matrix remodeling.

Traumatic Skeletal Muscle Injury Results In Dual Regulation Of Myostatin Through Binding Protein Inhibition And Diminished Expression.

Traumatic Skeletal Muscle Injury Results In Dual Regulation Of Myostatin Through Binding Protein Inhibition And Diminished Expression.

Repair of traumatic skeletal muscle injury with bone marrow derived cells seeded on extracellular matrix

Surgical repair of a skeletal muscle injury resulting in tissue loss poses unique challenges to the surgeon. Despite the regenerative potential of skeletal muscle, if a significant amount of tissue is lost, skeletal muscle fibers will not grow to fill the injured area completely. Prior work in our lab has shown the potential to fill the void with an extracellular matrix scaffold (ECM), but functional recovery is limited. To improve the functional outcome of the injured muscle, a muscle‐derived ECM seeded with bone marrow derived cells was implanted into a 1 x 1 cm2 defect in the lateral gastrocnemius (LGAS) of Lewis rats. Without the addition of cells, the ECM repaired LGAS produced 76.4 ± 2.4% of the maximal force of the contralateral LGAS after 42 days of recovery. The LGAS repaired with ECM and cells produced 85.0 ± 4.2% of the contralateral LGAS. The specific tension was 87% and 94% of the contralateral limb for the ECM and ECM with cells groups respectively. The implanted ECM with cells had more blood vessels than the ECM without cells (p &lt; 0.05). The data suggest that the repair of a skeletal muscle defect injury by the implantation of a muscle‐derived ECM seeded with bone‐marrow derived cells can improve the functional outcome after 42 days. This is likely due to an increase in blood vessels and skeletal muscle fibers growing inside the implanted ECM. This work funded in part by the U.S. Army MRMC grant DAMD W81XWH‐06‐1‐0540.

Recombinant integrin CD11b A‐domain blocks polymorphonuclear cells recruitment and protects against skeletal muscle inflammatory injury in the rat

The beta2 integrin CD11b/CD18 (CR3) is a major adhesion receptor of neutrophils, normally utilized to fend off infections. This receptor contributes, however, to multiple forms of non-infectious inflammatory injury when dysregulated as shown in gene knock-outs and through the use of blocking monoclonal antibodies. The major ligand recognition site of CR3 has been mapped to the A-domain in the CD11b subunit (CD11bA). The recombinant form of this domain exhibits a ligand binding profile similar to that of the holoreceptor. To assess the potential anti-inflammatory activity of CD11bA as a competitive antagonist of CR3 in vivo, we assessed its effects on a developed animal model of traumatic skeletal muscle injury in the rat. Recombinant soluble rat CD11bA-domain fused to glutathione-S-transferase (GST) was administered intravenously in a single dose at 1 mg/kg to nine groups of Wistar rats, five in each group, 30 min before inducing traumatic skeletal muscle injury. Control animals received either a function-blocking anti-CD11b/CD18 monoclonal antibody (1 mg/kg), non-functional mutant forms of the CD11bA (D140GS/AGA, T209/A, D242/A), recombinant GST or buffer alone. In control animals, the wounded muscle showed oedema, erythrocyte extravasation and myonecrosis both within and outside the immediate wounded area (5-10 mm zone) and influx of neutrophils was detected 30 min post-wound, followed by a second wave 3 hr later. Wild-type CD11bA- or anti-CD11b monoclonal antibody (mAb)-treated rats showed a comparable and significant decrease in the number of infiltrating PMN (78 + 4%, n = 70 and 86 +/- 2%, n = 50, respectively) and preservation of the muscular fibres outside the immediate zone of necrosis (75 + 4%, n = 70, 84 +/- 1%, n = 50, respectively), compared to controls. These data demonstrate that CD11bA can be an effective tissue-preserving agent in acute inflammatory muscular injury.

Inflammatory mediators and skeletal muscle injury: a DNA microarray analysis.

Traumatic skeletal muscle injury causes a specific sequence of cellular events consisting of degeneration, inflammation, regeneration, and fibrosis. The role of early posttraumatic mechanisms, including acute inflammatory response, in muscle repair is not well understood. In the present study, oligonucleotide microarray analyses were used to examine the candidate genes that are involved in these early events of the muscle injury/repair process. cDNA was prepared from the injured and control tibialis anterior (TA) muscle of mice 24 h postinjury and labeled with the fluorescent dye Cy5 or Cy3 prior to hybridization to a DNA microarray. The microarray analysis, including 732 genes, was conducted in triplicate, and we describe only genes modulated by the injury showing a differential expression (both increased and decreased) 1.7-fold or greater (p < 0.05) from control uninjured TA muscle. Selected expression patterns were confirmed by other gene expression detection methods, including real-time reverse transcription-polymerase chain reaction (RT-PCR) and RNase protection assay (RPA) or immunohistochemistry detection methods. The upregulated genes (2.8%) were mainly associated with inflammation, oxidative stress, and cell proliferation, whereas the downregulated genes (3.2%) were related to metabolic and cell signaling pathways. In addition, the study suggested that chemokines, such as monocyte chemoattractant protein-1 (MCP-1), associated with monocyte/macrophage influx and activation, are abundantly expressed in postinjured muscle, and they might play a role in traumatic muscle injury/recovery processes.