Induction of muscle weakness by local inflammation: an experimental animal model

Abstract

Objective and design-The objective of this study was to characterize the response of skeletal muscle to a localized inflammation induced by the inflammatory agent casein.Methods-An inflammatory agent, casein, was injected into the right hindlimb and saline was injected into the left hindlimb of normal adult mice, once daily for six consecutive days. Inflammatory response was monitored by immunohistochemical labeling of leukocytes. Muscle protein levels were determined by electrophoresis and muscle function was determined by isometric force measurements.Results-Local inflammation was induced by casein in association with the accumulation of extensive neutrophils and macrophages in the solues muscle. This local inflammation resulted in a shift in myosin heavy chain (MHC) isoform expression and a significant reduction in total MHC concentration in the soleus. Maximal twitch and tetanic forces were significantly reduced in the inflamed soleus. Contractile function in soleus was fully restored after two weeks of recovery, along with the restoration of protein concentration and the disappearance of inflammatory cells.Conclusion-This study establishes a unique and robust model in which mechanisms of local inflammation induced muscle protein degradation, reduction of contractile force, and subsequent recovery from this condition can be further studied.

Tumor growth increases neuroinflammation, fatigue and depressive-like behavior prior to alterations in muscle function

“…Contractile properties of freshly isolated hindlimb muscles were determined, as described in detail previously (Bicer et al, 2009). In brief, mice were euthanized with CO 2 inhalation and one soleus muscle and one EDL muscle were removed and placed in oxygenated Ringer’s solution.…”

“…One muscle was maintained in oxygenated Ringer’s solution in a petri dish at room temperature while contractile measurements were made on the other muscle. The order in which the soleus and EDL were studied was alternated between experiments and it was previously determined that this did not impact the results (Bicer et al, 2009). All of the measurements were made at room temperature (21.2–23.8°C).…”

“…Five tetani, spaced 2 minutes apart, were studied in each muscle and the means were calculated. Maximal twitch and tetanic forces were also normalized to muscle cross-sectional area which was estimated from muscle mass and length measurements (Bicer et al, 2009). After a five minute rest, fatigue resistance was measured by stimulating the muscle with trains at 1 Hz consisting of pulses (pulse duration 0.1 ms) at 70 Hz for 400 ms. A fatigue index was quantitated as the peak force during the train at 2 minutes divided by the peak force during the initial train.…”

Treatment of Tourniquet-Induced Ischemia Reperfusion Injury with Muscle Progenitor Cells

“…The beneficial effect of MPCs could also be through reducing inflammation. Inflammation can reduce muscle-specific force by interfering with contractile protein synthesis and degradation, altering contractile protein force generation capacity, and affect E-C coupling by reducing calcium sensitivity and causing mitochondria dysfunction through secretion of inflammatory cytokines and reactive oxygen and nitrogen species [49][50][51]. In addition, inflammatory cells can induce fibrosis through secretion of TGF-b1 and MCP-1 [52,53], thus increasing non-contractile elements in muscle tissue.…”

Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

“…Most of these investigations were focused on bovine casein-derived peptides. Furthermore, bovine casein preparations are often used to induce experimental inflammation in animal models by injection (22)(23)(24)(25). The mammary gland was believed to be the sole site of expression for caseins (26), but a transgenic-mouse model showed elevated serum levels of human GM-CSF expressed under the control of the rodent as1-casein gene (27).…”