Pathophysiology

Background: The functional state of skeletal muscle is governed by the interaction of mechanical loading, neural control, and proprioceptive afferentation. Nonetheless, the relative impact of the disruption of these components on muscle function and structure remains insufficiently characterized. Methods: In the present study, we investigated three rat models of muscle disuse and two combined models: hindlimb unloading (n = 40), denervation (D, n = 40), tenotomy (T, n = 40), and the combinations HU + D (n = 8) and HU + T (n = 8), with the cumulative effects evaluated at 7, 14, 35, and 50 days. Functional changes were assessed using electrophysiological methods (M-response recording), and structural changes were evaluated by histological, immunohistochemical, and immunofluorescence analysis. Results: The disuse models elicited significantly distinct trajectories of muscle maladaptation. Hindlimb unloading induced coordinated functional and structural remodeling; denervation provoked early functional decline followed by structural changes; tenotomy largely preserved functional activity despite progressive structural remodeling. The combination of denervation with unloading partially attenuated the negative effects, whereas the combination of unloading and tenotomy led to functional enhancement in some cases. These findings provide insight into the degree of convergence, additivity, and synergy of the disruption of regulatory components and indicate that reduced electrical activity is not invariably associated with synchronous structural degradation, revealing a functional–structural dissociation wherein functional status fails to reflect structural integrity. Conclusions: This observation suggests a previously unrecognized mechanism of maladaptation, which diverges from classical atrophy, broadening our understanding of muscle disuse physiology and offering new perspectives for the development of preventive and therapeutic strategies against atrophic processes.

The global incidence of diseases caused by Mycobacterium abscessus (Mab), which is a nontuberculous mycobacterium (NTM), is increasing, driven by improved diagnostics and environmental changes that disrupt natural reservoirs in soil and water. These disruptions facilitate contamination of water systems. Immunocompromised individuals, particularly those with cystic fibrosis or chronic obstructive pulmonary disease, are at elevated risk, although Mab can also infect otherwise healthy individuals, causing pulmonary and cutaneous disease. Clinical management remains challenging due to intrinsic antibiotic resistance and the limited efficacy of standard anti-tuberculosis regimens. Despite this growing burden, the mechanisms governing Mab persistence and pathogenesis remain poorly defined. Progress has been constrained by the limitations of existing animal models. Mice typically clear infections rapidly, even when immunocompromised, limiting studies of chronic disease. Zebrafish support persistent infection but lack lungs and have a less developed adaptive immune system. These limitations highlight the need for alternative models. Here, we present a perspective highlighting the amphibian Xenopus laevis as a complementary model for investigating Mab chronic infection and disease. X. laevis tadpoles develop functional lungs early and possess conserved innate and adaptive immune components, including macrophages and antigen presentation pathways. Their external development allows precise control of environmental exposures and accessibility to experimentation, such as live imaging, to study Mab infection over 50 days. Xenopus models combine the experimental accessibility of early developmental stages, genetic and transgenic tractability, and established protocols for animal husbandry and mycobacterial that are characteristic of zebrafish, with the conserved lung architecture of mammals. We discuss the application of Xenopus models to investigate the potential role of a novel putative secondary metabolite gene cluster (SMGC) hypothesized to encode a virulence factor that promotes Mab colonization, interaction with macrophages, and persistence. Collectively, these features establish X. laevis tadpoles as a valuable experimental platform for dissecting host–pathogen interactions and for identifying potential targets for therapeutic intervention.

Background/Objectives: Mild traumatic brain injury (mTBI) can cause persistent neuroinflammation and astroglial reactivity. This study examined whether peri-injury administration of stearidonic acid ethanolamide (SDEA) was associated with changes in astrocyte-associated responses after mTBI and in primary astroglial cultures. Methods: Male C57BL/6 mice received SDEA (10 mg/kg, subcutaneously) for 2 days before mTBI, immediately after injury, and for 7 days thereafter. At 11 weeks post-injury, cortical GFAP immunoreactivity and the expression of astrocyte-associated markers, PPAR isoforms, and neurotrophic factors were assessed by immunohistochemistry and RT-qPCR. Primary astroglial cultures were treated with 1 or 10 μM SDEA for 48 h. Results: SDEA attenuated mTBI-associated increases in GFAP-positive cells and cortical Gfap and C3 expression while increasing S100a10 and Clcf1 expression. SDEA treatment was accompanied by increased cortical Ppara and Pparg mRNA expression and changes in the expression of neurotrophic-factor genes. In cultured astroglia, SDEA increased S100a10, Clcf1, Ppara, Pparg, Bdnf, Ngf, and Gdnf mRNA expression without significantly altering Gfap or C3. Conclusions: Peri-injury SDEA administration was associated with reduced chronic cortical GFAP reactivity and changes in selected astrocyte-associated transcripts after mTBI.