Inhibition of ErbB2 mitigates secondary denervation after traumatic muscle injury

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract Secondary denervation has recently been described as part of the sequela volumetric muscle loss (VML) injury, occurring along with a significantly elevated neurotrophic response, specifically neuregulin‐1 (NRG1). This may contribute to chronic functional impairments associated representing an overlooked treatment target. Thus, though paradoxical, goal this study was pharmacologically reduce signalling after VML using monoclonal antibody (Herceptin) that inhibits ErbB2 receptors. We also assessed whether inhibition combined myogenic (i.e. minced graft) would have synergistically beneficial effect on function. Adult male Lewis rats underwent surgical induction tibialis anterior injury and were randomized into one four groups: untreated, Herceptin, graft + comparisons contralateral (uninjured) control muscle. Rats receiving Herceptin administered drug (8 mg/kg i.p. ) at time surgery thrice per week for duration (48 days). Terminally individual NMJs quantitatively evaluated, maximal in vivo torque tested. fully restored normal rates NMJ innervation morphology improved de novo myofibres muscle‐graft treatment. However did not improve skeletal function alone or combination conclude is promising therapeutic option treating yet more work needed optimize translation characteristics recover image Key points In cases complex traumatic musculoskeletal such (VML), endogenous ability regenerate lost. Innervation, connection motor axon each myofibre, necessary component myofibre survival contractile function, which disrupted VML. Paradoxically monocolonal inhibitor (receptor tyrosine kinase ErbB2; Herceptin) shown regeneration rodent models nerve injury. Here we show pharmaceutical following rat model improves innervation; however it correspondingly Although ineffective its noteworthy should be considered adjunctive combinatorial therapy option.

Language: Английский

Three-Dimensional Analysis of Skeletal Muscle Stem Cell Niche Following Tissue Clearing

Methods in molecular biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский