Peripheral nerve injuries often lead to long-term functional deficits due to limited intrinsic regeneration and secondary inflammatory and oxidative damage. This study evaluated the therapeutic efficacy of M2 macrophage-derived exosomes (M2-Exosomes), hyperbaric oxygen therapy (HBO), and their combined administration in a rat model of sciatic nerve crush injury. Animals were randomly divided into five groups: sham, control (injury without treatment), exosome, HBO, and Exosome+HBO. HBO was administered in a pressurized chamber, while exosomes were injected immediately post-injury and at scheduled intervals. Functional recovery was assessed longitudinally using the Sciatic Functional Index (SFI). Electrophysiological analyses, including electromyography (EMG) latency, histological and morphometric evaluations, inflammatory cytokine quantification (tumor necrosis factor-α TNF-α, interleukin-1β IL-1β, and interferon-γ IFN-γ), and oxidative stress biomarkers (glutathione GSH, superoxide dismutase SOD, catalase CAT, and malondialdehyde MDA) were measured at defined endpoints. The Exosome+HBO group demonstrated the most rapid and substantial improvement in SFI values across the 28-day assessment period, outperforming both monotherapies. Electrophysiological evaluation showed significantly reduced EMG latency in all treatment groups relative to controls, with latency in the combined-therapy group approaching near-sham values. Histological analysis demonstrated superior axonal density, fascicular organization, and nerve volume in the combined-treatment group, consistent with enhanced structural regeneration. Inflammatory cytokines were markedly attenuated by both therapies but exhibited the greatest reduction under dual treatment. Similarly, oxidative stress parameters showed the most pronounced antioxidant restoration and MDA reduction in the Exosome+HBO group. In conclusion, M2-Exosomes and HBO independently promote functional and structural recovery after sciatic nerve crush injury, and their combined administration produces enhanced improvements across neurofunctional, biochemical, and histological parameters, highlighting this strategy as a promising therapeutic approach for peripheral nerve repair.
Abdullah A. Alqasem (Wed,) studied this question.