Corticospinal Tract Alterations After Ankle Sprain In Adolescence: Unveiling New Insights With The Mouse Model

Lateral ankle sprains (LAS) are associated with corticospinal pathway deficits, and experiencing ankle sprains at a younger age might predispose individuals to more pronounced maladaptive neuroplastic changes in CST compared to their older counterparts. However, existing evidence is primarily based on cross-sectional investigations and noncausal speculations. PURPOSE:To determine whether maladaptive corticospinal pathway alterations occur pre- and postligament transection in LAS mouse models, and explore whether the alterations are more pronounced in adolescent mice than in adults. METHODS:Twenty-four 8-week-old adolescent and twenty-four 24-week-old adult mice were randomly assigned to lateral ankle ligament transection or sham surgery. Diffusion-weighted imaging of the corticospinal pathway was performed presurgery and 8 weeks postsurgery. Fractional anisotropy (FA) values, reflecting fiber integrity within the corticospinal subregions of the medulla, pons, midbrain, and cerebrum, were extracted. RESULTS:Repeated measurements of image acquisition were conducted on 41 mice. Two months after surgery, the FA of the medulla subregion of mice in the adolescent cohort increased from 0.873 ± 0.044 to 0.967 ± 0.053 in the control group (p<0.05). In contrast, the adolescent cohort of LAS group demonstrated a decline from 0.901 ± 0.061 to 0.809 ± 0.072 (p<0.05), revealing a statistically significant effect once the baseline was adjusted (β = −0.083, 95% CI: −0.145 to −0.021, P-FDR = 0.048). Significant LAS surgery effects on the FA of corticospinal outcomes were neither noted in the adult experiment nor observed in other DWI outcomes (Figure). CONCLUSIONS:The central nervous system exhibits maladaptive corticospinal responses in the adolescent LAS mouse model, characterized by reduced fiber integrity in the medulla subregion.