Diffusion Kurtosis Imaging Evaluates the Neuroprotective Effects of Low-Intensity Treadmill Exercise in a 6-OHDA-Induced Rat Model of Parkinson’s Disease

Abstract Parkinson’s disease (PD) involves progressive degeneration of dopaminergic neurons in the substantia nigra and abnormal accumulation of α-synuclein (αSyn). Low-intensity exercise has shown neuroprotective potential in experimental PD, yet sensitive in vivo methods for tracking associated microstructural changes remain limited. We therefore used diffusion kurtosis imaging (DKI) to evaluate exercise-associated neuroprotection in 6-OHDA-lesioned rats and examined how DKI metrics related to behavioral and pathological measures. Forty rats were randomly allocated to control, sham, PD, and exercise groups. PD lesions were induced by unilateral 6-OHDA injection into the medial forebrain bundle. The exercise group underwent six weeks of low-intensity treadmill training. After the intervention, SN mean diffusivity (MD), fractional anisotropy (FA), and mean kurtosis (MK) were measured using 3.0-T MRI. Motor performance and SN tyrosine hydroxylase (TH) and αSyn immunoreactivity were assessed, followed by correlation analysis. Compared with control animals, PD rats showed decreased FA and MK, reduced TH immunoreactivity, increased αSyn immunoreactivity, and impaired motor performance. Exercise partially attenuated these abnormalities. FA and MK were strongly associated with behavioral and pathological measures, whereas MD showed no significant group differences. Six weeks of low-intensity treadmill exercise partially ameliorated imaging, behavioral, and pathological abnormalities in 6-OHDA-lesioned rats. The data suggest that FA and MK may serve as candidate non-invasive imaging metrics for assessing nigral injury and monitoring exercise-associated treatment responses in this model.