Atlas-based analysis of diffusion imaging may predict efficacy of forelimb movement therapy for motor recovery in post-stroke rats.

BACKGROUND

This investigation employed atlas-based analysis of diffusion imaging to elucidate the therapeutic effects of bilateral and unilateral forelimb movement therapy in a rat stroke middle cerebral artery occlusion (MCAO) model.

METHODS

Fifty-six rats were randomized into seven groups: sham, model (moderate/severe), and unilateral-treated (CIMT) (moderate/severe) and bilateraltreated (moderate/severe). Daily forelimb training began on day 7 post-surgery and continued throughout. Brain magnetic resonance imaging (MRI) and catwalk test were conducted on days 6, 14, and 28 post-MCAO. Whole-brain fractional anisotropy (FA) and mean diffusivity (MD) values based atlas evaluated the white matter integrity, complemented by gait analysis to evaluate forelimb motor therapy efficacy in forelimb functional recovery.

RESULTS

Bilateral training showed greater neuroprotection (47-53 % MRI/TTC reduction, p < 0.001) than unilateral (34-24 %)/controls; only unilateral reduced severe infarctions (20-32 %, p < 0.001). Whole-brain DTI in MCAO rats showed injury-dependent white matter reorganization post-movement therapy: Bilateral therapy boosted thalamocortical integrity in moderate injuries (13-32 % FA↑, 8-11 % MD↓, p < 0.05), while unilateral protocol (CIMT) optimized motor pathways in severe cases (6-11 % FA↑, 7-9 % MD↓, p < 0.05). Gait improvements aligned: bilateral enhanced limb contact (+6-7 %) and paw expansion (+20 %, p < 0.05), whereas unilateral accelerated recovery (step cycle↓20-40 %, swing speed↑51-55 %, p < 0.001).

CONCLUSIONS

This study pioneers a diffusion atlas framework combining longitudinal DTI with voxel-wise fixel analysis, to delineate forelimb training-driven white matter reorganization patterns. Bilateral training for moderate impairment maximized structural restoration, while advocating unilateral protocols for severe cases to optimize functional recovery.