Abstract: Beyond immediate neuronal damage, functional and structural connectivity is altered brain-wide with implications for functional deficits and recovery in stroke. It remains unclear, however, if the level of axonal damage, as well as compensatory plasticity, i.e., axonal sprouting and remyelination, depend on the lesion size and topology. This study compared two different stroke models in adult male mice, with the aim of uncovering the dynamics in white matter changes. Repetitive diffusion magnetic resonance imaging was acquired over 4 weeks post photothrombotic cortical (1.41% ± 0.92% of brain volume) and middle cerebral artery occlusion cortico-striatal (11.53% ± 2.8% of brain volume) strokes. Structural connectivity changes were mapped over time at the whole-brain level. We quantified inter- and intra-hemispheric seed strength changes over time, with seed strength reflecting how strongly each region was connected to the rest of the brain. Differences between groups and time points were assessed using a mixed model corrected for multiple comparisons. The results showed that large cortico-striatal lesions led to increased structural connectivity in sensorimotor regions, whereas small cortical lesions induced asymmetric connectivity changes: an increase extending globally from the ischemic hemisphere and a decrease expanding globally from the healthy hemisphere. These findings highlight that stroke severity and lesion size significantly affect the temporal dynamics and spatial distribution of connectivity disruptions, emphasizing the need for targeted monitoring of neural changes post-stroke.

Key words: brain network, degeneration, diffusion MRI, fiber tracking, longitudinal, middle cerebral artery occlusion, mouse, photothrombosis, rodent, white matter plasticity