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Hoehn, M.

Publications and source records attributed to Hoehn, M..

3 recordsLinked to original sources

Structure-function coupling reveals hemisphere-specific network reorganization after stroke

MRI is an excellent tool for monitoring functional and structural network reorganization after brain injury and may provide biomarkers for treatment stratification and novel neuromodulatory interventions. In ischemic stroke, functional network changes, particularly within the contralesional hemisphere, and structural integrity, most prominently of the corticospinal tract, have been successfully associated with behavioral deficit and outcome. However, these components are commonly studied separately and at single time points, which does not reflect the highly dynamic nature of brain network plasticity. Here, we characterized structural and functional connectivity (SC-FC) coupling in the healthy mouse brain and longitudinally assessed intra- and inter-hemispheric connections up to 4 weeks after cortical and cortico-striatal stroke. In the healthy brain, intra-hemispheric SC-FC coupling was lateralized in the sensorimotor network (SMN), whereas the default mode network (DMN) showed no significant hemispheric difference. Intra-hemispheric coupling exceeded inter-hemispheric coupling in the SMN. After cortical stroke, regions with high baseline intra-hemispheric SC-FC coupling remained largely stable, whereas initially weakly coupled sensorimotor regions showed delayed increases within the ischemic hemisphere. Contralesional intra-hemispheric SC-FC coupling changed little, but directional inter-hemispheric analyses revealed selective remodeling, including increased contralesional-to-ischemic coupling of primary motor cortex and reduced bidirectional coupling of medial sensorimotor cortex. Cortico-striatal stroke produced fewer longitudinal changes, dominated by reduced inter-hemispheric motor-cortex coupling. These alterations did not simply correspond to regional lesion involvement. Thus, hemisphere- and direction-resolved SC-FC coupling uncovers network- and stroke-model-specific reorganization not detectable when structural and functional connectivity are analyzed independently.

neuroscience↗

Dynamic structural connectivity changes in cortical and cortico-striatal strokes in mice

Stroke is a primary global health concern, leading to significant mortality and long-term disability. Beyond immediate neuronal damage, functional and structural connectivity is altered brain-wide with implications for functional deficits and recovery. It remains unclear, however, if the level of degeneration, i.e. reduced myelination and axonal damage, as well as compensatory plasticity, i.e., axonal sprouting and remyelination, depend on the lesion size and topology. This study compares for the first time two different stroke models in adult male mice, with the aim of uncovering the dynamics in white matter changes. Repetitive diffusion magnetic resonance imaging (dMRI) over four weeks post photothrombotic cortical (1.41{+/-}0.92% of brain volume), and middle cerebral artery occlusion (MCAO) cortico-striatal (11.53{+/-}2.8% of brain volume), strokes were used to map structural connectivity changes at the whole-brain level. We quantified inter- and intra-hemispheric seed strength changes over time, with seed strength reflecting how strongly each region is connected to the rest of the brain. Differences between groups and time points were assessed using a mixed model corrected for multiple comparisons. In conclusion, 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. Significance statementPathophysiological changes close to an ischemic lesion are well understood. But structurally connected regions also undergo stroke-related changes potentially contributing to functional deficits. Animal studies using in vivo diffusion MRI to quantify white matter changes have been limited to single connections, time points after stroke, and basic diffusion measures. We provide the first in-depth characterization of whole-brain fiber tracking to compare small cortical and large cortico-striatal strokes. We found a complex dynamic of decreasing and increasing structural connectivity in single sensorimotor-related brain regions within the brain network - even remote areas from the stroke lesion. This study provides a better understanding of the interactions of regions during stroke recovery, which may help in developing therapies targeting localized white matter repair.

neuroscience↗

Reactive astrocytes prevent maladaptive plasticity after ischemic stroke

Restoration of functional connectivity is a major contributor to functional recovery after stroke. We investigated the role of reactive astrocytes in functional connectivity and recovery after photothrombotic stroke in mice with attenuated reactive gliosis (GFAP-/-Vim-/-). Infarct volume and longitudinal functional connectivity changes were determined by in vivo T2-weighted MRI and resting-state functional MRI. Sensorimotor function was assessed with behavioral tests, and glial and neural plasticity responses were quantified in the peri-infarct region. Four weeks after stroke, GFAP-/-Vim-/- mice showed impaired recovery of sensorimotor function and aberrant restoration of global neuronal connectivity. These mice also exhibited maladaptive plasticity responses, shown by higher number of lost and newly formed functional connections between primary and secondary targets of cortical stroke regions and increased peri-infarct expression of the axonal plasticity marker Gap43. We conclude that reactive astrocytes are required for optimal recovery-promoting plasticity responses after ischemic stroke.

neuroscience↗