Microcirculation and Plasticity After Stroke

The Interplay of Microcirculation and Plasticity After Ischemic Stroke

Reperfusion is the main goal of early medical interventions after stroke, such as thrombolysis and thrombectomy. Recanalization works only if applied early - the earlier the better, but with a statistical cutoff of 4.5 hours where risk of hemorrhage outweighs the benefit. Recently, this cutoff has been put into perspective using standardized perfusion measurements by magnetic resonance imaging (MRI) or computed tomography (CT). Two trials have shown that revascularization is beneficial up to 24 hours after stroke onset if patient selection is based on perfusion imaging. This suggests interindividual differences in the temporal evolution of an infarction. One explanation for interindividual differences is the variability of the collateral blood supply to the brain, which in turn can maintain different perfusion pressures around the infarct core, also called the penumbra region. Insufficient recruitment of these collateral pathways is an independent negative predictor of poor outcome; the insufficiency may in part be explained by insufficient dilatation of arterioles ("low dilator reserve"). So far, interventions to improve collateral perfusion, e.g., induced hypertension, have not demonstrated effectiveness, likely because our understanding of collateral perfusion, demand-dependent dilatation of arteries (cerebrovascular reserve, CVR) and their effect on microcirculation is insufficient. Functional recovery after a brain lesion is based on plasticity. Plasticity involves the creation of new synapses, fibers (axons and dendrites) and lasting modification to synaptic strength as well as the formation and migration of new neurons. In the cortex surrounding an infarct, plasticity is facilitated by ischemia via modification of gene expression, i.e. a certain time window after stroke, and is stimulated by activity and training. Tissue microcirculatory status and perfusion surrounding the stroke lesion may play a role in the formation of this plasticity. The investigators will analyze the contributions of pre-existing vascular networks, the impact of stroke-affected vessels, timing and degree of recanalization success, brain excitability, and short-term intra-cortical inhibition to better understand how these factors relate to functional recovery after stroke.

Microcirculation and Plasticity After Stroke

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