Stroke, Ischemic Clinical Trial
Official title:
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.
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