Characterization of vascular affection and blood-brain barrier breakdown following focal cerebral ischemia
funded by (Europäischer Sozialfonds)
In the setting of stroke, ischemia clinically not only affects the neuronal function of patients concerned, but also the function of the cerebral vasculature. Here, a loss of the blood-brain barrier (BBB) function of affected vessels contributes to an ischemia-related brain edema, which critically impacts on the clinical outcome. In this context, we are aiming to characterize the patterns of ischemia-related BBB breakdown using different and translationally relevant models of experimentally induced focal cerebral ischemia and reperfusion at different time points after ischemia induction. Thereby we are able to determine the time course and the extent of the associated BBB breakdown in vessels showing an increased permeability using light-, fluorescence- and electron microscopy. In this context, we were able to demonstrate severe degenerations in vessels showing loss of BBB integrity, which not only involve the endothelial layer, but also the vascular wall. Of note, distinct stages of vascular affection were identified in different sections of the vascular tree, which can be used to evaluate and compare the integrity of the cerebral vasculature at different time points and in different regions of the affected brain parenchyma. Further, our data highlights the significance of the endothelial and vascular integrity for the development of an ischemia-related brain edema. Thus, protection of endothelial cells is likely to represent a promising target for additional neuroprotective strategies.