In the setting of ischemic stroke, loss of blood-brain barrier (BBB) function contributes to an ischemia-related brain edema, which detrimentally impacts on the clinical outcome of concerned patients. In this setting, we are aiming to characterize the patterns and the time course of ischemia-related BBB breakdown using different and translationally relevant models of experimentally induced focal cerebral ischemia and reperfusion. Using light-, fluorescence- and electron microscopy, we were able to demonstrate severe vascular degenerations in areas of impaired 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. Therefore, 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 supportive neuroprotective strategies.
Krueger M, Härtig W, Frydrychowicz C, Mueller W, Reichenbach A, Bechmann I, Michalski D (2017) Stroke-induced blood-brain barrier breakdown along the vascular tree - No preferential affection of arteries in different animal models and in humans. J Cereb Blood Flow Metab. 37(7):2539-2554.
Hanske S, Dyrna F, Bechmann I, Krueger M (2017) Different segments of the cerebral vasculature reveal specific endothelial specifications, while tight junction proteins appear equally distributed. Brain Struct Funct. 222(3):1179-1192.
Krueger M, Bechmann I, Immig K, Reichenbach A, Härtig W, Michalski D (2015) Blood-brain barrier breakdown involves four distinct stages of vascular damage in various models of experimental focal cerebral ischemia. J Cereb Blood Flow Metab. 35(2): 292-303
Krueger M, Härtig W, Reichenbach A, Bechmann I, Michalski D (2013) Blood-Brain Barrier Breakdown after Embolic Stroke in Rats Occurs without Ultrastructural Evidence for Disrupting Tight Junctions. PLoS One 8(2):e56419.
Krueger M, Mages B, Hobusch C, Michalski D (2019) Endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia. Acta Neuropathologica Communications 7:17.
Mages B, Aleithe S, Blietz A, Krueger M, Härtig W, Michalski D (2019) Simultaneous alterations of oligodendrocyte-specific CNP, astocyte-specific AQP4 and NF-L demarcate ischemic tissue after experimental stroke in mice. Neurosci Lett. 711, 134405
Mages B, Aleithe S, Altmann S, Blietz A, Nitzsche B, Barthel H, Horn AK, Hobusch C, Härtig W, Krueger M & Michalski D (2018) Impaired neurofilament integrity and neuronal morphology in different models of focal cerebral ischemia and human stroke tissue. Front Cell Neurosci. 12:161.doi:10.3389/fncel.2018.00161