Vascular heterogeneity

The Blood-Brain-Barrier (BBB) is an important feature of blood vessels to protect the central nervous system (CNS) from toxic or possible harmful substances circulating in the bloodstream. In the circumventricular organs (CVOs) which are small brain areas, located in the midline around the third and fourth ventricle physiologically, there is no vascular BBB established. Although this seems to be contradictory at first, a second look reveals that the CNS has to be in contact with the bloodstream in these specialised brain areas to exchange information between these compartments. Therefore, the CVOs are also called communication points between blood and brain and categorised into sensory and secretory organs according to their physiological function. In the project funded by the German Research Council with in the Research Group FOR2325, we are interested in the molecular mechanisms that regulate the absence of BBB properties within CVO vessels and how modulation of vascular barrier function influences the communication of the brain with the blood, hence with peripheral organs such as the kidney.

DFG FOR2325

Supported by the Deutsche Forschungsgemeinschaft (DFG) research group FOR2325 (2016-2019), “The Neurovascular Interface” LI 911/5-1.

Applications for Master thesis welcome!!

Mobirise

TEAM: Vascular heterogeneity

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Undergraduate students welcome

Regulation of BBB genes in epilepsy

Mesial temporal lobe epilepsy (MTLE) is the most common form of refractory epilepsy, characterized by spontaneous recurrent seizures. Functional impairment of the blood-brain barrier (BBB) has been attributed to contribute to the formation and/or progression of the disease. However, a detailed knowledge of the molecular changes at the BBB and the neurovascular unit (NVU) is currently missing. In the project funded by the government of Hesse (LOEWE-CePTER consortium), aims to characterise in detail the effects of MTLE on brain microvessels and endothelial cells. To characterize BBB properties in MTLE, we will isolate microvessel fragments, of morphologically unaffected cortex and epileptic and sclerotic hippocampus tissue of MTLE patients and compare their transcriptome by next generation sequencing (NGS). To examine the role of identified target genes on the BBB, we will overexpress and silence the genes in the expressing cell type of the NVU. We will further test modified cells for their BBB relevant function in co-cultures and by transendothelial electrical resistance (TEER) measurements in vitro.  

LOEWE-CePTER

Supported by the LOEWE-Centre  CePTER - Center for Personalized Translational Epilepsy Research.

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Elif Fidan, PhD student

Mobirise

TEAM: The BBB in epilepsy

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Elif fidan

PhD student

Vascular ageing

Brain endothelial cells (ECs) of the blood-brain barrier (BBB) maintain brain homeostasis via paracellular tight-junctions and specific transporters such as P-glycoprotein. The BBB is responsible for negligible bioavailability of many neuroprotective drugs. In Alzheimer’s disease (AD): • 80% of cases display cerebral amyloid angiopathy (CAA). • CAA present deposition of amyloid-β (Aβ) at the blood vessels. • The source of perivascular Aβ however is not entirely clear, but endothelial expression of the rate-limiting enzyme for Aβ generation, the beta-secretase 1 (BACE-1), suggests a potentially contribution of vessels to CAA formation and AD pathogenesis (Devraj et al., 2016). Moreover, impairment of the BBB even prior to the onset of symptomatic AD has been shown, pointing out the importance of the vasculature in the brain for AD formation and progression. This project was included in the European Training Network H2020-MSCA-ITN-2015, BtRAIN.

BtRAIN (H2020-MSCA-ITN-2015 675619)

Supported by the HORIZON2020 The Marie Skłodowska-Curie actions, Innovative TRaining Natwork - BtRAIN.

Related articles

Moritz Armbrust, MD
Till Janssen, MD student

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Mobirise

TEAM: Vascular ageing

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Moritz Armbrust

MD

Till Janssen

Cand. med.

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