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Welcome to BRENDA

A Network on Brain Endothelium
funded by the Leducq Foundation


About BRENDA
BRENDA

International Network of Excellence on Brain Endothelium

 A Nexus for Cerebral Small Vessel Disease

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Background

Cerebral small vessel disease (SVD) is a very common progressive vascular disease that covers various pathologies all related to the small vessels in the brain. Due to damage or malfunction of these tiny vessels, the cerebral blood-low is reduced leading to chronic damage of tissue over the years.

SVD is a major cause of microinfarcts and microbleeds—types of stroke that often go undetected, but are major contributors to disability and dementia. Despite such a profound impact on brain health, there are no proven treatments for SVD that can prevent, or slow down the progression of this disease. Treatment is currently limited to reducing common vascular risk factors such as hypertension, diabetes mellitus, hyperlipidemia, and smoking. Additional main risk factors are advanced age and genetic factors.

The underlying pathomechanisms of this disease are still not understood. However, hypertension as the leading risk factor and vascular endothelial dysfunction are clearly associated with cSVD. Brain endothelial cells (BECs) have unique roles at the blood-brain barrier (BBB) and in controlling cerebral blood flow (CBF), including sensing moment-to-moment changes in neural activity. We propose this essential integrator function is progressively degraded in SVD and that microvascular BEC dysfunction serves as a nexus for the loss of brain health.

Yet, we have only scratched the surface in understanding the contribution of BECs to vascular control and brain health. Investigators of this network have identified genetic variants in humans that increase the risk for SVD and stroke. In addition, they have developed mice that express such variants in BECs and have shown that they exhibit SVD and brain injury that mimic those in humans. Our preliminary results suggest that, when combined with genetic variants in BECs, hypertension increases SVD and brain injury to a greater extent than either pathology alone.

Objectives

The BRENDA network aims to investigate the BEC-specific mechanisms underlying SVD, ischemic stroke, and intracerebral hemorrhage. Our overarching hypothesis is that BECs have an initiating role in SVD and that genetic predisposition combined with hypertension synergistically drive SVD (two-hit model). 

Our overall objective is to identify novel pathways and targets for treatment, with the goal of preventing the decline in brain health.

We will combine unique complementary expertise to pursue three highly integrated aims:

Aim 1: Define the mechanisms linking risk genes for SVD & stroke to BEC dysfunction and brain injury.

Aim 2: Test the hypothesis that hypertension synergizes with stroke-risk genes to augment BEC dysfunction and brain injury (“two-hit” model).

Aim 3: Unveil the contribution of BEC heterogeneity to vascular function and brain health.

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BRENDA

The Network

The interdisciplinary network brings together seven basic researchers and clinician scientists with expertise in genetics, cell biology, electrophysiology, RNA seq, optical imaging and stem cell biology. The team is complemented by postdoctoral fellows and graduate students in each lab.

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Coordinators

Martin Dichgans

LMU Hospital, Germany

Frank FARACI

University of Iowa, USA

Members

Anne Joutel

INSERM, France

Mark Nelson

University of Vermont, USA

Elizabeth Hillmann

Columbia University, USA

Christer Betsholtz

Uppsala University, Sweden

Dominik Paquet

LMU Hospital, Germany 

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BRENDA

News

Network News, Events & Open Positions 

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Virtual Seminar Series
February 6, 2024

Nicolas Renier co-developed methods to map the brain and other organs in 3D using tissue clearing and light sheet microscopy . His is interested in the development and plasticity of neuronal and vascular networks.

Guest speaker:

Nicolas Renier

Team leader, Paris Brain Institute

Title: tbd

Virtual Seminar Series
January 9, 2024

Serge Charpak and his team aims to develop new imaging tools that allow investigating brain activity at cellular level. In particular he is interested in the modulation of brain network activity between neurons and non-neuronal cells.

Guest speaker:

Serge Charpak

Professor, INSERM, Paris

Title: tbd

Virtual Seminar Series
December 5, 2023

Edith Hamel is interested in neuronal control of local cerebral blood flow and how this relationship is altered in pathologies like Alzheimer’s disease and vascular cognitive impairment and dementia.

Guest speaker: 

Edith Hamel 

Professor Emerita, Mc Gill University, Montreal, Canada

“Resting-state functional connectivity and neurovascular coupling in Alzheimer’s disease mice through the disease spectrum: Effects of pharmacotherapy.”

Virtual Seminar Series
November 2, 2023 

Andy Shih is an expert in advanced optical imaging to study cerebrovascular disease. He will talk on the regulation of cerebral blood flow through capillaries by pericytes.

Guest speaker: 

Andy Shih 

Associate Professor at Seattle Children’s Research Institute and the University of Washington

"Pericyte roles in maintenance of brain microcirculation during health, aging and small vessel disease"

October 18-20, 2023: 2nd Project Meeting, Munich, Germany

The meeting started with an opening lecture by Fabrice Dabertrand, University of Colorado: “From impaired cerebral blood flow to cognitive impairment“. Following this, the Early Career investigators went downtown for a Munich Experience event.

The following days were filled with stimulating discussion and new ideas for collaborations. The whole team is exicted about the work ahead.

Virtual Seminar Series
September 5, 2023

Martin Lauritzen from University of Copenhagen will be our first guest speaker. 

Martin Lauritzen

Professor
University of Copenhagen

“Brain endothelial cells and the blood-brain barrier”

Virtual Seminar Series – Summer Break
August, 2023

Virtual Seminar Series
July 11, 2023

Rasna Sabharwal, PhD, Assistant Professor in Frank Faraci’s lab and Amreen Mughal, Research Assistant Professor in Mark Nelson’s group will present their work.

Rasna Sabharwal

PhD
University of Iowa

Title: tbd

Amreen Mughal

PhD
University of Vermiont

"Electro-Calcium Coupling and Alzheimer’s disease"

Virtual Seminar Series
June 7, 2023: 

Our new BRENDA Virtual Seminar series that will be held once a month will start in June 2023.The seminars alternate between talks from Early Career Investigators (ECI) and presentations from International Speakers. Louise Schröger, PhD student at Martin Dichgans`s lab is the first ECI who will talk about her ongoing work.

Luise Schröger

PhD student
LMU Hospital Munich, Institute for Stroke and Dementia Research

“Neuronal injury in Foxf2-deficient mice associates with iron overload”

March 26-28, 2023: 1st Project Meeting, New York City, USA

The first in-person meeting was hosted in New York. This was for the first time that senior and junior scientists working in BRENDA came together to getting to know each other and to established new collaborations. 

News Archive

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BRENDA

Publications

latest publications of the BRENDA Network

list of publications

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BRENDA

funded by

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Contact

Prof. Dr. med. Martin Dichgans

Feodor-Lynen-Straße 17

81377 Munich, Germany

Phone: +49 (0)89 4400 46019

Coordinators

Martin Dichgans, Klinikum der Universität München (Germany)

Frank Faraci, The University of Iowa (USA)

Network Administrative Officer:
Karin Waegemann, Klinikum der Universität München (Germany); 

Members

Christer Betsholtz, Uppsala University (Sweden)

Elizabeth Hillman, Columbia University (USA)

Anne Joutel, INSERM Paris (France)

Mark Nelson, The University of Vermont State and Agricultural College (USA)

Dominik Paquet, Hospital of the Ludwig Maximilian Universität München (Germany)

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