Objective In the bone-enclosed CNS, increased vascular permeability may cause life-threatening tissue swelling, and/or ischemia and inflammation which compromise tissue repair after trauma or stroke. The brain vasculature possesses several unique features collectively named the blood-brain barrier (BBB) in which passive permeability is almost completely abolished and replaced by a complex of specific transport mechanisms. The BBB is necessary to uphold the specific milieu necessary for neuronal function. Whereas breakdown of the BBB is part of many CNS diseases, including stroke, neuroinflammation, trauma and neurodegenerative disorders, its molecular mechanisms and consequences are unclear and debated. Conversely, the intact BBB is a huge obstacle for drug delivery to the brain. Research on the BBB therefore has two seemingly opposing aims: 1) to seal a damaged BBB and protect the brain from toxic blood products, and 2) to open the BBB “on demand” for drug delivery. A major problem in the BBB field has been the lack of in vivo animal models for molecular and functional studies. So far, available in vitro models are not recapitulating the in vivo BBB. Our recent work on mouse models lacking pericytes, a BBB-associated cell type, demonstrates a specific role for pericytes in the development and regulation of the mammalian BBB. These animal models are the first ones showing a general and significant BBB impairment in adulthood, and as such they provide a unique opportunity to address molecular mechanisms of BBB disruption in disease and in drug transport across the BBB. Importantly, the new models and tools that we have developed allow us to search for relevant druggable mechanisms and molecular targets in the BBB. The long-term goals of this proposal are to develop molecular strategies and tools to open and close the BBB “on demand” for drug delivery to the CNS, and to explore the importance and mechanisms of BBB dysfunction in neurodegenerative diseases and stroke. Fields of science medical and health sciencesbasic medicineneurologystroke Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Call for proposal ERC-2011-ADG_20110310 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution UPPSALA UNIVERSITET EU contribution € 2 435 327,00 Address VON KRAEMERS ALLE 4 751 05 Uppsala Sweden See on map Region Östra Sverige Östra Mellansverige Uppsala län Activity type Higher or Secondary Education Establishments Administrative Contact Birgitta Gustafsson (Mrs.) Principal investigator Björn Christer Betsholtz (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all UPPSALA UNIVERSITET Sweden EU contribution € 2 435 327,00 Address VON KRAEMERS ALLE 4 751 05 Uppsala See on map Region Östra Sverige Östra Mellansverige Uppsala län Activity type Higher or Secondary Education Establishments Administrative Contact Birgitta Gustafsson (Mrs.) Principal investigator Björn Christer Betsholtz (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data KAROLINSKA INSTITUTET Participation ended Sweden EU contribution € 64 100,00 Address Nobels Vag 5 17177 Stockholm See on map Region Östra Sverige Stockholm Stockholms län Activity type Higher or Secondary Education Establishments Administrative Contact Jill Blomstrand Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
