MICROFLOW · Molecular mechanisms of microvascular dysfunction following hemorrhagic stroke

Molecular mechanisms of microvascular dysfunction following hemorrhagic stroke

Subarachnoid hemorrhage (SAH) is a stroke subtype associated with a 50% mortality and a particularly unfavorable functional outcome. One of the main factors contributing to the pathogenesis of SAH-induced brain damage is cerebral ischemia. The current project aims to investigate the role of cerebral microvessels for post-hemorrhage ischemia and identify the involved cellular and molecular mechanisms thereby helping the applicant to move his laboratory from the Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland, to the Institute for Stroke and Dementia Research (ISD) at the University of Munich. With the help of the current funding the applicant managed to set up his laboratory at the Institute for Stroke and Dementia Research in Munich and to start and maintain an internationally competitive research program in the field of ischemic and hemorrhagic stroke research and to expand his research activities on the cerebral microcirculation to vascular dementia and traumatic brain injury. He acquired over 1.8 million Euros in additional funding from various national (German Excellence Initiative, German Research Foundation), international (Era-Net Neuron, coordinator; ITN EVOluTION), and private (Else-Kröner-Fresenius Foundation, Bayer Post-doc Program) funding organizations, formed a well working research group of meanwhile 22 dedicated and talented scientists, and managed to publish 39 research papers on the pathogenesis of secondary brain injury since the beginning of the project. Regarding the specific aims of the current project the applicant helped the Institute for Stroke and Dementia Research to establish a state-of-the art animal facility for in vivo research, transferred in vivo models for the investigation of SAH, ischemic stroke, and traumatic brain injury to Munich, and set-up an in vivo brain imaging laboratory allowing for the investigation of cerebral microvessels in the living brain. Using this infrastructure the applicant's laboratory further characterized the constriction of pial microvessels after SAH ("microvasospasms"), showed that these constrictions result in a massive, wide-spread and long-lasting perfusion deficit of the intraparenchymal microcirculation, demonstrated that pial as well as intraparenchymal arterioles and capillaries show a complete loss of carbondioxide-induced vasodilatation, and recently proved that following SAH neuro-vascular coupling is severely impaired, that is that neuronal activity instead of dilating cerebral vessels results in vasoconstriction. These findings demonstrate that cerebral microvessels suffer from severe dysfunction after SAH. In summary, the current grant helped the applicant tremendously to transfer his laboratory from Ireland to Germany, to reintegrate into the German research system, to help the host institute to build up state-of-the-art infrastructure for in vivo research, to acquire significant additional national and international funding, to establish an internationally competitive research group with currently about 20 members, and to publish almost 40 scientific papers since the initiation of funding. Prof. Dr. Nikolaus Plesnila Laboratory of Experimental Stroke Research Institute of Stroke and Dementia Research (ISD) University of Munich Medical Center Feodor-Lynen-Straße 17, D-81377 Munich, Germany Tel.: +49 89 4400 46 219 or 220 Email: nikolaus.plesnila@med.uni-muenchen.de Internet: www.isd-muc.de

Data: CORDIS, © European Union