Title:

"Brain Microcirculation and Tissue Damage after Subarachnoid Hemorrhage"

English Summary:

The poor outcome after subarachnoid hemorrhage (SAH) is mainly ascribed to delayed cerebral ischemia (DCI), which is traditionally believed to be the result of parallel vasospasms. This causal relation has recently been questioned and the capillary bed flow was proposed as a crucial contributor to the brain damage after SAH. In the current PhD project, we investigated the role of microcirculation in ischemic brain injury four days after SAH in mice and estimated tissue oxygenation based on capillary flow pattern changes. Tissue injury was addressed by volumetric investigation of the hippocampus as well as astrocytic morphological changes and capillary coverage by astrocyte endfeet. Microvascular changes and tissue hypoxia may render brain tissue vulnerable to some injuries that are known to occur in the aftermath of SAH. One such injury mechanism, cortical spreading depolarization (CSD), imposes extreme metabolic demands on brain tissue. We determined the temporal dynamics of arteriolar diameter and capillary perfusion in relation to the arrival of the CSD waves and tried to address whether capillaries or arterioles are first affected by CSD-related hemodynamic changes.

Overall, the findings of the current PhD project support the notion that capillary flow pattern plays a crucial role in the tissue injury after SAH, where capillary flow disturbance is a primary phenomenon relative to upstream arteriolar constriction. Adding to known sources of capillary dysfunction after SAH, we identified changes in astrocyte morphology and parallel loss of capillary coverage by astrocyte. The observed hippocampal atrophy may provide insights into the etiology of cognitive dysfunction often affecting SAH survivors.

Opponents and Chairman of the Evaluation Committee:

• Associate Professor Vladimir Matchkov (chairman and moderator of the defense)
  Institute of Biomedicine, Aarhus University 
   
• Professor Rick Dijkhuizen
  Biomedical MR Imaging, University Medical Center Utrecht, The Netherlands
   
• Associate Professor, Consultant Neurosurgeon Angelika Gabriele Sorteberg
  Neurovascular Research Group, Dept. Neurosurgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway
   
• Professor, Consultant Leif Østergaard (main supervisor and non-voting member)
  Department of Clinical Medicine, Center of Functionally Integrative Neuroscience, Aarhus University Hospital / Aarhus University

ALL ARE WELCOME