Spatial, temporal and functional analysis of brain damage after microembolization

The mammalian brain depends on a well-controlled delivery of nutrients and oxygen in order to function properly. These components reach the brain via the blood circulation through a network of cerebral arteries, arterioles and capillaries. Obstructions of the cerebral vasculature can cause disturbance of homeostasis and lead to severe neurological deficits. In this thesis we evaluated the spatiotemporal effects of multiple occlusions at the arteriole level on brain tissue and investigated intrinsic mechanisms of blood flow restoration and debris clearance.
Chapter 1 forms an introduction to the thesis. In chapter 2 the impact of occlusions on brain tissue perfusion and oxygenation is studied by using both in vivo and in silico approaches. In chapter 3, we studied the spatial relationship between occlusion site and the induced hypoxic or infarcted regions. In chapter 4 we monitored and quantified brain lesions in terms of ischemia, hypoxia and infarction for a period of seven days. Possible recovery mechanisms were investigated in the following chapters. Chapter 5 focuses on the blood brain barrier (BBB) disruption, a severe complication of (micro-) occlusions and on the mechanisms that restore homeostasis. In chapter 6, we studied angiophagy, the extravasation of microspheres to the brain parenchyma, using both in-vitro and in-vivo experiments. Since microemboli are actively transferred to the brain parenchyma through angiophagy, we investigated in chapter 7 whether this mechanism can be exploited for the transfer of therapeutic compounds through the BBB. Finally, the findings of this thesis, future perspectives and conclusions are presented in chapter 8.