Signal Transduction and Gene Regulation in Cerebral Arteries Following Ischemia

Sammanfattning: The thesis consideres the molecular events that take place in the cerebral arteries following a stroke. The degree and temporal course of reperfusion following a stroke is pivotal for the survival of the neuronal tissue in the penumbra. Previous investigations have revealed upregulation of contractile receptors, a putative factor in the blood flow reduction following stroke that can could augment cell death. The major aim of the study is achieve a better understanding of the changes that occur in the cerebral arteries following a stroke and of the resulting activation of the signal pathways involved, along with changes in gene expression and protein regulation to further the knowledge of how arteries participate in the events that take place following a stroke. The more specific goals have been the following: ' To investigate the gene regulation in cerebral arteries following SAH, aimed at determining what the important processes involved in the increase in contraction are. ' Investigation of MAPK activation and its relation to gene expression. ' Comparison of the ischemic models MCAO and SAH with organ culture of cerebral arteries to determine similarities and to validate the use of organ culture as a model. ' Investigation of gene expression and protein regulation in human MCA following thromboembolic stroke so as validate previous findings in connection with experimental rat models. ' Molecular characterization of smoke induced changes in cerebral arteries.