TWO MURDERS AND A CORONATION: CRUSADE, CRISIS, AND THE COUNTS OF FLANDERS, 1071-1204

The medieval counts of Flanders went on crusade with a regularity that was unmatched by the other potentates of Western Europe in the twelfth century. While the comital tradition of crusading has been noted by scholars of the crusades, it has never been carefully studied or explained. This dissertation argues that the tradition of crusading that characterized the medieval counts of Flanders developed as a political and social response to the repeated crises of the eleventh and twelfth centuries. The counts traveled east to Jerusalem in order to solidify and enhance their prestige within the county of Flanders. This tradition began with Robert the Frisian (r. 1071-1093), who made the journey as a pilgrim in 1086 in order to rehabilitate his reputation after a civil war in which he usurped the county by killing his nephew. Robert’s son, Robert II (r. 1093-1111), participated in the First Crusade and was remembered as one of the expedition’s heroes. During and after Robert II’s rule, commemoration of the First Crusade began to create the idea that there was a special connection between the counts of Flanders and crusading. New religious foundations, relics, and books such as Lambert of Saint-Omer’s Liber Floridus each contributed to this idea. This fledgling tradition provided a convenient tool for Thierry of Alsace (r. 1128-1168), who became count in 1128 after a brutal civil war. Thierry consolidated his control over Flanders by going on crusade four times. He also took steps to pass the importance of the comital crusading legacy on to his son, Philip (r. 1168-1191), who went on crusade in part to try to secure his control over Flanders against the incursions of King Philip Augustus of France. The tradition reached its zenith in 1204, when Count Baldwin IX was crowned emperor of Constantinople at the end of the Fourth Crusade. However, in an ironic turn, after going to Jerusalem for more than a century to secure their power in Flanders, the counts lost control of the county almost immediately after their greatest triumph in the East

Volume Regulated Anion Channel Currents of Rat Hippocampal Neurons and Their Contribution to Oxygen-and-Glucose Deprivation Induced Neuronal Death

Volume-regulated anion channels (VRAC) are widely expressed chloride channels that are critical for the cell volume regulation. In the mammalian central nervous system, the physiological expression of neuronal VRAC and its role in cerebral ischemia are issues largely unknown. We show that hypoosmotic medium induce an outwardly rectifying chloride conductance in CA1 pyramidal neurons in rat hippocampal slices. The induced chloride conductance was sensitive to some of the VRAC inhibitors, namely, IAA-94 (300 µM) and NPPB (100 µM), but not to tamoxifen (10 µM). Using oxygen-and-glucose deprivation (OGD) to simulate ischemic conditions in slices, VRAC activation appeared after OGD induced anoxic depolarization (AD) that showed a progressive increase in current amplitude over the period of post-OGD reperfusion. The OGD induced VRAC currents were significantly inhibited by inhibitors for glutamate AMPA (30 µM NBQX) and NMDA (40 µM AP-5) receptors in the OGD solution, supporting the view that induction of AD requires an excessive Na+-loading via these receptors that in turn to activate neuronal VRAC. In the presence of NPPB and DCPIB in the post-OGD reperfusion solution, the OGD induced CA1 pyramidal neuron death, as measured by TO-PRO-3-I staining, was significantly reduced, although DCPIB did not appear to be an effective neuronal VRAC blocker. Altogether, we show that rat hippocampal pyramidal neurons express functional VRAC, and ischemic conditions can initial neuronal VRAC activation that may contribute to ischemic neuronal damage