MECHANISMS OF EDEMA FORMATION AFTER INTRACEREBRAL HEMORRHAGE - EFFECTS OF THROMBIN ON CEREBRAL BLOOD-FLOW, BLOOD-BRAIN-BARRIER PERMEABILITY, AND CELL-SURVIVAL IN A RAT MODEL

Recently, the authors showed that thrombin contributes to the formatio n of brain edema following intracerebral hemorrhage. The current study examines whether the action of thrombin is due to an effect on cerebr al blood flow (CBF), vasoreactivity, blood-brain barrier (BBB) functio n, or cell viability. In vivo solutions of thrombin were infused stere otactically into the right basal ganglia of rats. The animals were sac rificed 24 hours later; CBF and BBB permeability were measured. The ac tions of thrombin on vasoreactivity were examined in vitro by superfus ing thrombin on cortical brain slices while monitoring microvessel dia meter with videomicroscopy. In separate experiments C6 glioma cells we re exposed to various concentrations of thrombin, and lactate dehydrog enase release, a marker of cell death, was measured. The results indic ate that thrombin induces BBB disruption as well as death of parenchym al cells, whereas CBF and vasoreactivity are not altered. The authors conclude that cell toxicity and BBB disruption by thrombin are trigger ing mechanisms for the edema formation that follows intracerebral hemo rrhage.