Ritanserin, a 5-HT2 receptor antagonist, increases subcortical blood flow following photothrombotic middle cerebral artery occlusion in rats

It has been proposed that the reversal of serotonin-mediated vasoconstriction accounts for the neuroprotective effect of serotonin (5-HT2) receptor blockade in local cerebral ischemia. We investigated the effect of pretreatment with ritanserin, a 5-HT2 receptor antagonist, on cerebral blood flow in a model of photothrombotic middle cerebral artery occlusion in rats. Local cerebral blood flow was measured by iodoantipyrine autoradiography 30 minutes after induction of ischemia. Using a novel image-alignment algorithm, 3-dimensional reconstructions of averaged cerebral blood flow were calculated. The difference-image of local cerebral blood flow between ritanserin and vehicle-treated animals revealed a subcortical zone underlying the ischemic cortex where cerebral blood now was markedly enhanced indicating a beneficial hemodynamic effect of ritanserin. Three-dimensional image analysis provides a powerful tool to detect inter-group differences of cerebral blood flow which are underestimated by conventional types of data analysis.