Prostanoids attenuate pial arteriolar dilation induced by cortical spreading depression in rabbits

The role of prostanoids in mediating cerebrovascular responses to cortical spreading depression (CSD) was examined in anesthetized rabbits. CSD was elicited by KCl microinjection, and its propagation was monitored electrophysiologically. Pial arterial diameter was determined using a closed cranial window and intravital microscopy, and regional cerebral blood flow (rCBF) was determined using laser flowmetry. Levels of peri-arachnoid cerebrospinal fluid prostanoids were determined by radioimmunoassay. CSF increased pial arteriolar diameter 62% and rCBF 354% over the baseline levels. Locations of propagating CSD, dilating pial arteriole, and increased rCBF were always closely associated spatiotemporally. Cerebrospinal fluid prostanoid levels increased during single CSD-induced arteriolar dilation, and they were further augmented during multiple CSDs. Indomethacin enhanced both CSD-induced vasodilation (88%) and rCBF increase (580%), but it decreased the cerebrospinal fluid levels of prostanoids below the baseline levels and prevented their increase during CSD-induced vasodilation. These results indicate that prostanoids are synthesized from neurons or glial cells and/or the brain vessels and, as the net result, counteract pial arteriolar dilation and rCBF increase during CSD. In addition, they support the hypothesis that the vasodilation is caused primarily by neurogenic factors associated with CSD.