EVIDENCE AGAINST PARENCHYMAL METABOLITES DIRECTLY PROMOTING PIAL ARTERIOLAR DILATION DURING CORTICAL SPREADING DEPRESSION IN RABBITS

The role of parenchymal metabolic factors in directly promoting pial arteriolar dilation during cortical spreading depression (CSD) in anesthetized rabbits was examined by direct measurement of periarachnoid cerebrospinal fluid (CSF) levels of a representative metabolite (i.e., K+) or superfusion of the cerebral cortical surface with artificial CSF. CSD was induced by KCl microinjection or tissue puncture and its movement was monitored electrophysiologically. Pial arteriolar diameter was determined using a closed cranial window and intravital microscopy. CSD propagated across the cortex under the window with a velocity of 2.9 +/- 0.2 mm/min, and caused pial arteriolar diameter to increase from 87 +/- 9-mu-m to 133 +/- 11-mu-m (53%, n = 23) for 1.6 +/- 0.1 min. At the same time, K+ concentration increased from 3.0 +/- 0.2 mM to a maximum of 4.6 +/- 0.3 mM. Topical application of 6 mM K+ increased pial arteriolar diameter by only 8%. Continuous superfusion of the cortical surface with aCSF at a rate of 3.0-4.5 ml/min (window volume = 0.5 ml) did not affect pial arteriolar dilation during CSD, but virtually abolished pial arteriolar dilation during inhalation of 10.2% CO2. These results suggest that pial arterioles dilate via a mechanism which does not involve diffusion of vasoactive metabolites released from the parenchyma during CSD.