Spreading depression (SD) is a slowly propagating wave of transient neuronal and 
glial depolarization that develops after stroke, trauma and subarachnoid 
hemorrhage. In compromised tissue, repetitive SD-like injury depolarizations 
reduce tissue viability by worsening the mismatch between blood flow and 
metabolism. Although the mechanism remains unknown, SDs show delayed 
electrophysiological recovery within the ischemic penumbra. Here, we tested the 
hypothesis that the recovery rate of SD can be varied by modulating tissue 
perfusion pressure and oxygenation. Systemic blood pressure and arterial pO(2) 
were simultaneously manipulated in anesthetized rats under full physiologic 
monitoring. We found that arterial hypotension doubled the SD duration, whereas 
hypertension reduced it by a third compared with normoxic normotensive rats. 
Hyperoxia failed to shorten the prolonged SD durations in hypotensive rats, 
despite restoring tissue pO(2). Indeed, varying arterial pO(2) (40 to 400 mm Hg) 
alone did not significantly influence SD duration, whereas blood pressure (40 to 
160 mm Hg) was inversely related to SD duration in compromised tissue. These 
data suggest that cerebral perfusion pressure is a critical determinant of SD 
duration independent of tissue oxygenation over a wide range of arterial pO(2) 
levels, and that hypotension may be detrimental in stroke and subarachnoid 
hemorrhage, where SD-like injury depolarizations have been observed.