Dose-response effects of acute ethanol infusions were studied, noninvasively, in the unopened brain to examine the hypothesis that ethanol can induce stroke-like events as a consequence of cerebral vasospasm and tissue ischemia. By using a single sending and receiving fiber, an optical backscatter measurement (500-800 nm) was used to monitor the levels of deoxyhemoglobin (DH), reduced cytochrome oxidase (rCO), and relative tissue blood content in a closed cranium preparation. Anesthetized rats were prepared by cannulating a branch of the internal carotid artery and subjected to either bolus infusions (1.25 or 2.5 mu M ethanol in Ringers/g tissue) or to constant infusions of 5 or 10% ethanol at various rates (0.30-2.92 mu M/g/min). To facilitate optical penetration, a portion of the left parietal cranium was shaved to a translucent appearance. Results showed that low, bolus doses of ethanol typically produced a slight increase (5-10%) in the oxyhemoglobin signal, indicating that vasodilation had probably occurred. Higher doses, however, produced a prompt and significant reduction in the hemoglobin signal, increased levers of DH, and a rise in rCO suggesting a vasoconstrictor response leading to ischemia had occurred, followed by recovery within 3-5 min. Constant infusions of ethanol produced a similar cerebral vascular response, in a dose-related manner, but of a more sustained nature. At levels of 50-60% of the maximum bolus dose, the effect was more pronounced, accompanied by an increase in the levels of rCO (by 50-90%). Control experiments using identical volumes/flow rates of Ringers solution produced no significant alterations in the optical spectrum. Overall, these data indicate that, depending on dose: (a) ethanol can induce vasodilatory or vasoconstricter effects in the intact brain; (b) the more pronounced effects involve vasospasm in the cortical microcirculation leading to global ischemia; and (c) optical measurements permit direct noninvasive assessment of the cerebral vascular effects of alcohol and, potentially, other substances of abuse.
