Effects of phenobarbital on cerebral blood flow and metabolism in young and aged rats

Abstract

The cerebrovascular and cerebral metabolic changes produced by intraperitoneal injection of phenobarbital (50, 150, and 250 mg/kg) were studied in young adult (6-month) and senescent (28-month) Wistar rats. Cerebral blood flow (CBF) was measured using radioactive microspheres and cerebral oxygen consumption (CMR(O2)) was obtained by multiplying cortex CBF by the arterial-sagittal sinus oxygen content difference. Control values for blood pressure, blood gas tensions, CBF, and CMR(O2) were similar in the young and aged animals during 70% N2O/30% O2. Intraperitoneal phenobarbital produced dose-dependent decreases in CBF with no significant difference between young and aged rats at each phenobarbital dose. At the highest phenobarbital dose (250 mg/kg) CBF was reduced by 49% in the young rats and 52% in the aged rats (P > 0.10). CMR(O2) was also depressed in a dose-dependent fashion in both young and aged animals with each phenobarbital dose. However, the decrease produced by the highest phenobarbital dose was significantly greater in the aged rats (55%) than the young rats (43%, P < 0.05), even though the EEG was isoelectric in both groups. The difference in CMR(O2) between young versus aged rats at a time when the EEG is isoelectric suggests that high-dose phenobarbital may depress nonelectrical cerebral metabolic processes more in aged rats.