Local Cerebral Glucose Metabolism in Rats with Chronic Portacaval Shunts

Abstract

Local cerebral glucose utilization was measured with the autoradiographic [¹⁴C]deoxyglucose method in rats at 2 days and 1, 4, 8, and 12 weeks after the construction of a portacaval shunt, and in weight-matched controls. Local glucose utilization in brain was altered in shunted animals, but the magnitude and direction of the changes differed among 36 neuroanatomical structures, depending upon the length of time that the animals had been shunted. In rats shunted for 4 weeks or less, glucose utilization did not differ from control (30 of 36 structures) or was decreased (6 structures). The largest decreases of glucose utilization, noted at 1 week, occurred in the parietal (– 25%) and frontal cortices (– 28%) and subcortical white matter (– 50%). In rats shunted for 8 weeks, however, glucose utilization was higher than control in many brain structures (13 of 36), and after 12 weeks it was higher than control in most structures (25 of 36). Only the parietal cortex did not follow this trend; it exhibited a decreased rate of glucose utilization in rats shunted for 8 weeks (–21%) that normalized in animals shunted for 12 weeks. Portal-systemic shunting of blood increased arterial blood ammonia concentrations to twice the control value of 85 ± 3 μ M in animals shunted for 1 week, and to ∼2.5 times control in animals shunted for 4–12 weeks. Kety-Schmidt measurements of cerebral blood flow and arterial–venous (torcular) differences for ammonia across the brains of control rats and rats with portacaval shunts for 8 weeks revealed an increased cerebral uptake of ammonia in the shunted animals. The late-developing morphological changes known to occur in astrocytes and the delayed increases in local glucose consumption in rats with portacaval shunts may be related, and represent an adaptive response to sustained hyperammonemia.