GLYCOGEN, AMMONIA AND RELATED METABOLITES IN THE BRAIN DURING SEIZURES EVOKED BY METHIONINE SULPHOXIMINE¹

Abstract

Abstract— The levels of ATP, P‐creatine, glucose, glycogen, lactate, glutamate and ammonia were measured in mouse brain after administration of the convulsive agent methionine sulphoximine (MSO). No changes were observed in ATP and P‐creatine levels either before or during the seizures. Lactate levels were unchanged until the onset of seizures (4–5 hr) at which time the levels increased an average of 65 per cent. Glucose and glycogen levels increased progressively. Just before the onset of seizures the levels had increased 95 and 62 per cent, respectively. During the seizures both substances had increased a total of 130 per cent. Comparable changes were found in cerebral cortex, cerebellum and subcortical forebrain. Through the use of quantitative histochemical methods it was found that the greatest increases in glycogen occurred in layers I and III (layers II and IV were not analysed). Progressively smaller changes were found in layers V and VI and no increase at all was found in the subjacent white matter. Glucose, in contrast to glycogen, increased to about the same degree in all cerebral layers and in subjacent white matter. The increase in glycogen after MSO administration may be related to the fact that MSO also causes an increase in the ratio of brain to serum glucose levels. This would indicate that an increase in intracellular glucose had occurred. Ammonia levels were increased 300–400 per cent in both cerebrum and cerebellum. A time study in cerebellum showed that the increase begins early and reaches maximal levels long before the onset of seizures. Glutamate levels were reduced by small but statistically significant amounts in both cerebrum and cerebellum. Administration of methionine sulphoximine completely prevented seizures and the increase in lactate, but did not prevent the increases in glycogen and glucose. The rise in ammonia was reduced but not prevented. During 20 sec of complete ischaemia (decapitation) ATP, P‐creatine and glucose fell somewhat more rapidly than normal in brain of animals undergoing MSO seizures. From the changes it was calculated that the metabolic rate had been increased about 20 per cent by the seizure. A new sensitive and specific enzymic method for determination of tissue ammonia is presented together with evised enzymic procedures for lactate and glutamate.

Cerebral glucose metabolism after portacaval shunting in the rat. Patterns of metabolism and implications for the pathogenesis of hepatic encephalopathy.

“…In half of the animals the electroencephalogram was monitored during the infusions. Arterial blood ammonia levels were measured by the method of Folbergrova et al (13).…”

The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia.

“…Blood samples were immediately deproteinized with 1.2 M perchloric acid. The supernatant solution was neutralized with 2.0 M KHCO3, stored at -80°C, and assayed for the ammonia content using the enzymatic fluorometric method of Folbergrova et al (12). The mean arterial ammonia concentration was used in all calculations for each study.…”

Microdialysate concentration changes do not provide sufficient information to evaluate metabolic effects of lactate supplementation in brain-injured patients

“…29 Glucose levels also differ in gray and white matter in rodents, [29][30][31] with differential gray-white changes during anesthesia, ischemia, and seizures. [32][33][34] Direct measurement of glucose levels in human brain also shows differences in levels and transport parameters in white and gray matter. 35 Thus, white-gray matter differences in metabolite level, blood flow rate, metabolic rate, and responses to injury and anesthesia require a conservative approach to interpret and extrapolate microdialysis results to other brain regions.…”