Cerebral metabolic and circulatory changes in the rat during sustained seizures induced by DL-homocysteine

Sustained, generalized seizure activity was induced in anaesthetized (70% N2O), paralyzed and artifically ventilated rats by i.p. DL-homocysteine thiolactone in a dose of 11 mmol/kg. Epileptic discharges in the EEG were accompanied by marked perturbation of tissue metabolites. There was a fall in phosphocreatine concentration to 40% of control but only moderate changes in adenine nucleotides, a marked rise in lactate concentration, and a pronounced increase in the lactate/pyruvate ratio. Excessive amounts of dihydroxyacetone phosphate (and glyceraldehyde phosphate) accumulated, indicating that depletion of NAD+ occurred. There was marked accumulation of ammonia, glutamine and alanine, and reduction in glutamate and aspartate concentrations. Administration of a subconvulsive dose of homocysteine (7.5 mmol/kg) gave rise to changes in ammonia and amino acids, qualitatively similar to those occurring during seizures. It is concluded that although changes in the metabolites of the energy reserve were mainly caused by the induced seizures, those affecting amino acid concentrations were significantly influenced by accumulation of ammonia, secondary to metabolism of injected homocysteine. Cerebral blood flow (CBF) and oxygen utilization (CMRO2) were measured during sustained seizures. CMRO2 rose to 150% of control, with a corresponding increase in CBF.