Sustained
hyperammonemia resulting from portocaval anastomosis (PCA) in the rat, is accompanied by neurological symptoms and reversible morphological changes in brain, the nature and distribution of which suggest selective vulnerability of certain brain structures. The present study was initiated to investigate the effects of increasing CNS
ammonia on the distribution of
amino acids in regions of the rat brain in relation to the degree of neurological impairment in PCA rats. Four weeks following PCA, rats were administered
ammonium acetate (5.2 mmol/kg, i.p.) to precipitate neurological symptoms of
encephalopathy which included diminished locomotor activity, loss of hindlimb extension and righting reflexes and ultimately
coma. At various stages during the development of
encephalopathy, rats were sacrificed and the
amino acids glutamine,
glutamate and
aspartate measured simultaneously, using a sensitive double-
isotope dansyl microassay. Homogenates of the following regions of the CNS were assayed: cerebral cortex, hippocampus, striatum, midbrain, hypothalamus, cerebellum, medulla-pons, spinal cord (gray matter) and spinal cord (white matter). Sustained
hyperammonemia associated with PCA alone resulted in a non-uniform 2-4 fold increase of
glutamine in all regions of the CNS.
Glutamate, on the other hand, was selectively increased in striatum and cerebellum, two regions of brain shown to exhibit early morphologically-characterised astrocytic abnormalities in rats with PCA. Onset of severe neurological dysfunction was accompanied by significantly decreased
glutamine and
glutamate in striatum and cerebellum. Thus, sustained
hyperammonemia in association with portocaval shunting results in region-selective effects with respect to
glutamine-
glutamate metabolism in the CNS.