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. 1967 May;46(5):838–848. doi: 10.1172/JCI105583

Studies on the Intracerebral Toxicity of Ammonia*

Steven Schenker 1,†, David W McCandless 1, Edward Brophy 1, Michael S Lewis 1
PMCID: PMC297085  PMID: 6025485

Abstract

Interference with cerebral energy metabolism due to excess ammonia has been postulated as a cause of hepatic encephalopathy. Furthermore, consideration of the neurologic basis of such features of hepatic encephalopathy as asterixis, decerebrate rigidity, hyperpnea, and coma suggests a malfunction of structures in the base of the brain and their cortical connections.

The three major sources of intracerebral energy, adenosine triphosphate (ATP), phosphocreatine, and glucose, as well as glycogen, were assayed in brain cortex and base of rats given ammonium acetate with resultant drowsiness at 5 minutes and subsequent coma lasting at least 30 minutes.

Cortical ATP and phosphocreatine remained unaltered during induction of coma. By contrast, basilar ATP, initially 1.28 ± 0.15 μmoles per g, was unchanged at 2.5 minutes but fell by 28.1, 27.3, and 26.6% (p < 0.001) at 5, 15, and 30 minutes after NH4Ac. At comparable times, basilar phosphocreatine fell more strikingly by 62.2, 96, 77.1, and 71.6% (p < 0.001) from a control level of 1.02 ± 0.38 μmoles per g. These basilar changes could not be induced by anesthesia, psychomotor stimulation, or moderate hypoxia and were not due to increased accumulation of ammonia in the base. Glucose and glycogen concentrations in both cortex and base fell significantly but comparably during development of stupor, and prevention of the cerebral glucose decline by pretreatment with glucose did not obviate ammonia-induced coma or the basilar ATP fall.

These findings represent the first direct evidence that toxic doses of ammonia in vivo acutely affect cerebral energy metabolism and that this effect is preferentially localized to the base of the brain.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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