THE TOXICITY TO RAT CEREBRAL CORTEX OF TOPICAL APPLICATIONS OF ACETALDEHYDE, AMMONIA OR BILIRUBIN

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Abstract
The relative toxicity of acetaldehyde, ammonia and bilirubin to cerebral cortex of rats was tested by superfusion of the intact dura for 1 h with each toxin separately. The cortex was examined histologically after 6 days survival using a silver stain which selectively impregnates degenerating axons and their synaptic terminals. A tissue concentration of 30 mM acetaldehyde caused axonal and terminal degeneration, whereas 11 mM acetaldehyde was not toxic, and did not produce any structural changes detectable by EM. In terms of tissue concentrations, acetaldehyde was at least 27 times more toxic than ethanol on a molar basis. The acetaldehyde concentration necessary to produce neuronal degeneration in a 1 h exposure is many times greater than ever reported in CSF in human alcoholism. Both ammonia and bilirubin are capable of causing neuronal degeneration, but the toxic tissue concentrations were not measured. Comparison of molar concentrations in the superfusing fluids showed that ammonia is at least 39 times more toxic than acetaldehyde and at least 1000 times more toxic than ethanol. Superfusion with an ethanolic solution of bilirubin (2.5 mM) was strongly toxic, but this solution diluted to 50% with saline was not toxic. Ammonia or bilirubin may reach concentrations toxic to neurons in alcoholism, especially in the presence of liver damage.