The effect of hypoxia on the pentose phosphate pathway in brain.

Abstract

Abstract—Tyrosine hydroxylase (TH), dopa decarboxylase (DDC), glutamic acid decarboxylase (GAD), choline acetyltransferase (CAT), and acetylcholinesterase (AChE) were measured in 18–55 areas of brain from humans post mortem. Individuals meeting sudden and unexpected death (22), patients dying in hospital with non–neurological illness (6), Parkinson's disease (12), Huntington's chorea (8), terminal coma (6) or head injury (2) were included in the series. The absolute values obtained compared favourably with some previous human studies where high values for these enzymes were obtained, as well as with monkey and baboon data. The regional distributions of the enzymes were also comparable to those previously reported in human and animal studies. A number of important points with regard to human tissue seemed to emerge from the study. The mode of death was not a factor in enzyme levels in non–neurological and non‐coma cases. Post mortem delay did not seem to be a major factor either even though a substantial decline in GAD, TH and DDC could be demonstrated in rats left several hours between sacrifice and removal of the brain for assay. Age had a highly significant effect in certain areas of brain. The decline typically followed a curvilinear pattern (activity = A/age + B with the sharpest drops being in the younger age groups). DDC seemed to be the enzyme most severely affected by age but all the enzymes showed declines in certain brain areas, while in other areas there was no significant decline. All the enzymes were very depressed by coma from illness except AChE. TH and DDC in the brain stem were, however, not affected in the head injury cases. The Parkinsonian cases showed a sharply decreased TH activity in the substantia nigra, caudate and putamen. There were decreases in GAD in the globus pallidus (GP) and substantia nigra with marginal decreases in the neostriatum. CAT levels in the extrapyramidal nuclei were normal. In Huntington's chorea there was a substantial decrease in GAD in all the extrapyramidal structures. There was a patchy loss of CAT in the neostriatum and locus coeruleus.