EFFECT OF GLOBAL-ISCHEMIA, UNDER SIMULATED PENUMBRAL CONDITIONS, ON BRAIN MONOAMINE NEUROCHEMISTRY AND SUBSEQUENT NEUROLOGICAL AND HISTOLOGICAL DEFICITS

We have measured changes in the levels of dopamine (DA), 5-hydroxytryp tamine (5-HT), and their metabolites in striatal dialysates during 30 min of global ischaemia under simulated penumbral conditions, and comp ared these with neurological assessments over the following 7 days and histological damage at the end of this period. On the basis of dialys ate DA levels during ischaemia, the animals fell into two subgroups; g roup I with little or no DA increase (less than three times basal); an d group II, with a much larger increase (greater than 30 times basal). Changes in 5-HT, though of lesser magnitude, showed a similar pattern . These findings may indicate that the amine changes depend on a criti cal reduction of blood flow within the range obtained by our experimen tal procedure. Levels of deaminated metabolites fell in all ischaemic animals, with comparable decreases of 3,4-dihydroxyphenylacetic acid p lus homovanillic acid in both groups. Decreases of 5-hydroxyindoleacet ic acid were greater in group II than in group I, but the relative dif ferences between the groups were much less marked than those of 5-HT. These neurochemical findings suggest that moderate ischaemia affects e xtracellular amine and deaminated metabolite levels by different mecha nisms. Only one of the ischaemic rats (a member of group II) showed a marked neurological deficit, but histological damage, as indicated by neuronal loss and gliosis in vulnerable structures, was apparent in al l ischaemic animals. Although damage tended to be greater in animals w ith marked increases in extracellular monoamines, differences were not significant. These findings suggest that the large increases of extra cellular DA and 5-HT that sometimes occur in ischaemia may play a rela tively small part in the genesis of neuronal damage, though these tran smitters may well have a permissive role.