Noradrenaline Metabolism in Neocortex and Hippocampus Following Transient Forebrain Ischemia in Rats: Relation to Development of Selective Neuronal Necrosis

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Abstract
Noradrenaline (NA) metabolism in the neocortex and hippocampus was examined in rats 1, 24, and 48 h following 15 min of reversible forebrain ischemia. As assessed by the ratio of accumulated 3, 4-dihydroxyphenylalanine (DOPA) to the tissue NA level after inhibition of DOPA decarboxylase, the NA turnover rates were markedly increased (120-148% above the control) at 1 h postischemia in both the neocortex and hippocampal formation (CA1 and CA3 plus dentate gyrus). The DOPA:NA ratio went back to control levels after longer postischemic survival times. The ratio between levels of the deaminated NA metabolite, 3,4-dihydroxyphenylethyleneglycol (DOPEG), and NA, which gives another measure of NA turnover rate, showed similar changes. In the neocortex and the Ca3 plus dentate gyrus, the DOPEG:NA ratio was markedly increased (89-118%) 1 h after the ischemia, but this change had disappeared at 24 and 48 h. Thus, both the DOPA accumulation experiments and the NA and DOPEG measurements indicate that following transient forebrain ishcemia, there is an increased NA turnover in the hippocampus and cortex only in the early recirculation period and not after longer postischemic survival times. The degree of neuronal necrosis in the Ca1 region was examined light microscopically on celestine blue-acid fuchsin-stained sections at 24, 48, adn 96 h following the ischemic insult. The neuronal damage in CA1 was sparse after 24 h of recovery, had increased markedly after 48 h and was very pronounced at 96 h. Our data show that the changes in NA turnover in the neocortex and hippocampus follow a different time course than the development of neuronal damage in the hippocampal Ca1 region. The activation of the Na system occurs during and immediately after the period of high extracellular levels of glutamate. Excitatory amino acids have been proposed to be of major importance for the development of ischemic brain damage, whereas the NA afferents to the hippocampus and cortex (originating in the locus coeruleus) seem to have a protective role. We hypothesize that the increased activity of the locus coeruleus system, observed early postischemically in the present study, mitigates the detrimental effects evoked by excessive glutamate receptor stimulation, thereby reducing the degree of neuronal necrosis.