Brain ornithine decarboxylase activity following transient cerebral ischaemia: relationship to cerebral oedema development

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Abstract
Ornithine decarboxylase (ODC) activity, the first and generally rate-limiting enzyme for polyamine synthesis, is stimulated in permanent focal cerebral ischaemia in areas of incomplete ischaemia which are developing ischaemic brain oedema. As polyamines are ubiquitous ornithine-derived molecules which are obligatory in cold-induced vasogenic oedema, we studied the effect of transient dense cerebral ischaemia with reperfusion on ischaemic oedema development and ODC activity. Fifty-nine Mongolian gerbils were anaesthetized with ketamine hydrochloride (160 mg/kg i.p. plus supplementation as needed). Both common carotid arteries were isolated and a tracheotomy placed in position. EEG was monitored with needle electrodes and temperature maintained at 37-38°C. Twenty-nine gerbils underwent 40 min of bilateral carotid artery occlusion followed by reperfusion times of 10 min, 1, 2, 4, 6 or 8 h. Non-ischaemic control groups were monitored for equal intervals. At sacrifice, the brain was rapidly removed and forebrain samples analysed for ODC activity (enzymatic assay) and cerebral oedema (gravimetric determination). Marked loss of EEG amplitude was noted in all gerbils subjected to bilateral carotid artery occlusion. Ischaemia produced significant levels of cortical oedema throughout the reperfusion period (maximal decrease in specific gravity at 4 h postischaemia; control: 1.0456 ± 0.0013; ischaemia: 1.0355 ± 0.0021, mean ± SD; p > 0.0001). Significant subcortical oedema was produced at 10 min, 2 and 4 h postischaemia. A biphasic response was observed in brain ODC activity. Throughout the first 2 h of reperfusion, ODC activity was significantly depressed in ischaemic versus control animals (10 min: 1423 ± 824 versus 3049 ± 1019; 1 h: 704 ± 635 versus 2621 ± 902; 2 h: 348 ± 184 versus 3654 ± 2072 pmoles/g tissue/60 min; p > 0.05). This difference was no longer detectable by 4 h postischaemia and by 6 h, ODC levels were significantly higher in ischaemic animals (ischaemia: 9314 ± 2652; control: 3065 ± 2000 pmoles/g tissue/60 min; p > 0.01). Although not significant, ODC was also greater in ischaemic animals at 8 h postischaemia. ODC levels at 6 and 8 h postischaemia were significantly higher (p > 0.05) than ODC levels at 10 min, 1 and 2 h postischaemia among ischaemic animals. These data indicate that transient ischaemia initially suppresses then stimulates ODC activity over the initial 8 h following transient global ischaemia in the gerbil. Since stimulation of ODC activity does not occur until early cerebral oedema is established, it is unlikely that polyamines are involved in the early cytotoxic oedema. Later stages of ischaemic oedema, however, with mixed cytotoxic and vasogenic components may be affected by the delayed rise in ODC activity after transient ischaemia.

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