Abstract
Reversible cerebral ischemia was produced in anesthetized Mongolian gerbils by occluding both common carotid arteries. After 5 min of ischemia, brains were recirculated for 8 or 24 h. Treated animals received a single intraperitoneal injection of pentobarbitol (50 mg/kg) immediately after the anuerysm clips were removed. At the end of the experiments, animals were reanesthetized and their brains frozen in situ. Tissue samples were taken from the cerebral cortex, lateral striatum, CA1 subfield of the hippocampus, thalamus, and cerebellum for measuring ornithine decarboxylase (ODC) activity and putrescine levels. In addition, 20-μm-thick coronal tissue sections were taken from the level of the striatum and stained with hematoxylin/eosin for evaluating the extent of ischemic neuronal necrosis in the lateral striatum. In control animals ODC activity and putrescine levels amounted, respectively, to 0.32 ± 0.03 nmol/g/h and 10.2 ±0.5 nmol/g in the cerebral cortex; 0.34 ± 0.02 nmol/g/h and 12.8 ± 0.5 nmol/g in the lateral striatum; 0.58 ± 0.05 nmol/g/h and 10.5 ± 0.7 nmol/g in the hippocampal CA1 subfield; 0.35 ± 0.01 nmol/g/h and 9.8 ± 0.4 nmol/g in the thalamus; and 0.25 ± 0.01 nmol/g/h and 8.3 ± 0.6 nmol/g in the cerebellum. After 5 min cerebral ischemia and 8 h recirculation, a significant 7- to 16-fold increase in ODC activity was observed in all forebrain structures studied. Following 24 h recirculation, ODC activity normalized in the cortex, striatum, and thalamus but was still significantly above control values in the hippocampal CA1 subfield. In the cerebellum ODC activity did not change significantly. Putrescine levels were significantly increased in all forebrain structures after 8 h (two- to threefold) and even more after 24 h recirculation (up to fivefold). In barbiturate-treated animals, ODC activity was not significantly changed in relation to untreated ones. There was, however, a trend to higher activity in the cerebral cortex, lateral striatum, and hippocampal CA1 subfield. Barbiturate did not produce a significant effect on postischemic putrescine levels except in the CA1 subfield. Here the putrescine content of treated animals was significantly below that found in untreated ones. In the lateral striatum, severe cell damage (>90% of neurons were necrotic) was observed in 5 of 12 untreated animals but in none of the barbiturate-treated ones (<10% of neurons necrotic). In animals with severe cell necrosis in the lateral striatum, putrescine levels amounted to 70.9 ± 3.4 nmol/g but to only 32.0 ± 2.9 nmol/g in animals in which <10% of neurons were affected (p ⩽ 0.001).