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The four-vessel occlusion (4VO) model of Pulsinelli and Brierley (Stroke 1979; 10:267-272) has been modified for use in halothane-nitrous oxide-anesthetized, physiologically controlled rats that were ventilating spontaneously. Selection criteria for the classification of severity of ischemia were established by correlating changes in the electroencephalogram and the general physiological status with measurements of regional blood flow and regional energy metabolism. In 13% of animals, 4VO did not cause flattening of the electroencephalogram, and such animals were classified as undergoing only "oligemia." In 65% of rats, the electroencephalogram flattened and blood pressure sharply increased with 4VO, whereas spontaneous respiration continued. This group exhibited almost complete ischemia in autoradiographic blood-flow studies, severe acidosis, and depletion of adenosine 5'-triphosphate and glucose in the forebrain and, hence, was classified as the "ischemia" group. The remaining 22% stopped breathing after vascular occlusion and were rejected for further study. Survival experiments of ischemic animals revealed the typical postischemic sequelae, with primary metabolic recovery after 8 hours of recirculation in all brain structures followed after 8-24 hours by severe biochemical deterioration and neuronal death in the striatum and hippocampus. Postischemic seizure activity was rare. The main advantages of the present modification in comparison with the original method are 1) the application of anesthesia without loss of primary selection criteria, 2) the possibility of invasive physiological monitoring, and 3) the absence of postischemic seizures, which eliminates the necessity for secondary selection criteria. (Stroke 1989;20:938-946) I n 1979, Pulsinelli and Brierley 1 described a model of incomplete forebrain ischemia in unanesthetized rats that was produced by occlusion of four major arteries supplying the brain. Four-vessel occlusion (4VO) was performed in two stages: 1) by coagulation of both vertebral arteries through the alar foramen and 2) after a delay of 1 day, by transient occlusion of both common carotid arteries.1 The severity of ischemia is judged by neurological investigation, and animals are then selected for further study on this basis. Received September 19, 1988; accepted February 2, 1989. ischemia by examining neurological signs. For this reason, we have established selection criteria of severe forebrain ischemia that can be applied to anesthetized, spontaneously breathing animals and that are compatible with postischemic survival.Materials and Methods We used 163 adult male Wistar rats of the HanWist strain (Zentralinstitut fur Versuchstiere, Hannover, FRG) (mean body weight, 310 g). On the first day of the experiment, rats were anesthetized in a jar flushed with 4% halothane in 70% nitrous oxide-30% oxygen until unresponsive, placed on a rat operating table (Hugo Sachs, Freiburg, FRG), and maintained under anesthesia with a face mask surrounded by a larger, semiclosed container connec...

Recovery of protein synthesis following 1 h of complete ischemia of the monkey brain was assessed by 3H-labeled amino acid incorporation in vivo at various postischemic periods between 1.5 and 24 h. The regional autoradiographic patterns obtained were compared on the basis of precursor-product relationships determined biochemically at the end of the tracer incorporation studies. Shortly after ischemia, protein synthesis was severely inhibited, but it gradually recovered with increasing recirculation times. In the cerebellum it returned to almost normal levels within 3 h and in the cortex within 24 h. Hippocampal and thalamic regions, however, did not recover control levels of protein synthesis at 24 h. His-toautoradiographic evaluation of amino acid incorporation in individual neurons revealed recovery of pyramidal neurons in the CA1 and CA3 sectors of the hippocampus within 6 h of recirculation, which, however, was followed by secondary inhibition after longer recirculation. Neurons in cortical layer 5 steadily recovered to near control within 24 h, with the exception of those located in arterial border zones, which returned to only 50% of control at 24 h. Incomplete recovery was also observed in thalamic neurons and Purkinje cells. The regional and histoauto-radiographic pattern of protein synthesis correlated with the morphological appearance of cells. Ischemic cell changes (mainly of the dark type with microvacuolization and perineuronal glial swelling) were marked after short recirculation times but gradually disappeared in parallel with the return of protein synthesis in most regions of the brain. Only in pyramidal cells of the hippocampus, thalamic neurons, and Purkinje cells were changes not reversed during the observation period. The results obtained corroborate the electrophysiological observations reported in the first part of this investigation and support the notion that the majority of the neurons of monkey brain survive complete cerebrocirculatory arrest of 1 h for at least 1 day.

Summary: Adult normothermic monkeys were sub mitted to 1 h of total cerebral ischemia. followed by blood recirculation for 1.5-24 h. During ischemia EEG and evoked potentials were suppressed within 12 sand 3 min. respectively. Upon recirculation. high-voltage EEG bursts began to reappear after 82-125 min. followed by gradual return of continuous background activity and near normalization of EEG frequency pattern within 24 h. Somatically evoked potentials. in contrast, exhibited only partial recovery. and consciousness did not return during the observation period. At the end of the experi ments. tissue contents of sodium. potassium. calcium. and magnesium were measured in the gray and white matter of parietal lobe by atomic absorption spectros-