Abstract-The bilateral hemispheric ischemia in rats was induced by the occlusion of bilateral common carotid arteries after permanent electrocauterization of bilateral vertebral arteries at the level of the second cervical vertebra.In ischemic rats, (a) electroencephalograms became flat immediately after occlusion of carotid arteries, and (b) mortalities reached maximum levels at day 3 after recirculation.These results suggested that a constant level of cerebral ischemia was produced in this rat model. Pentobarbital markedly inhibited the mortality in these ischemic rats, whereas cyproheptadine did not.A variety of animal models of cerebral ischemia have been developed in rats (1-4). The development of the 4-vessel occlusion method (1) provided new applications for using rats as a model of bilateral hemispheric ischemia. This model has gained popularity because of the relative ease of preparation and has been used in a variety of experimental studies. However, the level of ischemia ob tained by this method is not constant, because the invisible vertebral arteries of the first cervical vertebra (C1) are electrocauterized, and therefore, it is difficult to confirm the completeness of the electrocauterization (3, 4). The inconsistent results make this model unsuitable for the screening of compounds for therapeutic effects on cerebral infarction. We have found that the vertebral arteries at the level of the second cervical vertebra (C2) are visible in Sprague-Dawley rats and can be completely electrocauterized without fail ure. The vertebral arteries at the level of the second cervical vertebra in rats of the Lewis and F-344 strains were also observed at the same place. This paper reports a method for producing reversible occlusion of the carotid arteries after permanent interruption of the vertebral arteries at the level of C2 in unanes thetized rats and changes in electroence phalograms (EEGs) and mortality in ischemic rats with 4-vessel occlusion. By using this model, we investigated the effects of pen tobarbital and cyproheptadine on the cerebral ischemia in rats.Male rats of the Sprague-Dawley strain, weighing 330-380 g, were used throughout the experiments.The animals were main tained on laboratory food and tap water ad libitum under a well-controlled environment. They were anesthetized with sodium pen tobarbital (50 mg/kg, i.p.) and the vertebral arteries of the second cervical vertebra were exposed carefully after separating the para spiral muscles.The vertebral arteries run through the foramina of C2 and travel beneath the alar foramina of C1. An electro cautery needle was inserted through each foramen of C2 and both vertebral arteries were permanently electrocauterized (Fig. 1 A). Thus, complete occlusion of the vertebral arteries was confirmed by direct observation in all of the operated rats. Immediately after the elec trocauterization, the site of incision was closed carefully. The common carotid arteries were exposed bilaterally through a midline cervical incision and isolated their nerve trunks. The s...