In spontaneously hypertensive rats, we studied the participation of xanthine oxidase-linked free radical in ischemia and reperfusion-induced cerebral injury, using allopurinol, a xanthine oxidase inhibitor. The loss of righting reflex was noted in some animals after a 4 hour occlusion of bilateral common carotid arteries and 19 of 25 animals died within 72 hours after reperfusion. One hour after reperfusion, the cerebral water content increased significantly, with an increase in sodium content and a decrease in potassium content. In 7 animals treated with oral administrations of allopurinol (200 mg/kg) 24 hours and 1 hour before occlusion, no death was found either during occlusion or after reperfusion, and the loss of righting reflex was noted in only one animal 24-72 hours following reperfusion. The increase in cerebral water content and accompanied changes in electrolyte contents were clearly prevented by allopurinol. These results suggest the possibility that the production of xanthine oxidase-linked free radical participates in cerebral injury due to ischemia and reperfusion in spontaneously hypertensive rats.

We examined the brain damage following repeated hypotensive episodes in the rat. Severe hypotension was induced by withdrawal of arterial blood. The MABP was maintained at about 25 mm Hg with isoelectric EEG and the shed blood was retransfused. After 1 week of recovery, histopathological changes were examined. No brain damage was observed after 1 min of isoelectric EEG. Mild neuronal damage to the hippocampal CA1 subfield was seen in some animals after two episodes of 1-min isoelectric EEG at a 1-h interval. Significant and consistent neuronal loss in the hippocampal CA1 subfield was observed after three episodes of 1-min isoelectric EEG. Scattered neuronal damage in the thalamus was additionally seen in some animals. The present study indicates that repeated brief hypotensive episodes produce brain damage depending on the number of episodes, even though no brain damage results when induced as a single insult. This animal model may reproduce hemodynamic transient ischemic attacks in humans.

A new shock model in the rat using hemorrhagic hypotension for production of brain damage is described. Hemorrhagic shock was induced by lowering arterial blood pressure with bleeding. The MABP was maintained at approximately 25 mm Hg, accompanied by isoelectric EEG, and then shed blood was retransfused. At 1 week of recovery, morphological and 45Ca autoradiographic changes were examined. No brain damage was observed in rats after 1 min of isoelectric EEG. Mild neuronal damage in the hippocampal CA1 subfield was seen in some animals after 2 min of isoelectric EEG. Severe and consistent neuronal loss in the hippocampal CA1 subfield was recognized after 3 min of isoelectric EEG. Additional damage was also seen in the dentate hilus and the thalamus in some animals. This model can be used to study the pathophysiology of postshock brain damage and to assess new therapies following shock.

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