Characterization of a recovery global cerebral ischemia model in the mouse

Transgenic/knockout murine variants allow roles of specific proteins to be studied in cerebral ischemia. Because of the size of mice, however, study o f prolonged recovery from global ischemia has been limited. This project ch aracterized an adaptation of the rat two-vessel occlusion model of global i schemia for use in the mouse. C57B1/6J mice (8 weeks old; 21 +/- 1 g) were overnight fasted, anesthetized with halothane, intubated and mechanically v entilated. The right internal jugular vein and femoral artery were cannulat ed. Pericranial temperature was held at 37.0 degrees C, The carotid arterie s were occluded and mean arterial pressure was reduced to 35 mmHg with 0.3 mg intra-arterial trimethaphan and venous exsanguination. Electroencephalog raphic isoelectricity was confirmed in cohort mice. Ten minutes later ische mia was reversed. Mice were allowed 1, 3 or 5 days survival followed by his tologic analysis. Regional cerebral blood flow (CBF) was determined autorad iographically. Outcome effects of intra-ischemic hyperglycemia (approximate to 350 mg/dl) or hypothermia (34 degrees C) were also examined. The mortal ity rate was less than 10% in all recovery groups. Ischemia caused reductio n of CBF to < 2% of sham values in cortex, hippocampus, and caudoputamen. C BF was unchanged in thalamus, brainstem and cerebellum. CAl damage, greater after 3 days vs. 1 day reperfusion, was not further increased at 5 days. H istologic injury was increased by hyperglycemia although seizures did not o ccur. Hypothermia reduced CAI damage. This study demonstrates feasibility o f using the two-vessel occlusion + hypotension recovery model in the mouse. Recovery intervals of greater than or equal to 3 days are required to acco unt for delayed CAl neuronal necrosis. Histologic outcome can be modulated by known physiologic determinants of ischemic brain damage. (C) 1999 Elsevi er Science B.V. All rights reserved.