Diabetic Chronic Hyperglycemia and Neurologic Outcome following Global Ischemia in Dogs

We tested the hypothesis that the neuropathologic outcome following recovery from incomplete ischemia is similar in normoglycemia and diabetes. Incomplete global ischemia was induced for 20 min in two groups of dogs: (a) normoglycemic, nondiabetic controls (n = 11) and (b) chronic (3 months), diabetic hyperglycemic subjects (n = 12). Animals were allowed to recover from surgery for 7 days after which they were perfusion-fixed for neuropathology. On paraffin processed tissue stained with hematoxylin and eosin (H&E), ischemic neurons were counted and the per cent of cell damage determined. All control animals survived for 7 days postischemia. Four of 12 diabetic animals survived for 7 days, with the remaining eight diabetic dogs dying within the first 3 days. On day 7, the percentage of neurons showing ischemic cell change in the four diabetic survivors and the 11 nondiabetic controls was similar in the cerebellum, CA1, superior temporal gyrus, and caudate. However, diabetic dogs that did not survive the 7-day recovery period showed cerebellar swelling, reduced Purkinje cell densities, and herniation. During the 3 months prior to ischemia, morning (10.7 ± 4.4 versus 11.2 ± 5.2 m M) and afternoon (8.8 ± 5.0 versus 9.4 ± 5.3 m M) blood glucose levels in the four surviving and eight nonsurviving diabetic animals, respectively, were similar. However, preischemic blood glucose was significantly elevated in animals that did not survive (7.8 ± 2.8 versus 15.8 ± 7.3 m M in survivors and nonsurvivors, respectively). This study shows that diabetic animals surviving 7 days postischemia and nondiabetic controls have similar neuropathology. However, diabetic animals in which glucose control deteriorated during the 24-h prior to ischemia did not survive, possibly due to severe hindbrain edema. These results show that in diabetes, blood glucose control immediately prior to incomplete global brain ischemia is an important determinant of morbidity and neuropathology.