Progressive cortical atrophy after forebrain ischemia in diabetic rats.

The morphological changes in the brain of diabetic rats were examined up to 8 weeks after transient forebrain ischemia produced by transient occlusion of both carotid arteries. Using histochemistry, we also examined the extent and rate of development of atrophic changes in the brain, appearance of astrocytes, activated microglia, and glucose transporter 1 (GLUT1) in streptozotocin-treated rat brains after forebrain ischemia. Atrophic changes appeared in the hippocampus in both non-diabetic-- and diabetic--ischemic groups 4 weeks after ischemia. In diabetic--ischemic rats, the atrophic changes were more severe and progressed more rapidly in the hippocampus, and were also observed in the frontal, temporal and parietal cortices, but not in any cortical areas of the non-diabetic--ischemic rats and non-ischemic--diabetic rats. We observed reduced density of GLUT1 in all cortical regions and hippocampus in ischemic-diabetic rats at 4--8 weeks, when the number of activated microglias and astroglias increased in all cortical regions. Although severe atrophic changes were observed in the gray matter, no serious injury was noted in the white matter in the diabetic-ischemic group. Our results indicate that brain ischemia in the presence of diabetes causes more severe late-onset damage culminating in brain atrophy, compared with non-diabetics.