Ischemia is a major cause of damage to the central nervous system as a consequence of stroke or trauma. Here, we analyzed with high temporal resolution the time course of pathological changes in the neurons (granule and Purkinje cells) and glia (Bergmann and astroglia cells) in the cerebellar cortex and white matter. The period studied ranged from 30 min to 7 days after a microsphere-induced embolism used as a model of stroke and multi-infarct dementia. Some pathological changes in the neurons in the cerebellar cortex were identified early, that is, beginning at 3 h after the microsphere-induced embolism, and glial pathology appeared only later. The pathological changes in the white matter also appeared slightly later, that is, 6 It after embolism and were less pronounced than those in the cerebellar cortex. This suggests that neuronal pathology is induced more rapidly and/or more easily than the glial pathology. In addition, BrdU staining shows that cell proliferation is limited to a 1-day period beginning about 1 day after the embolism. These data demonstrate that changes after an ischemic lesion of the cerebellum proceeds from upper cerebellar cortex to deeper cerebellar cortex or white matter and also that microsphere-induced changes proceed from neuronal to glial pathology. (C) 2004 Elsevier Inc. All rights reserved.