Subtle neuronal death in striatum after short forebrain ischemia in rats detected by in situ end-labeling for DNA damage.
OBJECTIVE
Neuronal cell death after global brain ischemia occurs predominantly by necrosis, whereas only a minor fraction of cell death may occur through apoptosis. Brief or moderate insults are thought to facilitate apoptosis, which is associated with DNA fragmentation. After 10 minutes of four-vessel occlusion in rats, conventional neuropathological analysis shows neuronal cell death in hippocampal CA1 but not in the striatum. Thus, we compared hippocampus and striatum for occurrence of cells with DNA fragmentation.


METHODS
A brief insult of 10 minutes of forebrain ischemia was induced in rats using four-vessel occlusion, and groups of brains were studied at 1, 3, 6, and 12 hours and at 1, 3, and 7 days after ischemia. In situ end-labeling (ISEL) was used to detect neurons undergoing DNA fragmentation. The hippocampal CA1 area was compared with the striatum. Conventional staining and immunohistochemical markers served to exclude ischemic neuronal cell death in the striatum.


RESULTS
Hippocampal CA1 neurons were ISEL-positive by 3 days after ischemia. In contrast, positive cells became evident in the striatum between 3 hours to 3 days after ischemia. The ISEL-positive cells were scattered throughout the striatum with a preference for the dorsomedial areas and accounted for about 0.2% of the neurons per striatal area at 1 day. Conventional staining and immunohistochemical markers failed to reveal areas of overt cell damage in the striatum.


CONCLUSIONS
The scattered cell damage in the striatum after brief forebrain ischemia suggests the occurrence of an apoptotic process. The striatum therefore may be prone to subtle cell death due to metabolic insults.
Schmidt-Kastner
R
R
Neuroscience Research Institute, Faculty of Medicine, University of Ottawa, Canada.
Fliss
H
H
Hakim
A M
AM
D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature; D016923:Cell Death; D003342:Corpus Striatum / Q000473:pathology; D004249:DNA Damage; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006624:Hippocampus / Q000473:pathology; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000473:pathology*; D016548:Prosencephalon / Q000098:blood supply / Q000473:pathology*; D017966:Pyramidal Cells / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein