Glial damage after transient focal cerebral ischemia in rats.
We investigated the immunohistochemical changes of 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunoreactivity as a marker of DNA damage and single-strand DNA (ssDNA) immunoreactivity as a marker of apoptosis in the striatum from 1 up to 15 days after 90 min of focal cerebral ischemia caused by middle cerebral artery occlusion in rats. In the present study, marked loss of MAP2 immunostaining was observed in the ipsilateral striatum 3 days after focal cerebral ischemia. A significant increase in the number of ssDNA-immunoreactive apoptotic neurons was observed in the ipsilateral striatum 1 and 3 days after focal cerebral ischemia. In contrast, a significant increase in densities of 8-OHdG-immunopositive cells was observed in the ipsilateral striatum from 3 up to 15 days after focal cerebral ischemia. Our double-labeled immunochemical study showed that 8-OHdG immunoreactivity was observed in both isolectin B(4)-positive microglia and glial fibrillary acidic protein-immunopositive astrocytes in the ipsilateral striatum 7 days after focal cerebral ischemia. These results suggest that focal cerebral ischemia can cause a marked increase in the number of microglia and astrocytes with oxidative DNA damage in the ipsilateral striatum. Furthermore, our results show that most microglia and astrocytes in the ipsilateral striatum after focal cerebral ischemia may not die by apoptosis. Thus, our findings provide novel evidence that focal cerebral ischemia can cause oxidative DNA damage in most microglia and astrocytes.
Matsuda
Shunsuke
S
Department of Neurobiology and Therapeutics, Graduate School and Faculty of Pharmaceutical Sciences, The University of Tokushima, 1-78, Sho-machi, Tokushima, 770-8505, Japan.
Umeda
Masahiro
M
Kato
Hiroyuki
H
Araki
Tsutomu
T
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D004277:DNA, Single-Stranded / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D009457:Neuroglia / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004277:DNA, Single-Stranded; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine