Contribution of microglia/macrophages to expansion of infarction and response of oligodendrocytes after focal cerebral ischemia in rats.
OBJECTIVE
The purpose of this study was (1) to examine the contribution of microglia and macrophages with their interleukin-1beta production and (2) to assess the vulnerability and response of oligodendrocytes in cerebral infarction.


METHODS
Male Wistar rats were subjected to permanent occlusion of the left middle cerebral artery. Expansion of ischemic infarction and response of oligodendrocytes were investigated together with accumulation of inflammatory cells, production of interleukin-1beta, and disruption of the blood-brain barrier. Apoptotic cell death was inferred from fragmented DNA and the expression of proapoptotic Bax protein.


RESULTS
During expansion of infarction, amoeboid microglia and extravasation of serum albumin were observed not only in the infarcted area but also in the adjacent surviving area, whereas macrophages accumulated along the boundary and granulocytes migrated into the center of the infarction. Both amoeboid microglia and macrophages produced interleukin-1beta, an inflammatory cytokine, during an early ischemic period. Furthermore, macrophages within the infarcted tissue expressed Bax protein and subsequently showed fragmented nuclear DNA. Oligodendrocytes were detected in the infarcted area even after 24 hours following middle cerebral artery occlusion, but they subsequently developed fragmented DNA. A week after onset of ischemia, oligodendrocytes were found to be accumulated in the intact area bordered with the infarct together with reactive astrocytes.


CONCLUSIONS
Our results suggest the importance of amoeboid microglia, macrophages, and their interleukin-1beta production in gradual expansion of cerebral infarction. Resident oligodendrocytes may be resistant to ischemic insults, and oligodendrocytes accumulated at the border of the infarction may participate in tissue repair after cerebral infarction.
Mabuchi
T
T
Department of Internal Medicine and Therapeutics, Division of Strokology, Osaka University Graduate School of Medicine, Osaka, Japan.
Kitagawa
K
K
Ohtsuki
T
T
Kuwabara
K
K
Yagita
Y
Y
Yanagihara
T
T
Hori
M
M
Matsumoto
M
M
D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000276:immunology / Q000473:pathology*; D053938:DNA Fragmentation; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology / Q000473:pathology*; D007375:Interleukin-1 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009836:Oligodendroglia / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D007375:Interleukin-1; D018991:Myelin Proteolipid Protein; D012333:RNA, Messenger