Contribution of microglia/macrophages to expansion of infarction and response of oligodendrocytes after focal cerebral ischemia in rats

Background and Purpose-The purpose of this study was (1) to examine the con tribution of microglia and macrophages with their interleukin-lp production and (2) to assess the vulnerability and response of oligodendrocytes in ce rebral infarction. Methods-Male Wistar rats were subjected to permanent occlusion of the left middle cerebral artery. Expansion of ischemic infarction and response of ol igodendrocytes were investigated together with accumulation of inflammatory cells, production of interleukin-1 beta, and disruption of the blood-brain barrier. Apoptotic cell death was inferred from fragmented DNA and the exp ression of proapoptotic Bar protein. Results-During expansion of infarction, amoeboid microglia and extravasatio n of serum albumin were observed not only in the infarcted area but also in the adjacent surviving area, whereas macrophages accumulated along the bou ndary and granulocytes migrated into the center of the infarction. Both amo eboid microglia and macrophages produced interleukin-1 beta, an inflammator y cytokine, during an early ischemic period. Furthermore, macrophages withi n the infarcted tissue expressed Bar protein and subsequently showed fragme nted nuclear DNA. Oligodendrocytes were detected in the infarcted area even after 24 hours following middle cerebral artery occlusion, but they subseq uently developed fragmented DNA. A week after onset of ischemia, oligodendr ocytes were found to be accumulated in the intact area bordered with the in farct together with reactive astrocytes. Conclusions-Our results suggest the importance of amoeboid microglia, macro phages, and their interleukin-1 beta production in gradual expansion of cer ebral infarction. Resident oligodendrocytes may be resistant to ischemic in sults, and oligodendrocytes accumulated at the border of the infarction may participate in tissue repair after cerebral infarction.