Selective accumulation of cyclooxygenase-1-expressing microglial cells/macrophages in lesions of human focal cerebral ischemia

• Published in: Acta neuropathologica 2000-06, Vol.99 (6), p.609-614
• Main Authors: Schwab, J M, Nguyen, T D, Postler, E, Meyermann, R, Schluesener, H J
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antigens; Apoptosis; Arachidonic acid; Blood flow; Brain - enzymology; Brain - pathology; Brain - physiopathology; Brain Ischemia - enzymology; Brain Ischemia - pathology; Brain Ischemia - physiopathology; Cell activation; Cyclooxygenase 1; Cyclooxygenase-2; Endothelial cells; Female; Histocompatibility antigen HLA; Humans; Immunohistochemistry; Immunomodulation; Inflammation; Ischemia; Isoenzymes - metabolism; Macrophages; Macrophages - enzymology; Macrophages - pathology; Major histocompatibility complex; Male; Membrane Proteins; Microglia; Microglia - enzymology; Microglia - pathology; Microglial cells; Middle Aged; Ovulation; Prostaglandin-Endoperoxide Synthases - metabolism; Prostaglandins
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s004010051170

Cyclooxygenases (COX; prostaglandin endoperoxide H synthases) are key enzymes in the conversion of arachidonic acid into prostanoids which mediate inflammation, immunomodulation, mitogenesis, ovulation, fewer, apoptosis and blood flow. Here, we report COX-1 expression following focal cerebral infarctions (FCI). In healthy control brains, COX-1 was localized by immunohistochemistry to a few endothelial cells, single neurons and rare, evenly distributed brain microglia/macrophages. In infarctioned brains, COX-1+ cells accumulated highly significantly (P < 0.0001) in peri-infarctional areas and in the developing necrotic core early after infarction. Here, cell numbers remained persistently elevated up to several months post infarction. Further, clusters of COX-1+ cells were located in perivascular regions related to the Virchow-Robin space. Double-labeling experiments confirmed co-expression of COX-1 by CD68+ microglia/macrophages. Co-expression of the activation antigens HLA-DR, -DP, -DQ (MHC class II) or the macrophage inhibitor factor-related protein MRP-8 (S100A8) by most COX-1+ microglia/macrophages was only seen early after infarction. Thus, COX-1 appeared to be expressed in microglial cells regardless of their activation state. However, the prolonged accumulation of COX-1+ microglia/macrophages restricted to peri-infarctional areas enduring the acute post-ischemic inflammatory response points to a role of COX-1 in tissue remodeling or in the pathophysiology of secondary injury. We have identified localized, accumulated COX-1 expression as a potential pharmacological target following FCI. Therefore we suggest that therapeutic approaches based on selective COX-2 blocking might not be sufficient for suppressing the local synthesis of prostanoids.