title: Persistent accumulation of cyclooxygenase-1 (COX-1) expressing microglia/macrophages and upregulation by endothelium following spinal cord injury.
abstract: Acute inflammation following spinal cord injury results in secondary injury and pathological reorganisation of the central nervous system (CNS) architecture. Cyclooxygenases (Prostaglandin Endoperoxide H Synthases, PGH) are key enzymes in the conversion of arachidonic acid into prostanoids which mediate immunomodulation, mitogenesis, apoptosis, blood flow, secondary injury (lipid peroxygenation) and inflammation. Here, we report cyclooxygenase-1 (COX-1) expression following spinal cord injury. In control spinal cords, COX-1 expression was localized by immunohistochemistry to ependymal cells, some neurons, inclusive dorsal and ventral root ganglion cells, few endothelial cells but rarely to brain microglia/macrophages. In injured spinal cords, COX-1(+) microglia/macrophages accumulated highly significantly (P<0.0001) at peri-lesional areas and in the developing necrotic core early after injury. Here numbers of COX-1(+) cells remained persistently elevated up to 4 weeks following injury. Further, COX-1(+) cells were located in perivascular Virchow-Robin spaces, between spared axons and in areas of Wallerian degeneration. Double labeling experiments confirmed co-expression of COX-1 by ED-1(+) and OX-42(+) microglia/macrophages. Transiently after infarction most COX-1(+) microglia/macrophages coexpress the activation antigen OX-6 (MHC class II). However, the prolonged accumulation of COX-1(+) microglia/macrophages at the lesion site enduring the acute post injury inflammatory response points to a role of COX-1 in tissue remodeling or secondary injury. We have identified and localized persistent accumulation of COX-1 expressing cells which might be a potential pharmacological target following spinal cord injury. Therefore, we suggest that approaches based on: (i) short-term; and (ii) selective COX-2 blocking alone might not be a sufficient tool to suppress the local synthesis of prostanoids.
authors.affiliation: Institute of Brain Research, University of Tuebingen, Medical School, Calwer Strasse 3, D-72076, Tuebingen, Germany. jmschwab@med.uni-tuebingen.de
authors.forename: J M
authors.initials: JM
authors.lastname: Schwab
authors.forename: K
authors.initials: K
authors.lastname: Brechtel
authors.forename: T D
authors.initials: TD
authors.lastname: Nguyen
authors.forename: H J
authors.initials: HJ
authors.lastname: Schluesener
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins; D017628:Microglia / Q000201:enzymology*; D009187:Myelitis / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D013119:Spinal Cord Injuries / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat