title: Traumatic brain injury induces prolonged accumulation of cyclooxygenase-1 expressing microglia/brain macrophages in rats.
abstract: Inflammatory cellular responses to brain injury are promoted by proinflammatory messengers. 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 COX-1 expression following brain injury. In control brains, COX-1 expression was localized rarely to brain microglia/macrophages. One to 5 days after injury, we observed a highly significant (p < 0.0001) increase in COX-1+ microglia/macrophages at perilesional areas and in the developing core with a delayed culmination of cell accumulation at day 7, correlating with phagocytic activity. There, cell numbers remained persistently elevated up to 21 days following injury. Further, COX-1+ cells were located in perivascular Virchow-Robin spaces also reaching maximal numbers at day 7. Lesion-confined COX-1+ vessels increased in numbers from day 1, reaching the maximum at days 5-7. Double-labeling experiments confirmed coexpression of COX-1 by ED-1+ and OX-42+ microglia/ macrophages. Transiently after injury, most COX-1+ microglia/macrophages coexpress the activation antigen OX-6 (MHC class II). However, the prolonged accumulation of COX-1+, ED-1+ microglia/macrophages in lesional areas enduring the acute postinjury inflammatory response points to a role of COX-1 in the pathophysiology of secondary injury. We have identified localized, accumulated COX-1 expression as a potential pharmacological target in the treatment of brain injury. Our results suggest that therapeutic approaches based on long-term blocking including COX-1, might be superior to selective COX-2 blocking to suppress the local synthesis of prostanoids.
authors.affiliation: Institute of Brain Research, University of Tuebingen, Medical School, Germany. jmschwab@med.uni-tuebingen.de
authors.forename: J M
authors.initials: JM
authors.lastname: Schwab
authors.forename: K
authors.initials: K
authors.lastname: Seid
authors.forename: H J
authors.initials: HJ
authors.lastname: Schluesener
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D051545:Cyclooxygenase 1; D004660:Encephalitis / Q000378:metabolism / Q000473:pathology; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis*; D008264:Macrophages / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D017628:Microglia / Q000201:enzymology* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000096:biosynthesis*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014951:Wounds, Stab / 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