title: Cyclooxygenase-2 does not contribute to postischemic production of reactive oxygen species.
abstract: We sought to determine whether reactive oxygen species (ROS) derived from cyclooxygenase-2 (COX-2) are involved in ischemic brain injury. Focal cerebral ischemia was induced by transient middle cerebral artery occlusion in C57BL/6 mice. The time course of neocortical ROS production was assessed in vivo using hydroethidine as a marker. The same brain sections were used for infarct volume measurements. Transient middle cerebral artery occlusion led to a biphasic increase in ROS production with peaks 2 and 72 h after reperfusion. The COX-2 inhibitor NS398 (10 mg/kg) attenuated the production of COX-2-derived prostaglandin E(2) and reduced brain injury, but did not affect ROS production at 2 and 72 h. Similarly, ROS production was not reduced in COX-2-null mice. In contrast, ROS production and brain injury were reduced in mice lacking the nox2 subunit of the superoxide-producing enzyme nicotinamide adenine dinucleotide phosphate (reduced form) oxidase. The data suggest that COX-2 is not a major source of oxygen radicals after cerebral ischemia and raise the possibility that other COX-2 reaction products, including prostanoids or nonoxygen-based radicals, mediate the COX-2-dependent component of the injury.
authors.affiliation: Division of Neurobiology, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kunz
authors.forename: Josef
authors.initials: J
authors.lastname: Anrather
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Marcello
authors.initials: M
authors.lastname: Orio
authors.forename: Costantino
authors.initials: C
authors.lastname: Iadecola
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors
chemical_list: D017382:Reactive Oxygen Species; D051546:Cyclooxygenase 2