creators_name: Candelario-Jalil, Eduardo creators_name: Fiebich, Bernd L. creators_id: ecandelario-jalil@salud.unm.edu type: journalp datestamp: 2008-07-13 11:04:04 lastmod: 2011-03-11 08:57:09 metadata_visibility: show title: Cyclooxygenase inhibition in ischemic brain injury. ispublished: pub subjects: neuro-chem full_text_status: public keywords: cyclooxygenase-2, ischemia, stroke, cerebral ischemia, neuroinflammation, excitotoxicity abstract: Neuroinflammation is one of the key pathological events involved in the progression of brain damage caused by cerebral ischemia. Metabolism of arachidonic acid through cyclooxygenase (COX) enzymes is known to be actively involved in the neuroinflammatory events leading to neuronal death after ischemia. Two isoforms of COX, termed COX-1 and COX-2, have been identified. Unlike COX-1, COX-2 expression is dramatically induced by ischemia and appears to be an effector of tissue damage. This review article will focus specifically on the involvement of COX isozymes in brain ischemia. We will discuss issues related to the biochemistry and selective pharmacological inhibition of COX enzymes, and further refer to their expression in the brain under normal conditions and following excitotoxicity and ischemic cerebral injury. We will review present knowledge of the relative contribution of each COX isoform to the brain ischemic pathology, based on data from investigations utilizing selective COX-1/COX-2 inhibitors and genetic knockout mouse models. The mechanisms of neurotoxicity associated with increased COX activity after ischemia will also be examined. Finally, we will provide a critical evaluation of the therapeutic potential of COX inhibitors in cerebral ischemia and discuss new targets downstream of COX with potential neuroprotective ability. date: 2008 date_type: published publication: Current Pharmaceutical Design volume: 14 number: 14 publisher: Bentham Science Publishers pagerange: 1401-1418 refereed: TRUE referencetext: References 1. Feigin VL, Lawes CM, Bennett DA, Anderson CS. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol 2003; 2(1):43-53. 2. Truelsen T, Piechowski-Jozwiak B, Bonita R, Mathers C, Bogousslavsky J, Boysen G. Stroke incidence and prevalence in Europe: a review of available data. Eur J Neurol 2006; 13(6):581-598. 3. The Atlas of Heart Disease and Stroke. http://www.who.int/cardiovascular_diseases/resources/atlas/en/index.html. 2004. Ref Type: Internet Communication 4. Paul SL, Srikanth VK, Thrift AG. 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