Antiinflammatory and neuroprotective actions of COX2 inhibitors in the injured brain.
Overexpression of COX2 appears to be both a marker and an effector of neural damage after a variety of acquired brain injuries, and in natural or pathological aging of the brain. COX2 inhibitors may be neuroprotective in the brain by reducing prostanoid and free radical synthesis, or by directing arachidonic acid down alternate metabolic pathways. The arachidonic acid shunting hypothesis proposes that COX2 inhibitors' neuroprotective effects may be mediated by increased formation of potentially beneficial eicosanoids. Under conditions where COX2 activity is inhibited, arachidonic acid accumulates or is converted to eicosanoids via lipoxygenases and cytochrome P450 (CYP) epoxygenases. Several P450 eicosanoids have been demonstrated to have beneficial effects in the brain and/or periphery. We suspect that arachidonic acid shunting may be as important to functional recovery after brain injuries as altered prostanoid formation per se. Thus, COX2 inhibition and arachidonic acid shunting have therapeutic implications beyond the suppression of prostaglandin synthesis and free radical formation.
Strauss
Kenneth I
KI
Mayfield Neurotrauma Research Lab, Department of Neurosurgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML515, Cincinnati, OH 45267, USA. kstrauss@uc.edu
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015777:Eicosanoids / Q000378:metabolism; D005609:Free Radicals / Q000037:antagonists & inhibitors; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D015777:Eicosanoids; D005609:Free Radicals; D018696:Neuroprotective Agents; D011453:Prostaglandins; D016718:Arachidonic Acid