title: The neuroprotective effects of cyclooxygenase-2 inhibition in a mouse model of aneurysmal subarachnoid hemorrhage.
abstract: The CNS inflammatory reaction occurring after aneurysmal subarachnoid hemorrhage (SAH) involves the upregulation of numerous cytokines and prostaglandins. Cyclooxygenase (COX) inhibition is a well-established pharmacological anti-inflammatory agent. Previous studies have shown marked increases in COX-2 expression in neurons, astrocytes, microglia, and endothelial cells following brain injury. COX-2 inhibition has been shown to be beneficial following various types of brain injury. This experiment investigates the role of COX-2 activity in early brain injury following SAH. CD-1 mice were subjected to an endovascular perforation model of SAH or SHAM surgery. Following experimental SAH animals were treated with the specific COX-2 inhibitor, NS398, in dosages of either 10 or 30 mg/kg. Neurological performance and brain edema were evaluated 24 and 72 h after SAH. NS398 at 30 mg/kg significantly reduced SAH-induced neurological deterioration. NS 398 at 30 mg/kg resulted in a trend toward the reduction of SAH-induced cerebral edema. Treatment had no effect on mortality. This experiment provides preliminary evidence that COX-2 inhibition is an effective pharmacological intervention for the prevention of brain edema and the preservation of neurological function following SAH.
authors: Department of Neurosurgery, Loma Linda University Medical Center, Loma Linda, CA, USA.
authors: R
authors: R
authors: Ayer
authors: V
authors: V
authors: Jadhav
authors: T
authors: T
authors: Sugawara
authors: John H
authors: JH
authors: Zhang
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D001930:Brain Injuries / Q000209:etiology / Q000517:prevention & control*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009460:Neurologic Examination; D009578:Nitrobenzenes / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy*; D013449:Sulfonamides / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide