The neuroprotective effects of cyclooxygenase-2 inhibition in a mouse model of aneurysmal subarachnoid hemorrhage

Acta Neurochir Suppl. 2011:111:145-9. doi: 10.1007/978-3-7091-0693-8_24.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain Edema / etiology
  • Brain Edema / prevention & control
  • Brain Injuries / etiology
  • Brain Injuries / prevention & control*
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Neurologic Examination
  • Nitrobenzenes / therapeutic use*
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / drug therapy*
  • Sulfonamides / therapeutic use*
  • Time Factors

Substances

  • Cyclooxygenase 2 Inhibitors
  • Nitrobenzenes
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide