Celecoxib induces functional recovery after intracerebral hemorrhage with reduction of brain edema and perihematomal cell death

J Cereb Blood Flow Metab. 2004 Aug;24(8):926-33. doi: 10.1097/01.WCB.0000130866.25040.7D.


The selective cyclooxygenase-2 (COX-2) inhibitor has been reported to have antiinflammatory, neuroprotective, and antioxidant effects in ischemia models. In this study, the authors examined whether a selective COX-2 inhibitor (celecoxib) reduces cerebral inflammation and edema after intracerebral hemorrhage (ICH), and whether functional recovery is sustained with longer treatment. ICH was induced using collagenase in adult rats. Celecoxib (10 or 20 mg/kg) was administered intraperitoneally 20 minutes, 6 hours, and 24 hours after ICH and then daily thereafter. Seventy-two hours after ICH induction, the rats were killed for histologic assessment and measurement of brain edema and prostaglandin E2. Behavioral tests were performed before and 1, 7, 14, 21, and 28 days after ICH. The brain water content of celecoxib-treated rats decreased both in lesioned and nonlesioned hemispheres in a dose-dependent manner. Compared with the ICH-only group, the number of TUNEL-positive, myeloperoxidase-positive, or OX42-positive cells was decreased in the periphery of hematoma and brain prostaglandin E2 level was reduced in the celecoxib-treated group. Celecoxib-treated rats recovered better by the behavioral tests at 7 days after ICH throughout the 28-day period, and the earlier the drug was administered, the better the functional recovery. Evidence of similar effects in an autologous blood-injected model showed that direct collagenase toxicity was not the major cause of inflammation or cell death. These data suggest that celecoxib treatment after ICH reduces prostaglandin E2 production, brain edema, inflammation, and perihematomal cell death in the perihematomal zone and induces better functional recovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Edema / drug therapy*
  • Brain Edema / pathology
  • Celecoxib
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / pathology
  • Cerebral Hemorrhage / physiopathology
  • Collagenases / toxicity
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Dinoprostone / analysis
  • Dose-Response Relationship, Drug
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Male
  • Neuroprotective Agents / therapeutic use*
  • Pyrazoles
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Sulfonamides / therapeutic use*
  • Time Factors


  • Cyclooxygenase Inhibitors
  • Neuroprotective Agents
  • Pyrazoles
  • Sulfonamides
  • Collagenases
  • Celecoxib
  • Dinoprostone