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Activation Of Cyclo‐Oxygenase‐2 Contributes To Motor And Cognitive Dysfunction Following Diffuse Traumatic Brain Injury In Rats
Author(s) -
Cernak I,
O'Connor C,
Vink R
Publication year - 2001
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2001.03549.x
Subject(s) - traumatic brain injury , hippocampus , nimesulide , medicine , endocrinology , anesthesia , pharmacology , psychiatry
SUMMARY 1. Post‐traumatic inflammation may play a significant role in the development of delayed secondary brain damage following traumatic brain injury. 2. During post‐traumatic inflammation, metabolic products of arachidonic acid, known as prostanoids (prostaglandins and thromboxanes) are released and aggravate the injury process. Prostanoid synthesis is regulated by the enzyme cyclo‐oxygenase (COX), which is present in at least two isoforms, COX‐1 (the constitutive form) and COX‐2 (the inducible form). 3. In the present study, we examine the temporal and spatial profiles of COX‐2 expression and the effects of the COX‐2 inhibitor nimesulide on motor and cognitive outcome following diffuse traumatic brain injury in rats. 4. Adult male Sprague‐Dawley rats were injured using the 2 m impact acceleration model of diffuse traumatic brain injury. At preselected time points after injury, animals were killed and the expression of COX‐2 was measured in the cortex and hippocampus by western blotting techniques. 5. Increased expression of COX‐2 was found in the cortex at 3 days and in the hippocampus as early as 3 h postinjury and this persisted for at least 12 days. 6. Administration of nimesulide (6 mg/kg, i.p.) at 30 min after injury and daily over a 10 day post‐traumatic neurological assessment period resulted in a significant improvement compared with vehicle (2% dimethylsulphoxide diluted in isotonic saline)‐treated controls in cognitive deficits, as assessed by the Barnes circular maze. There was also a significant improvement in motor dysfunction as assessed by the rotarod test on days 1 and 2 post‐trauma compared with vehicle‐treated controls. 7. These results implicate the involvement of COX‐2 in cognitive and motor dysfunction following diffuse traumatic brain injury.