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Type: Journal article
Title: Activation of cyclo-oxygenase-2 contributes to motor and cognitive dysfunction following diffuse traumatic brain injury in rats
Author: Cernak, I.
O'Connor, C.
Vink, R.
Citation: Clinical and Experimental Pharmacology and Physiology, 2001; 28(11):922-925
Publisher: Blackwell Publishing Asia
Issue Date: 2001
ISSN: 0305-1870
Statement of
I Cernak, C O'Connor, R Vink
Abstract: 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.
Keywords: diffuse axonal injury; neurological outcome; neurotrauma; nimesulide
Description: The definitive version is available at Article first published online: 12 JAN 2002
Rights: Copyright © 2001 John Wiley & Sons, Inc. All Rights Reserved.
RMID: 0020071748
DOI: 10.1046/j.1440-1681.2001.03549
Appears in Collections:Anatomical Sciences publications

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