PMID- 11703397
DA - 20011112
DCOM- 20011205
IS - 0305-1870
VI - 28
IP - 11
DP - 2001 Nov
TI - Activation of cyclo-oxygenase-2 contributes to motor and cognitive dysfunction following diffuse traumatic brain injury in rats.
PG - 922-5 AB - 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.
AD - Department of Physiology and Pharmacology, James Cook University,
[emd]
FAU - Cernak, I
AU - Cernak I
FAU - O'Connor, C
AU - O'Connor C
FAU - Vink, R
AU - Vink R
LA - eng
PT - Journal Article
CY - Australia
TA - Clin Exp Pharmacol Physiol
JID - 0425076
RN - 0 (Cyclooxygenase Inhibitors)
RN - 0 (Isoenzymes)
RN - 0 (Sulfonamides)
RN - 51803-78-2 (nimesulide)
RN - EC 1.14.99.- (cyclooxygenase 2)
RN - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthase)
SB - IM
MH - Animal
MH - Brain Injuries/complications/*enzymology/physiopathology
MH - Cognition Disorders/*enzymology/etiology/metabolism
MH - Cyclooxygenase Inhibitors/pharmacology
MH - Disease Models, Animal
MH - Enzyme Activation
MH - Isoenzymes/antagonists & inhibitors/*metabolism
MH - Male
MH - *Motor Activity/drug effects
MH - Prostaglandin-Endoperoxide Synthase/*metabolism
MH - Rats
MH - Rats, Sprague-Dawley
MH - Sulfonamides/pharmacology
MH - Support, Non-U.S. Gov't
EDAT- 2001/11/13 10:00
MHDA- 2002/01/05 10:01
AID - 3549 [pii]
PST - ppublish
SO - Clin Exp Pharmacol Physiol 2001 Nov;28(11):922-5.