Genetic disruption of cyclooxygenase-2 does not improve histological or behavioral outcome after traumatic brain injury in mice.
Increasing evidence suggests a role for cyclooxygenase-2 (COX-2) in traumatic brain injury (TBI). In the present study, the role of COX-2 in TBI was investigated using COX-2 gene-disrupted (COX-2 null) mice and wild-type (WT) controls that were subjected to the controlled cortical impact (CCI) model of TBI. There was increased expression of COX-2 in ipsilateral hippocampus in WT mice subjected to CCI. CCI resulted in a significant increase in prostaglandin E(2) concentrations in WT compared with COX-2 null hippocampi. There was a significant increase in TUNEL staining of CA1 neurons 24 hr after CCI in WT, but not in COX-2 null mice, compared with sham-operated controls, which is consistent with a protective role for COX-2 in the early phase of injury after TBI. However, there was no difference in lesion volume 21 days after CCI in COX-2 null and WT mice. COX-2 gene disruption did not alter Morris water maze performance. Taken together, these results suggest only a minor role for COX-2 activity in determining outcome after TBI in mouse.
Ahmad
Muzamil
M
Geriatric Research Educational and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA 15206, USA.
Rose
Marie E
ME
Vagni
Vincent
V
Griffith
Raymond P
RP
Dixon
C Edward
CE
Kochanek
Patrick M
PM
Hickey
Robert W
RW
Graham
Steven H
SH
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001522:Behavior, Animal / Q000502:physiology; D001930:Brain Injuries / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000235:genetics*; D019610:Cytoprotection / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004660:Encephalitis / Q000201:enzymology* / Q000235:genetics* / Q000628:therapy; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics
C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone