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Effects of the selective cyclooxygenase-2 inhibitor rofecoxib on cell death following traumatic brain injury in the rat

Kunz, Tina ; Marklund, Niklas LU orcid ; Hillered, Lars and Oliw, Ernst H (2006) In Restorative Neurology and Neuroscience 24(1). p.55-63
Abstract

PURPOSE: Lateral fluid percussion brain injury (FPI) increases cyclooxygenase-2 (COX-2) expression in the cortex and hippocampus. The objective was to investigate whether the selective COX-2 inhibitor rofecoxib (10 mg/kg twice daily) reduces neuronal cell death after FPI in rats, since rofecoxib has been shown to be neuroprotective in other models of CNS injury.

METHODS: Rofecoxib (n = 23) or vehicle (n = 20) were administered after FPI and for up to 3 days. Cell death was evaluated by Fluoro-Jade B staining and by the TdT-mediated dUTP nick end labelling (TUNEL) assay.

RESULTS: COX-2 immunoreactivity increased in the ipsilateral cortex and hippocampus (CA1) and bilaterally in the dentate gyri. Fluoro-Jade B- and... (More)

PURPOSE: Lateral fluid percussion brain injury (FPI) increases cyclooxygenase-2 (COX-2) expression in the cortex and hippocampus. The objective was to investigate whether the selective COX-2 inhibitor rofecoxib (10 mg/kg twice daily) reduces neuronal cell death after FPI in rats, since rofecoxib has been shown to be neuroprotective in other models of CNS injury.

METHODS: Rofecoxib (n = 23) or vehicle (n = 20) were administered after FPI and for up to 3 days. Cell death was evaluated by Fluoro-Jade B staining and by the TdT-mediated dUTP nick end labelling (TUNEL) assay.

RESULTS: COX-2 immunoreactivity increased in the ipsilateral cortex and hippocampus (CA1) and bilaterally in the dentate gyri. Fluoro-Jade B- and TUNEL-positive cells were detected 12-72 h after FPI in the ipsilateral cortex and bilaterally in the dentate gyri. Fluoro-Jade B staining did not indicate a significant neuroprotective effect of rofecoxib (12-72 h) and neither did TUNEL staining. Quantificaton of the TUNEL staining in the ipsilateral cortex was approximately 50% lower in the rofecoxib group at 12 and 24 h, but this did not reach statistical significance (p = 0.06), and appeared unchanged at 72 h.

CONCLUSIONS: Rofecoxib lacked significant protective effect on early neuronal cell death in the FPI model of traumatic brain injury.

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author
; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Brain Injuries, Cell Count, Cell Death, Cyclooxygenase 2 Inhibitors, Disease Models, Animal, Fluoresceins, Hippocampus, Immunohistochemistry, In Situ Nick-End Labeling, Lactones, Male, Neurons, Organic Chemicals, Rats, Rats, Sprague-Dawley, Statistics, Nonparametric, Sulfones, Time Factors, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
in
Restorative Neurology and Neuroscience
volume
24
issue
1
pages
55 - 63
publisher
IOS Press
external identifiers
  • pmid:16518028
  • scopus:33644608758
ISSN
0922-6028
language
English
LU publication?
no
id
43cb71f5-955a-4032-9eb8-9ac686843383
date added to LUP
2018-03-03 14:21:36
date last changed
2024-04-15 02:59:40
@article{43cb71f5-955a-4032-9eb8-9ac686843383,
  abstract     = {{<p>PURPOSE: Lateral fluid percussion brain injury (FPI) increases cyclooxygenase-2 (COX-2) expression in the cortex and hippocampus. The objective was to investigate whether the selective COX-2 inhibitor rofecoxib (10 mg/kg twice daily) reduces neuronal cell death after FPI in rats, since rofecoxib has been shown to be neuroprotective in other models of CNS injury.</p><p>METHODS: Rofecoxib (n = 23) or vehicle (n = 20) were administered after FPI and for up to 3 days. Cell death was evaluated by Fluoro-Jade B staining and by the TdT-mediated dUTP nick end labelling (TUNEL) assay.</p><p>RESULTS: COX-2 immunoreactivity increased in the ipsilateral cortex and hippocampus (CA1) and bilaterally in the dentate gyri. Fluoro-Jade B- and TUNEL-positive cells were detected 12-72 h after FPI in the ipsilateral cortex and bilaterally in the dentate gyri. Fluoro-Jade B staining did not indicate a significant neuroprotective effect of rofecoxib (12-72 h) and neither did TUNEL staining. Quantificaton of the TUNEL staining in the ipsilateral cortex was approximately 50% lower in the rofecoxib group at 12 and 24 h, but this did not reach statistical significance (p = 0.06), and appeared unchanged at 72 h.</p><p>CONCLUSIONS: Rofecoxib lacked significant protective effect on early neuronal cell death in the FPI model of traumatic brain injury.</p>}},
  author       = {{Kunz, Tina and Marklund, Niklas and Hillered, Lars and Oliw, Ernst H}},
  issn         = {{0922-6028}},
  keywords     = {{Animals; Brain Injuries; Cell Count; Cell Death; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Fluoresceins; Hippocampus; Immunohistochemistry; In Situ Nick-End Labeling; Lactones; Male; Neurons; Organic Chemicals; Rats; Rats, Sprague-Dawley; Statistics, Nonparametric; Sulfones; Time Factors; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{55--63}},
  publisher    = {{IOS Press}},
  series       = {{Restorative Neurology and Neuroscience}},
  title        = {{Effects of the selective cyclooxygenase-2 inhibitor rofecoxib on cell death following traumatic brain injury in the rat}},
  volume       = {{24}},
  year         = {{2006}},
}