Effects of the selective cyclooxygenase-2 inhibitor rofecoxib on cell death following traumatic brain injury in the rat
(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
- Kunz, Tina ; Marklund, Niklas LU ; Hillered, Lars and Oliw, Ernst H
- publishing date
- 2006
- 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
- 2024-09-17 17:12:33
@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}}, }