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Cyclooxygenase-2, prostaglandin synthases, and prostaglandin H2 metabolism in traumatic brain injury in the rat

Kunz, Tina; Marklund, Niklas LU ; Hillered, Lars and Oliw, Ernst H (2002) In Journal of Neurotrauma 19(9). p.64-1051
Abstract

Inflammatory mediators are important in traumatic brain injury (TBI). The objective of the present study was to investigate the expression of cyclooxygenase-2 (COX-2), prostaglandin E (PGE) and PGD synthases, and PGH2 metabolism in two rat models of TBI. Fluid percussion injury (FPI) resulted in bilateral induction of COX-2 mRNA in the dentate gyri and the cortex, whereas controlled cortical contusion injury (CCC) induced COX-2 mRNA in the ipsilateral dentate gyrus and intensely in the cortex as judged by in situ hybridization. The induction subsided within 24 h. COX-2 immunoreactivity was detectable in these areas and persisted in the ipsilateral cortex for at least 72 h after CCC. Regions with COX-2 induction co-localized with TUNEL... (More)

Inflammatory mediators are important in traumatic brain injury (TBI). The objective of the present study was to investigate the expression of cyclooxygenase-2 (COX-2), prostaglandin E (PGE) and PGD synthases, and PGH2 metabolism in two rat models of TBI. Fluid percussion injury (FPI) resulted in bilateral induction of COX-2 mRNA in the dentate gyri and the cortex, whereas controlled cortical contusion injury (CCC) induced COX-2 mRNA in the ipsilateral dentate gyrus and intensely in the cortex as judged by in situ hybridization. The induction subsided within 24 h. COX-2 immunoreactivity was detectable in these areas and persisted in the ipsilateral cortex for at least 72 h after CCC. Regions with COX-2 induction co-localized with TUNEL staining, suggesting a link between COX-2 expression and cell damage. COX-2 forms PGH2, which can be isomerized to PGD2, PGE2, and PGF2alpha by enzymatic and non-enzymatic mechanisms. In situ hybridization showed that mRNA of PGD synthase and microsomal PGE synthase were present in the choroid plexus. The microsomal PGE synthase was induced bilaterally after FPI and unilaterally after CCC. Liquid chromatography-mass spectrometry showed that low speed supernatant of normal and traumatized cortex and hippocampus transformed PGH2 to PGD2 as main product. PGD2 was dehydrated in brain homogenates to biological active compounds, for example, 15-deoxy-delta12,14-PGJ2. Thus COX-2 increases in certain neurons following TBI without neuronal induction of PGD and microsomal PGE synthases, suggesting that PGH2 may decompose to PGD2 and its dehydration products by nonenzymatic mechanisms or to PGD2 by low constitutive levels of PGD synthase.

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published
keywords
Animals, Apoptosis, Brain, Brain Chemistry, Brain Injuries, Cyclooxygenase 2, Enzyme Induction, Gene Expression Regulation, Enzymologic, Immunohistochemistry, In Situ Hybridization, In Situ Nick-End Labeling, Isoenzymes, Male, Mass Spectrometry, Prostaglandin H2, Prostaglandin-Endoperoxide Synthases, Prostaglandins H, RNA, Messenger, Rats, Time Factors, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Neurotrauma
volume
19
issue
9
pages
14 pages
publisher
Mary Ann Liebert, Inc.
external identifiers
  • scopus:0036737399
ISSN
0897-7151
DOI
10.1089/089771502760341965
language
English
LU publication?
no
id
f463fd4a-af60-4b3e-8ccb-3823f6af2fe7
date added to LUP
2018-03-01 11:34:37
date last changed
2018-10-07 05:04:51
@article{f463fd4a-af60-4b3e-8ccb-3823f6af2fe7,
  abstract     = {<p>Inflammatory mediators are important in traumatic brain injury (TBI). The objective of the present study was to investigate the expression of cyclooxygenase-2 (COX-2), prostaglandin E (PGE) and PGD synthases, and PGH2 metabolism in two rat models of TBI. Fluid percussion injury (FPI) resulted in bilateral induction of COX-2 mRNA in the dentate gyri and the cortex, whereas controlled cortical contusion injury (CCC) induced COX-2 mRNA in the ipsilateral dentate gyrus and intensely in the cortex as judged by in situ hybridization. The induction subsided within 24 h. COX-2 immunoreactivity was detectable in these areas and persisted in the ipsilateral cortex for at least 72 h after CCC. Regions with COX-2 induction co-localized with TUNEL staining, suggesting a link between COX-2 expression and cell damage. COX-2 forms PGH2, which can be isomerized to PGD2, PGE2, and PGF2alpha by enzymatic and non-enzymatic mechanisms. In situ hybridization showed that mRNA of PGD synthase and microsomal PGE synthase were present in the choroid plexus. The microsomal PGE synthase was induced bilaterally after FPI and unilaterally after CCC. Liquid chromatography-mass spectrometry showed that low speed supernatant of normal and traumatized cortex and hippocampus transformed PGH2 to PGD2 as main product. PGD2 was dehydrated in brain homogenates to biological active compounds, for example, 15-deoxy-delta12,14-PGJ2. Thus COX-2 increases in certain neurons following TBI without neuronal induction of PGD and microsomal PGE synthases, suggesting that PGH2 may decompose to PGD2 and its dehydration products by nonenzymatic mechanisms or to PGD2 by low constitutive levels of PGD synthase.</p>},
  author       = {Kunz, Tina and Marklund, Niklas and Hillered, Lars and Oliw, Ernst H},
  issn         = {0897-7151},
  keyword      = {Animals,Apoptosis,Brain,Brain Chemistry,Brain Injuries,Cyclooxygenase 2,Enzyme Induction,Gene Expression Regulation, Enzymologic,Immunohistochemistry,In Situ Hybridization,In Situ Nick-End Labeling,Isoenzymes,Male,Mass Spectrometry,Prostaglandin H2,Prostaglandin-Endoperoxide Synthases,Prostaglandins H,RNA, Messenger,Rats,Time Factors,Comparative Study,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {9},
  pages        = {64--1051},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Journal of Neurotrauma},
  title        = {Cyclooxygenase-2, prostaglandin synthases, and prostaglandin H2 metabolism in traumatic brain injury in the rat},
  url          = {http://dx.doi.org/10.1089/089771502760341965},
  volume       = {19},
  year         = {2002},
}