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Free radical scavenger posttreatment improves functional and morphological outcome after fluid percussion injury in the rat

Marklund, N LU ; Clausen, F; McIntosh, T K and Hillered, L (2001) In Journal of Neurotrauma 18(8). p.32-821
Abstract

Reactive oxygen species (ROS) are thought to contribute to the secondary injury process after traumatic brain injury (TBI). ROS scavenging compounds have shown neuroprotective properties in various models of experimental brain injury, including TBI. Administration of nitrone radical scavengers has emerged as a promising pharmacological concept in focal experimental ischemia due to their low toxicity and neuroprotective properties, with a time window of several hours. The aim of this study was to test the neuroprotective efficacy of two nitrones, the readily blood-brain barrier (BBB) penetrating alpha-phenyl-N-tert-butyl nitrone (PBN) and the poorly BBB penetrating sulfo-derivative, 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) after... (More)

Reactive oxygen species (ROS) are thought to contribute to the secondary injury process after traumatic brain injury (TBI). ROS scavenging compounds have shown neuroprotective properties in various models of experimental brain injury, including TBI. Administration of nitrone radical scavengers has emerged as a promising pharmacological concept in focal experimental ischemia due to their low toxicity and neuroprotective properties, with a time window of several hours. The aim of this study was to test the neuroprotective efficacy of two nitrones, the readily blood-brain barrier (BBB) penetrating alpha-phenyl-N-tert-butyl nitrone (PBN) and the poorly BBB penetrating sulfo-derivative, 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) after moderate (2.20-2.45 atm) lateral fluid percussion injury (FPI) in rats. Twenty-six rats received a 24-h intravenous infusion (30 mg/kg/h) of saline, PBN, or an equimolar dose of S-PBN beginning 30 min after FPI. Eight sham-operated animals were used as controls. Cognitive function was assessed using the Morris Water Maze at day 11-15 after TBI, neurological status at day 1, 4, and 8 and morphological outcome at day 15. PBN and S-PBN treatment significantly reduced the loss of ipsilateral hemispheric tissue whereas only S-PBN tended to reduce the cortical lesion volume. PBN treatment caused a significant improvement in the neurological score as compared to saline-treated animals, while S-PBN alone attenuated the cognitive deficit. Our results suggest that nitrone radical scavengers are neuroprotective when administered 30 min after FPI in rats. Differences in pharmacokinetics may account for the observed individual neuroprotective profiles of the two nitrones.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Brain Injuries, Cyclic N-Oxides, Free Radical Scavengers, Infusions, Intravenous, Male, Maze Learning, Memory Disorders, Neuroprotective Agents, Nitrogen Oxides, Rats, Rats, Sprague-Dawley, Reactive Oxygen Species, Recovery of Function, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Neurotrauma
volume
18
issue
8
pages
12 pages
publisher
Mary Ann Liebert, Inc.
external identifiers
  • scopus:0034883444
ISSN
0897-7151
DOI
10.1089/089771501316919184
language
English
LU publication?
no
id
1c8af49c-87f7-4e8e-aa5a-369aea9cb51c
date added to LUP
2016-12-08 12:15:39
date last changed
2018-02-04 04:24:40
@article{1c8af49c-87f7-4e8e-aa5a-369aea9cb51c,
  abstract     = {<p>Reactive oxygen species (ROS) are thought to contribute to the secondary injury process after traumatic brain injury (TBI). ROS scavenging compounds have shown neuroprotective properties in various models of experimental brain injury, including TBI. Administration of nitrone radical scavengers has emerged as a promising pharmacological concept in focal experimental ischemia due to their low toxicity and neuroprotective properties, with a time window of several hours. The aim of this study was to test the neuroprotective efficacy of two nitrones, the readily blood-brain barrier (BBB) penetrating alpha-phenyl-N-tert-butyl nitrone (PBN) and the poorly BBB penetrating sulfo-derivative, 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) after moderate (2.20-2.45 atm) lateral fluid percussion injury (FPI) in rats. Twenty-six rats received a 24-h intravenous infusion (30 mg/kg/h) of saline, PBN, or an equimolar dose of S-PBN beginning 30 min after FPI. Eight sham-operated animals were used as controls. Cognitive function was assessed using the Morris Water Maze at day 11-15 after TBI, neurological status at day 1, 4, and 8 and morphological outcome at day 15. PBN and S-PBN treatment significantly reduced the loss of ipsilateral hemispheric tissue whereas only S-PBN tended to reduce the cortical lesion volume. PBN treatment caused a significant improvement in the neurological score as compared to saline-treated animals, while S-PBN alone attenuated the cognitive deficit. Our results suggest that nitrone radical scavengers are neuroprotective when administered 30 min after FPI in rats. Differences in pharmacokinetics may account for the observed individual neuroprotective profiles of the two nitrones.</p>},
  author       = {Marklund, N and Clausen, F and McIntosh, T K and Hillered, L},
  issn         = {0897-7151},
  keyword      = {Animals,Brain Injuries,Cyclic N-Oxides,Free Radical Scavengers,Infusions, Intravenous,Male,Maze Learning,Memory Disorders,Neuroprotective Agents,Nitrogen Oxides,Rats,Rats, Sprague-Dawley,Reactive Oxygen Species,Recovery of Function,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {8},
  pages        = {32--821},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Journal of Neurotrauma},
  title        = {Free radical scavenger posttreatment improves functional and morphological outcome after fluid percussion injury in the rat},
  url          = {http://dx.doi.org/10.1089/089771501316919184},
  volume       = {18},
  year         = {2001},
}