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Effect of traumatic brain injury and nitrone radical scavengers on relative changes in regional cerebral blood flow and glucose uptake in rats

Marklund, Niklas LU ; Sihver, Sven; Långström, Bengt; Bergström, Mats and Hillered, Lars (2002) In Journal of Neurotrauma 19(10). p.53-1139
Abstract

Changes in regional cerebral blood flow (rCBF) and glucose metabolism are commonly associated with traumatic brain injury (TBI). Reactive oxygen species (ROS) have been implicated as key contributors to the secondary injury process after TBI. Here, pretreatment with the nitrone radical scavengers (alpha-phenyl-N-tert-butyl nitrone (PBN) or its sulfonated analogue sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) were used as tools to study the effects of ROS on rCBF and glucose metabolism after moderate (2.4-2.6 atm) lateral fluid percussion injury (FPI) in rats. S-PBN has a half-life in plasma of 9 min and does not penetrate the blood-brain barrier (BBB). In contrast, PBN has a half-life of 3 h and readily penetrates the BBB. Regional... (More)

Changes in regional cerebral blood flow (rCBF) and glucose metabolism are commonly associated with traumatic brain injury (TBI). Reactive oxygen species (ROS) have been implicated as key contributors to the secondary injury process after TBI. Here, pretreatment with the nitrone radical scavengers (alpha-phenyl-N-tert-butyl nitrone (PBN) or its sulfonated analogue sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) were used as tools to study the effects of ROS on rCBF and glucose metabolism after moderate (2.4-2.6 atm) lateral fluid percussion injury (FPI) in rats. S-PBN has a half-life in plasma of 9 min and does not penetrate the blood-brain barrier (BBB). In contrast, PBN has a half-life of 3 h and readily penetrates the BBB. Regional cerebral blood flow (rCBF) and glucose metabolism was estimated by using (99m)Tc-HMPAO and [(18)F]Fluoro-2-deoxyglucose (FDG) autoradiography, respectively, at 42 min (n = 37) and 12 h (n = 34) after the injury. Regions of interest were the parietal cortex and hippocampus bilaterally. As expected, FPI produced an early (42-min) hypoperfusion in ipsilateral cortex and an increase in glucose metabolism in both cortex and hippocampus, giving way to a state of hypoperfusion and decreased glucose metabolism at 12 h postinjury. On the contralateral side, a hypoperfusion in the cortex and hippocampus was seen at 12 h only, but no significant changes in glucose metabolism. Both S-PBN and PBN attenuated the trauma-induced changes in rCBF and glucose metabolism. Thus, the early improvement in rCBF and glucose metabolism correlates with and may partly mediate the improved functional and morphological outcome after TBI in nitrone-treated rats.

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Contribution to journal
publication status
published
keywords
Animals, Benzenesulfonates, Brain Injuries, Cerebrovascular Circulation, Cyclic N-Oxides, Fluorodeoxyglucose F18, Free Radical Scavengers, Glucose, Hippocampus, Male, Neuroprotective Agents, Nitrogen Oxides, Radiopharmaceuticals, Rats, Rats, Sprague-Dawley, Reactive Oxygen Species, Technetium Tc 99m Exametazime, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Neurotrauma
volume
19
issue
10
pages
15 pages
publisher
Mary Ann Liebert, Inc.
external identifiers
  • scopus:0036800136
ISSN
0897-7151
DOI
10.1089/08977150260337958
language
English
LU publication?
no
id
f476d972-e2ea-40d9-834f-c3cd9805e8a7
date added to LUP
2016-12-08 12:16:31
date last changed
2017-10-01 05:27:17
@article{f476d972-e2ea-40d9-834f-c3cd9805e8a7,
  abstract     = {<p>Changes in regional cerebral blood flow (rCBF) and glucose metabolism are commonly associated with traumatic brain injury (TBI). Reactive oxygen species (ROS) have been implicated as key contributors to the secondary injury process after TBI. Here, pretreatment with the nitrone radical scavengers (alpha-phenyl-N-tert-butyl nitrone (PBN) or its sulfonated analogue sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) were used as tools to study the effects of ROS on rCBF and glucose metabolism after moderate (2.4-2.6 atm) lateral fluid percussion injury (FPI) in rats. S-PBN has a half-life in plasma of 9 min and does not penetrate the blood-brain barrier (BBB). In contrast, PBN has a half-life of 3 h and readily penetrates the BBB. Regional cerebral blood flow (rCBF) and glucose metabolism was estimated by using (99m)Tc-HMPAO and [(18)F]Fluoro-2-deoxyglucose (FDG) autoradiography, respectively, at 42 min (n = 37) and 12 h (n = 34) after the injury. Regions of interest were the parietal cortex and hippocampus bilaterally. As expected, FPI produced an early (42-min) hypoperfusion in ipsilateral cortex and an increase in glucose metabolism in both cortex and hippocampus, giving way to a state of hypoperfusion and decreased glucose metabolism at 12 h postinjury. On the contralateral side, a hypoperfusion in the cortex and hippocampus was seen at 12 h only, but no significant changes in glucose metabolism. Both S-PBN and PBN attenuated the trauma-induced changes in rCBF and glucose metabolism. Thus, the early improvement in rCBF and glucose metabolism correlates with and may partly mediate the improved functional and morphological outcome after TBI in nitrone-treated rats.</p>},
  author       = {Marklund, Niklas and Sihver, Sven and Långström, Bengt and Bergström, Mats and Hillered, Lars},
  issn         = {0897-7151},
  keyword      = {Animals,Benzenesulfonates,Brain Injuries,Cerebrovascular Circulation,Cyclic N-Oxides,Fluorodeoxyglucose F18,Free Radical Scavengers,Glucose,Hippocampus,Male,Neuroprotective Agents,Nitrogen Oxides,Radiopharmaceuticals,Rats,Rats, Sprague-Dawley,Reactive Oxygen Species,Technetium Tc 99m Exametazime,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {10},
  pages        = {53--1139},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Journal of Neurotrauma},
  title        = {Effect of traumatic brain injury and nitrone radical scavengers on relative changes in regional cerebral blood flow and glucose uptake in rats},
  url          = {http://dx.doi.org/10.1089/08977150260337958},
  volume       = {19},
  year         = {2002},
}