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Paradoxical increase in neuronal DNA fragmentation after neuroprotective free radical scavenger treatment in experimental traumatic brain injury

Lewén, A; Skoglösa, Y; Clausen, F; Marklund, N LU ; Chan, P H; Lindholm, D and Hillered, L (2001) In Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 21(4). p.50-344
Abstract

The mechanisms and role of nerve cell death after traumatic brain injury (TBI) are not fully understood. The authors investigated the effect of pretreatment with the oxygen free radical spin trap alpha-phenyl-N-tert-butyl-nitrone (PBN) on the number of neurons undergoing apoptosis after TBI in rats. Apoptotic cells were identified by the TUNEL method combined with the nuclear stain, Hoechst 33258, and immunohistochemistry for the active form of caspase-3. Numerous neurons became positive for activated caspase 3 and TUNEL in the cortex at 24 hours after injury, suggesting ongoing biochemical apoptosis. In PBN-treated rats, a significantly greater number of cells were found to be TUNEL positive at 24 hours compared with controls. However,... (More)

The mechanisms and role of nerve cell death after traumatic brain injury (TBI) are not fully understood. The authors investigated the effect of pretreatment with the oxygen free radical spin trap alpha-phenyl-N-tert-butyl-nitrone (PBN) on the number of neurons undergoing apoptosis after TBI in rats. Apoptotic cells were identified by the TUNEL method combined with the nuclear stain, Hoechst 33258, and immunohistochemistry for the active form of caspase-3. Numerous neurons became positive for activated caspase 3 and TUNEL in the cortex at 24 hours after injury, suggesting ongoing biochemical apoptosis. In PBN-treated rats, a significantly greater number of cells were found to be TUNEL positive at 24 hours compared with controls. However, PBN treatment resulted in a reduced cortical lesion volume and improved behavioral outcome two weeks after injury. The authors conclude that a treatment producing an increase in DNA fragmentation in the early phase may be compatible with an overall beneficial effect on outcome after TBI. This should be considered in the screening process for future neuroprotective remedies.

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publishing date
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Contribution to journal
publication status
published
keywords
Animals, Apoptosis, Behavior, Animal, Brain Injuries, Caspase 3, Caspases, Cyclic N-Oxides, DNA Fragmentation, Free Radical Scavengers, In Situ Nick-End Labeling, Male, Necrosis, Neurons, Neuroprotective Agents, Nitrogen Oxides, Rats, Rats, Sprague-Dawley, Treatment Outcome, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
volume
21
issue
4
pages
7 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:0035053188
ISSN
0271-678X
DOI
10.1097/00004647-200104000-00003
language
English
LU publication?
no
id
d1c343db-7268-4a14-8d00-00e0778b9089
date added to LUP
2018-03-01 10:46:23
date last changed
2018-03-04 05:09:06
@article{d1c343db-7268-4a14-8d00-00e0778b9089,
  abstract     = {<p>The mechanisms and role of nerve cell death after traumatic brain injury (TBI) are not fully understood. The authors investigated the effect of pretreatment with the oxygen free radical spin trap alpha-phenyl-N-tert-butyl-nitrone (PBN) on the number of neurons undergoing apoptosis after TBI in rats. Apoptotic cells were identified by the TUNEL method combined with the nuclear stain, Hoechst 33258, and immunohistochemistry for the active form of caspase-3. Numerous neurons became positive for activated caspase 3 and TUNEL in the cortex at 24 hours after injury, suggesting ongoing biochemical apoptosis. In PBN-treated rats, a significantly greater number of cells were found to be TUNEL positive at 24 hours compared with controls. However, PBN treatment resulted in a reduced cortical lesion volume and improved behavioral outcome two weeks after injury. The authors conclude that a treatment producing an increase in DNA fragmentation in the early phase may be compatible with an overall beneficial effect on outcome after TBI. This should be considered in the screening process for future neuroprotective remedies.</p>},
  author       = {Lewén, A and Skoglösa, Y and Clausen, F and Marklund, N and Chan, P H and Lindholm, D and Hillered, L},
  issn         = {0271-678X},
  keyword      = {Animals,Apoptosis,Behavior, Animal,Brain Injuries,Caspase 3,Caspases,Cyclic N-Oxides,DNA Fragmentation,Free Radical Scavengers,In Situ Nick-End Labeling,Male,Necrosis,Neurons,Neuroprotective Agents,Nitrogen Oxides,Rats,Rats, Sprague-Dawley,Treatment Outcome,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {4},
  pages        = {50--344},
  publisher    = {Nature Publishing Group},
  series       = {Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism},
  title        = {Paradoxical increase in neuronal DNA fragmentation after neuroprotective free radical scavenger treatment in experimental traumatic brain injury},
  url          = {http://dx.doi.org/10.1097/00004647-200104000-00003},
  volume       = {21},
  year         = {2001},
}