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Delayed neuromotor recovery and increased memory acquisition dysfunction following experimental brain trauma in mice lacking the DNA repair gene XPA.

Tomasevic, Gregor LU ; Laurer, Helmut L; Mattiasson, Gustav LU ; Steeg, Harryvan; Wieloch, Tadeusz LU and McIntosh, Tracy K (2012) In Journal of Neurosurgery 116(6). p.1368-1378
Abstract
Object:

This study investigates the outcome after traumatic brain injury (TBI) in mice lacking the essential DNA repair gene xeroderma pigmentosum group A (XPA). As damage to DNA has been implicated in neuronal cell death in various models, the authors sought to elucidate whether the absence of an essential DNA repair factor would affect the outcome of TBI in an experimental setting.



Methods:

Thirty-seven adult mice of either wild-type (n = 18) or XPA-deficient ("knock-out" [n = 19]) genotype were subjected to controlled cortical impact experimental brain trauma, which produced a focal brain injury. Sham-injured mice of both genotypes were used as controls (9 in each group). The mice were subjected to... (More)
Object:

This study investigates the outcome after traumatic brain injury (TBI) in mice lacking the essential DNA repair gene xeroderma pigmentosum group A (XPA). As damage to DNA has been implicated in neuronal cell death in various models, the authors sought to elucidate whether the absence of an essential DNA repair factor would affect the outcome of TBI in an experimental setting.



Methods:

Thirty-seven adult mice of either wild-type (n = 18) or XPA-deficient ("knock-out" [n = 19]) genotype were subjected to controlled cortical impact experimental brain trauma, which produced a focal brain injury. Sham-injured mice of both genotypes were used as controls (9 in each group). The mice were subjected to neurobehavoral tests evaluating learning/acquisition (Morris water maze) and motor dysfunction (Rotarod and composite neuroscore test), pre- and postinjury up to 4 weeks. The mice were killed after 1 or 4 weeks, and cortical lesion volume, as well as hippocampal and thalamic cell loss, was evaluated. Hippocampal staining with doublecortin antibody was used to evaluate neurogenesis after the insult.



Results:

Brain-injured XPA(-/-) mice exhibited delayed recovery from impairment in neurological motor function, as well as pronounced cognitive dysfunction in a spatial learning task (Morris water maze), compared with injured XPA(+/+) mice (p < 0.05). No differences in cortical lesion volume, hippocampal damage, or thalamic cell loss were detected between XPA(+/+) and XPA(-/-) mice after brain injury. Also, no difference in the number of cells stained with doublecortin in the hippocampus was detected.



Conclusions:

The authors' results suggest that lack of the DNA repair factor XPA may delay neurobehavioral recovery after TBI, although they do not support the notion that this DNA repair deficiency results in increased cell or tissue death in the posttraumatic brain. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Neurosurgery
volume
116
issue
6
pages
1368 - 1378
publisher
American Association of Neurosurgeons
external identifiers
  • WOS:000304294000033
  • PMID:22462511
  • Scopus:84861967873
ISSN
0022-3085
DOI
10.3171/2012.2.JNS11888
language
English
LU publication?
yes
id
7f4404a4-902f-48c6-af60-0c7ff1abfe5d (old id 2520053)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22462511?dopt=Abstract
date added to LUP
2012-05-04 10:16:41
date last changed
2016-11-21 10:18:38
@misc{7f4404a4-902f-48c6-af60-0c7ff1abfe5d,
  abstract     = {Object:<br/><br>
This study investigates the outcome after traumatic brain injury (TBI) in mice lacking the essential DNA repair gene xeroderma pigmentosum group A (XPA). As damage to DNA has been implicated in neuronal cell death in various models, the authors sought to elucidate whether the absence of an essential DNA repair factor would affect the outcome of TBI in an experimental setting. <br/><br>
<br/><br>
Methods:<br/><br>
Thirty-seven adult mice of either wild-type (n = 18) or XPA-deficient ("knock-out" [n = 19]) genotype were subjected to controlled cortical impact experimental brain trauma, which produced a focal brain injury. Sham-injured mice of both genotypes were used as controls (9 in each group). The mice were subjected to neurobehavoral tests evaluating learning/acquisition (Morris water maze) and motor dysfunction (Rotarod and composite neuroscore test), pre- and postinjury up to 4 weeks. The mice were killed after 1 or 4 weeks, and cortical lesion volume, as well as hippocampal and thalamic cell loss, was evaluated. Hippocampal staining with doublecortin antibody was used to evaluate neurogenesis after the insult. <br/><br>
<br/><br>
Results:<br/><br>
Brain-injured XPA(-/-) mice exhibited delayed recovery from impairment in neurological motor function, as well as pronounced cognitive dysfunction in a spatial learning task (Morris water maze), compared with injured XPA(+/+) mice (p &lt; 0.05). No differences in cortical lesion volume, hippocampal damage, or thalamic cell loss were detected between XPA(+/+) and XPA(-/-) mice after brain injury. Also, no difference in the number of cells stained with doublecortin in the hippocampus was detected. <br/><br>
<br/><br>
Conclusions:<br/><br>
The authors' results suggest that lack of the DNA repair factor XPA may delay neurobehavioral recovery after TBI, although they do not support the notion that this DNA repair deficiency results in increased cell or tissue death in the posttraumatic brain.},
  author       = {Tomasevic, Gregor and Laurer, Helmut L and Mattiasson, Gustav and Steeg, Harryvan and Wieloch, Tadeusz and McIntosh, Tracy K},
  issn         = {0022-3085},
  language     = {eng},
  number       = {6},
  pages        = {1368--1378},
  publisher    = {ARRAY(0x4043a60)},
  series       = {Journal of Neurosurgery},
  title        = {Delayed neuromotor recovery and increased memory acquisition dysfunction following experimental brain trauma in mice lacking the DNA repair gene XPA.},
  url          = {http://dx.doi.org/10.3171/2012.2.JNS11888},
  volume       = {116},
  year         = {2012},
}