Related Experiment Video
Updated: May 23, 2026
A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome
Published on: May 22, 2019
Delayed neuromotor recovery and increased memory acquisition dysfunction following experimental brain trauma in mice
Gregor Tomasevic1, Helmut L Laurer, Gustav Mattiasson
1Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, Lund, Sweden. gregor.tomasevic@med.lu.se
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.
Insights
Mice lacking the DNA repair gene xeroderma pigmentosum A (XPA) showed delayed motor and cognitive recovery after traumatic brain injury (TBI). However, XPA deficiency did not increase brain tissue damage or cell death post-TBI.
Area of Science:
- Neuroscience
- Genetics
- Traumatic Brain Injury Research
Background:
- DNA damage is implicated in neuronal cell death following brain injury.
- The role of specific DNA repair pathways in TBI outcomes remains unclear.
Purpose of the Study:
- To investigate the impact of lacking the DNA repair gene xeroderma pigmentosum A (XPA) on outcomes after experimental traumatic brain injury (TBI).
- To determine if XPA deficiency influences neurobehavioral recovery, lesion volume, and cell loss post-TBI.
Main Methods:
- Controlled cortical impact TBI was induced in wild-type and XPA-deficient mice.
- Neurobehavioral tests (Morris water maze, Rotarod) assessed motor and cognitive function up to 4 weeks post-TBI.
- Histological analysis evaluated cortical lesion volume, hippocampal/thalamic cell loss, and neurogenesis.
Main Results:
- XPA-deficient mice exhibited significantly delayed recovery in motor function and spatial learning compared to wild-type mice (p < 0.05).
- No significant differences were observed in cortical lesion volume, hippocampal damage, or thalamic cell loss between genotypes.
- Neurogenesis, assessed by doublecortin staining, did not differ between XPA-deficient and wild-type mice post-TBI.
Conclusions:
- The absence of the DNA repair factor XPA may impede neurobehavioral recovery following TBI.
- XPA deficiency does not appear to exacerbate acute tissue damage or neuronal cell death in the post-TBI brain.
- These findings highlight a dissociation between neurobehavioral recovery and structural damage in TBI, influenced by DNA repair capacity.
