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Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Deletion of Nrf2 Exacerbates Oxidative Stress After Traumatic Brain Injury in Mice
Xin-Yu Lu1, Han-Dong Wang, Jian-Guo Xu
1Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
Abstract:
Traumatic brain injury (TBI) is a worldwide public health and medical problem. Oxidative stress is recognized as an important contributing factor in the pathogenesis of TBI. The present study was designed to explore the anti-oxidative effect of Nuclear factor erythroid 2-related factor 2 (Nrf2) on brain damage induced by traumatic injury in a mouse model. Moderate weight-drop impact head injury was induced in adult male mice. The mice were randomly divided into four groups: Nrf2(+/+) sham-operation, Nrf2(-/-) sham-operation, Nrf2(+/+) TBI, and Nrf2(-/-) TBI group. Neurological scores were evaluated 24 h after TBI, followed by collection of the brain specimens. Brain edema was detected by the wet-dry ratio method. The expression of NOX2 protein in the brain specimen was investigated using Western Blot analysis and immunohistochemical staining. In addition, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were evaluated in the brain tissues. Twenty-four hours after TBI, our results showed Nrf2(+/+) TBI mice have more severe neurological deficits and brain edema than Nrf2(+/+) sham group. On the other hand, the Nrf2(-/-) TBI mice were found to have significantly increased neurological deficits and brain edema, compared to Nrf2(+/+) TBI mice (P < 0.05). At the same time, we found that the expression of NOX2 protein, MDA level were significantly increased in Nrf2(-/-) mice, while SOD activity was considerably decreased after TBI compared to Nrf2(+/+) mice (P < 0.05). We demonstrated that deletion of Nrf2 exacerbates brain injury after TBI in mice, suggesting that Nrf2 may play an important role in protecting brain injury after TBI, possibly by modulating oxidative stress.
Insights
Nuclear factor erythroid 2-related factor 2 (Nrf2) deficiency worsens brain damage and oxidative stress after traumatic brain injury (TBI) in mice. Nrf2 plays a protective role in TBI by modulating oxidative stress.
Area of Science:
- Neuroscience
- Pathology
- Molecular Biology
Background:
- Traumatic brain injury (TBI) is a significant global health concern.
- Oxidative stress is a key factor in TBI pathogenesis.
- The role of Nuclear factor erythroid 2-related factor 2 (Nrf2) in TBI-induced brain damage requires further elucidation.
Purpose of the Study:
- To investigate the protective effect of Nrf2 against oxidative stress and brain damage following TBI.
- To analyze the impact of Nrf2 deletion on neurological deficits and brain edema in a mouse model of TBI.
Main Methods:
- Adult male mice with and without Nrf2 expression (Nrf2(+/+) and Nrf2(-/-)) were subjected to a controlled weight-drop TBI model.
- Neurological scores and brain edema (wet-dry ratio) were assessed 24 hours post-TBI.
- Western blot and immunohistochemistry were used to evaluate NOX2 protein expression.
- Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured in brain tissues.
Main Results:
- TBI induced more severe neurological deficits and brain edema in Nrf2(+/+) mice compared to sham controls.
- Nrf2(-/-) TBI mice exhibited significantly exacerbated neurological deficits and brain edema compared to Nrf2(+/+) TBI mice.
- Nrf2 deletion led to increased NOX2 protein and MDA levels, and decreased SOD activity post-TBI.
Conclusions:
- Nrf2 deficiency exacerbates brain injury and oxidative stress following TBI in mice.
- Nrf2 plays a critical neuroprotective role in TBI, likely through the modulation of oxidative stress pathways.
- Targeting Nrf2 may represent a therapeutic strategy for mitigating TBI-induced brain damage.
