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Updated: Jun 26, 2026
Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice
Published on: September 28, 2022
Role of Nrf2 in protection against traumatic brain injury in mice
Wei Jin1, Handong Wang, Wei Yan
1Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
Abstract:
Previous studies have shown that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a unique role in many physiological stress processes. The present study investigated the role of Nrf2 in modulating traumatic brain injury (TBI)-induced secondary brain injury. Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact head injury. The absence of Nrf2 function in mice resulted in exacerbated brain injury as shown by the increased severity of neurological deficit, apoptosis, and brain edema at 24h after TBI. This exacerbation of brain injury in Nrf2-deficient mice was associated with increased mRNA and protein expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), and with decreased mRNA expression and enzymatic activity of antioxidant and detoxifying enzymes including NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase alpha-1 (GST-alpha1), compared with their wild-type counterparts after TBI. In combination, these results suggest that Nrf2 plays an important role in protecting TBI-induced secondary brain injury, possibly by regulating inflammatory cytokines and inducing antioxidant and detoxifying enzymes.
Insights
Nuclear factor erythroid 2-related factor 2 (Nrf2) deficiency worsens traumatic brain injury (TBI) outcomes. Nrf2 protects against TBI by reducing inflammation and boosting antioxidant defenses.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Nuclear factor erythroid 2-related factor 2 (Nrf2) is crucial in cellular stress responses.
- Traumatic brain injury (TBI) involves complex secondary injury mechanisms.
- The specific role of Nrf2 in TBI-induced secondary injury requires further elucidation.
Purpose of the Study:
- To investigate the role of Nrf2 in modulating secondary brain injury following TBI.
- To determine the impact of Nrf2 deficiency on TBI-induced neuropathology and molecular responses.
Main Methods:
- Utilized a weight-drop impact model of TBI in wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice.
- Assessed neurological deficit, apoptosis, and brain edema at 24 hours post-TBI.
- Quantified mRNA and protein expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and antioxidant enzymes (NQO1, GST-α1).
Main Results:
- Nrf2 deficiency exacerbated TBI, leading to increased neurological deficits, apoptosis, and brain edema.
- Absence of Nrf2 elevated inflammatory cytokine expression (TNF-α, IL-1β, IL-6) post-TBI.
- Nrf2 deficiency decreased the expression and activity of antioxidant enzymes (NQO1, GST-α1) after TBI.
Conclusions:
- Nrf2 plays a significant protective role in mitigating secondary brain injury after TBI.
- Nrf2 likely exerts its protective effects by downregulating inflammatory responses and upregulating antioxidant defenses.
- Targeting Nrf2 may represent a therapeutic strategy for managing TBI.
