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Updated: Feb 12, 2026
Induction of Diffuse Axonal Brain Injury in Rats Based on Rotational Acceleration
Published on: May 9, 2020
Curcumin mitigates axonal injury and neuronal cell apoptosis through the PERK/Nrf2 signaling pathway following
Tingqin Huang1, Junjie Zhao, Dan Guo
1Department of Neurosurgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
Abstract:
Diffuse axonal injury (DAI) accounts for more than 50% of all traumatic brain injury. In response to the mechanical damage associated with DAI, the abnormal proteins produced in the neurons and axons, namely, β-APP and p-tau, induce endoplasmic reticulum (ER) stress. Curcumin, a major component extracted from the rhizome of Curcuma longa, has shown potent anti-inflammatory, antioxidant, anti-infection, and antitumor activity in previous studies. Moreover, curcumin is an activator of nuclear factor-erythroid 2-related factor 2 (Nrf2) and promotes its nuclear translocation. In this study, we evaluated the therapeutic potential of curcumin for the treatment of DAI and investigated the mechanisms underlying the protective effects of curcumin against neural cell death and axonal injury after DAI. Rats subjected to a model of DAI by head rotational acceleration were treated with vehicle or curcumin to evaluate the effect of curcumin on neuronal and axonal injury. We observed that curcumin (20 mg/kg intraperitoneal) administered 1 h after DAI induction alleviated the aggregation of p-tau and β-APP in neurons, reduced ER-stress-related cell apoptosis, and ameliorated neurological deficits. Further investigation showed that the protective effect of curcumin in DAI was mediated by the PERK/Nrf2 pathway. Curcumin promoted PERK phosphorylation, and then Nrf2 dissociated from Keap1 and was translocated to the nucleus, which activated ATF4, an important bZIP transcription factor that maintains intracellular homeostasis, but inhibited the CHOP, a hallmark of ER stress and ER-associated programmed cell death. In summary, we demonstrate for the first time that curcumin confers protection against abnormal proteins and neuronal apoptosis after DAI, that the process is mediated by strengthening of the unfolded protein response to overcome ER stress, and that the protective effect of curcumin against DAI is dependent on the activation of Nrf2.
Insights
Curcumin, a natural compound, protects against diffuse axonal injury (DAI) by reducing abnormal protein buildup and neuronal apoptosis. Its therapeutic effects are linked to activating the Nrf2 pathway and managing endoplasmic reticulum stress.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Diffuse axonal injury (DAI) is a major cause of traumatic brain injury, leading to abnormal protein accumulation (β-APP, p-tau) and endoplasmic reticulum (ER) stress.
- Curcumin, derived from Curcuma longa, exhibits anti-inflammatory and antioxidant properties and activates the Nrf2 pathway.
Purpose of the Study:
- To evaluate curcumin's therapeutic potential for DAI.
- To investigate the mechanisms behind curcumin's protective effects against neuronal cell death and axonal injury in DAI.
Main Methods:
- A rat model of DAI was established using head rotational acceleration.
- Rats were treated with vehicle or curcumin (20 mg/kg) intraperitoneally 1 hour after DAI induction.
- Neuronal and axonal injury, protein aggregation, ER stress markers, and neurological deficits were assessed.
Main Results:
- Curcumin treatment alleviated p-tau and β-APP aggregation, reduced ER-stress-induced apoptosis, and improved neurological function.
- Curcumin activated the PERK/Nrf2 pathway, leading to Nrf2 nuclear translocation.
- This activation promoted ATF4 and inhibited CHOP, mitigating ER stress and cell death.
Conclusions:
- Curcumin offers protection against abnormal protein accumulation and neuronal apoptosis in DAI.
- The protective mechanism involves enhancing the unfolded protein response to overcome ER stress.
- Curcumin's efficacy in DAI is dependent on Nrf2 pathway activation.
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