Neuroprotective effects of mild hypothermia against traumatic brain injury by the involvement of the Nrf2/ARE pathway.

Abstract

BACKGROUND:

Traumatic brain injury (TBI) is the leading cause of death and disability worldwide. Mild hypothermia (32-35°C) has been found to show neuroprotective effects against TBI. However, the specific mechanism is still elusive. In the current study, we explored the relationship between oxidative damage after TBI and treatment with mild hypothermia as well as the underlying molecular mechanisms.

METHODS:

We used the closed cortex injury model to perform the brain injury and a temperature monitoring and control system to regulate the body temperature of mice after injury. Adult male C57BL/6 mice were adopted in this study and divided into four experimental groups. Tissue samples were harvested 24 h after injury.

RESULTS:

First, our results showed that treatment with mild hypothermia significantly improved neurobehavioral dysfunction and alleviated brain edema after TBI. Moreover, treatment with mild hypothermia enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase and reduced the accumulation of lipid peroxidation malondialdehyde. Importantly, the expression and activation of the nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) pathway were upregulated by mild hypothermia after TBI. Finally, treatment with hypothermia significantly decreased the cell apoptosis induced by TBI.

CONCLUSION:

Our results showed that the protective effects of mild hypothermia after TBI may be achieved by the upregulation of the Nrf2-ARE pathway and revealed Nrf2 as a potentially important target to improve the prognosis of TBI.

• Authors: Chaolong Yan, Jiannan Mao, Chenbei Yao, Yang Liu, Huiying Yan, Wei Jin
• Journal: Brain and behavior (Brain Behav) Vol. 12 Issue 8 Pg. e2686 (08 2022) ISSN: 2162-3279 [Electronic] United States
• PMID: 35803901 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.

Chemical References

• NF-E2-Related Factor 2

Topics

• Animals
• Brain Injuries, Traumatic (metabolism, therapy)
• Disease Models, Animal
• Hypothermia
• Male
• Mice
• Mice, Inbred C57BL
• NF-E2-Related Factor 2 (metabolism)
• Neuroprotection
• Signal Transduction