Docosahexaenoic Acid Protects Traumatic Brain Injury by Regulating NOX2 Generation via Nrf2 Signaling Pathway

Wei Zhu,Hongguang Chen,Yuexia Ding,Guangqiang Cui,Jian Zhu,Tuo Li,Li Zhao

doi:10.1007/s11064-020-03078-z

Wei Zhu, Hongguang Chen + Show 5 more

Open Access

https://doi.org/10.1007/s11064-020-03078-z

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Journal: Neurochemical research	Publication Date: Jul 16, 2020
Citations: 13	License type: open-access

Affiliation: Yuhuangding Hospital, Qingdao University

Abstract

Docosahexaenoic acid (DHA) is verified to have neuroprotective effects on traumatic brain injury (TBI) rats by activating Nrf2 signaling pathway, but the role of NOX2 in this effect has not been illuminated. So this study explored the role of NOX2 in TBI models treated with DHA, aiming to complete the mechanism of DHA. TBI rat models were constructed with or without DHA treatment, and H2O2-induced hippocampal neurons were pretreated with DHA alone or in combination with Nrf2 inhibitor brusatol. The neurological function, cognitive ability, and cerebral edema degree of rats were assessed. The apoptosis rate and viability of cells was measured. The generation of NOX2, Nrf2, HO-1 and NQO-1 expression levels, and ROS content in hippocampal CA1 region and hippocampal neurons were detected. DHA could not only improve the neurological function, brain edema and cognitive ability in TBI rats, but also decrease effectively the contents of NOX2 and ROS in hippocampal CA1 region and hippocampal neurons. DHA promoted the nuclear transposition of Nrf2 and the expression levels of HO-1 and NQO-1 in hippocampal CA1 region and hippocampal neurons. On the contrary, Nrf2 inhibitor brusatol inhibited the nuclear transposition of Nrf2 and the expression levels of HO-1 and NQO-1 in hippocampal neurons, promoted the generation of ROS and NOX2, and accelerated cell apoptosis. Both in vivo and in vitro experiments demonstrated that DHA treated TBI by reducing NOX2 generation that might function on Nrf2 signaling pathway, providing a potential evidence for its clinical application.

Highlights

Traumatic brain injury (TBI) is one of the common critical cases in neurosurgery, which is one of the main causes of death and disability of young people all over the world [1]
We evaluated the neurological function of the rats and found that the Neurological Severity Score (NSS) score of the rats in traumatic brain injury (TBI) group was sharply elevated in comparison with sham group, whereas the neurological function damage caused by TBI could be reversed after 1 day of Docosahexaenoic acid (DHA) treatment (P < 0.01, Fig. 1a)
Secondary injury after TBI is the main factor affecting the neurological function of patients, so intervention in the treatment window period is beneficial to improve the prognosis of patients and their long-term quality of life [3]

Summary

Introduction

Traumatic brain injury (TBI) is one of the common critical cases in neurosurgery, which is one of the main causes of death and disability of young people all over the world [1]. The mechanism of TBI includes primary injury and secondary injury, primary injury mainly refers to the damage of neurons, glial cells and blood vessels caused by the mechanical force at the moment of craniocerebral injury [2]. Secondary injury refers to the inflammatory response, microglia activation, and oxidative stress occurring after primary injury, which is the main mechanism of chronic neuronal degeneration and neurological dysfunction after craniocerebral injury [3]. In the course of pathology, oxidative stress is considered as the core link of secondary injury [4].

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