Citation

Zhou Y, Tian M, Wang HD, Gao CC, Zhu L, Lin YX, Fang J, Ding K. Int. J. Neurosci. 2019; 129(8): 801-807.

Affiliation

a Department of Neurosurgery, Jinling Hospital, Jinling School of Clinical Medicine , Nanjing Medical University , Jiangsu , Nanjing 210002 , China.

Copyright

(Copyright © 2019, Informa - Taylor and Francis Group)

DOI

10.1080/00207454.2019.1569652

PMID

30648894

Abstract

Background Treatment of blast-induced traumatic brain injury (bTBI) has been hindered. Previous studies have demonstrated that oxidative stress may contribute to the pathophysiological process. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway exhibits a protective effect after traumatic brain injury (TBI). This study explored whether the Nrf2-ARE pathway was activated in a modified bTBI mouse model.

METHOD Mice were randomly divided into six groups: the 6 h, 1 d, 3 d, 7 d, and 14 d after bTBI groups and a sham group. The protein levels of nuclear Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase-1 (NQO1) were detected using western blot, and HO-1 and NQO1 mRNA levels were determined by real-time quantitative polymerase chain reaction. Moreover, HO-1 and Nrf2 were localized using histological staining.

RESULTS The protein level of the Nrf2-ARE pathway in the frontal lobe increased significantly in the 3 d after bTBI. The HO-1 and NQO1 mRNA levels also reached a peak in the frontal lobe 3 d after bTBI. The histological staining demonstrated higher expression of HO-1 in the frontal lobe and hippocampus 3 d after bTBI, when nuclear import of Nrf2 reached a peak in the frontal lobe.

CONCLUSIONS bTBI activated the Nrf2-ARE signaling pathway in the brain. The peak activation time in the frontal lobe may be 3 d after injury, and activating the Nrf2 pathway could be a new direction for treatment.

Language: en

Keywords

Blast induced traumatic brain injury; NAD(P)H: quinone oxidoreductase-1; Nuclear factor erythroid 2-related factor 2; heme oxygenase-1; shock tube