Rosiglitazone inhibits acyl‐CoA synthetase long‐chain family number 4 and improves secondary brain injury in a rat model of surgical brain injury

Author:

Shen Jinchao1,Qian Min1,Wu Muyao2,Tang Jiafeng2,Gong Yating2,Li Jie3,Ji Jinfen1,Dang Baoqi2

Affiliation:

1. Departments of Anesthesiology Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine Jiangsu Province China

2. Departments of Rehabilitation Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine Jiangsu Province China

3. Departments of Intensive Care Unit Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, No.77 Changan Southern Road Jiangsu Province China

Abstract

AbstractFerroptosis is a recently discovered non‐apoptotic form of cellular death. Acyl‐CoA synthetase long‐chain family number 4 (ACSL4) is necessary for iron‐dependent cellular death, and reactive oxygen species (ROS) produced by ACSL4 are the executioners of ferroptosis. Rosiglitazone improves ferroptosis by inhibiting ACSL4. There is no research indicating whether ACSL4 plays a role in cell death after surgical brain injury (SBI). This study aimed to investigate the role of ACSL4 in SBI via the ferroptosis pathway. Ninety male Sprague–Dawley rats were examined using a model of SBI. Subsequently, the inhibitory effect of rosiglitazone on ACSL4 was assessed via western blot, real‐time polymerase chain reaction (PCR), immunofluorescence, fluoro‐jade C staining, Perl's staining, ROS assay, and neurological scoring. The results showed that compared with the Sham group, the protein levels of ACSL4 and transferrin were significantly increased after SBI. Administration of rosiglitazone significantly reduced neuronal necrosis, iron deposition, brain water content and ROS in brain tissue and ameliorated neurological deficits at 48 h after SBI, which was concomitant with decreased transferrin expression. These findings demonstrate that SBI‐induced upregulation of ACSL4 may be partly mediated by the ferroptosis pathway, which can be reversed by rosiglitazone administration.

Publisher

Wiley

Subject

Physiology (medical),Pharmacology,Physiology

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