2. Academic Validation
  3. Edaravone Alleviates Traumatic Brain Injury by Inhibition of Ferroptosis via FSP1 Pathway

Edaravone Alleviates Traumatic Brain Injury by Inhibition of Ferroptosis via FSP1 Pathway

  • Mol Neurobiol. 2024 May 11. doi: 10.1007/s12035-024-04216-2.
Haoyu Shi # 1,  Libiao Song # 1,  Yonghui Wu # 2,  Ruonan Shen 1,  Chenxu Zhang 1,  Xingzhi Liao 3,  Qiuhong Wang 4,  Jie Zhu 5
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Wuxi Clinical College of Anhui Medical University (The 904th Hospital of PLA)/Fifth Clinical Medical College of Anhui Medical University, Wuxi, 214044, Jiangsu Province, China.
  • 2 Department of Neurosurgery, The Second People's Hospital of Lu'an, Lu'an, 237000, Anhui Province, China.
  • 3 Department of Anaesthesiology, Wuxi Clinical College of Anhui Medical University (The 904th Hospital of PLA)/Fifth Clinical Medical College of Anhui Medical University, Wuxi, 214044, Jiangsu Province, China.
  • 4 Department of Ophthalmology, Wuxi Second Hospital Affiliated to Jiangnan University, Wuxi, 214002, Jiangsu Province, China.
  • 5 Department of Neurosurgery, Wuxi Clinical College of Anhui Medical University (The 904th Hospital of PLA)/Fifth Clinical Medical College of Anhui Medical University, Wuxi, 214044, Jiangsu Province, China. zhujie101@126.com.
  • # Contributed equally.
PMID: 38733490 DOI: 10.1007/s12035-024-04216-2
Abstract

Traumatic brain injury (TBI) is a highly severe form of trauma with complex series of reactions in brain tissue which ultimately results in neuronal damage. Previous studies proved that neuronal Ferroptosis, which was induced by intracranial haemorrhage and other reasons, was one of the most primary causes of neuronal damage following TBI. However, the association between neuronal mechanical injury and Ferroptosis in TBI and relevant treatments remain unclear. In the present study, we first demonstrated the occurrence of neuronal Ferroptosis in the early stage of TBI and preliminarily elucidated that edaravone (EDA), a cerebroprotective agent that eliminates oxygen radicals, was able to inhibit Ferroptosis induced by TBI. A cell scratching model was established in PC12 cells, and it was confirmed that mechanical injury induced Ferroptosis in neurons at the early stage of TBI. Ferroptosis suppressor protein 1 (FSP1) plays a significant role in inhibiting Ferroptosis, and we found that iFSP, a Ferroptosis agonist which is capable to inhibit FSP1 pathway, attenuated the anti-ferroptosis effect of EDA. In conclusion, our results suggested that EDA inhibited neuronal Ferroptosis induced by mechanical injury in the early phase of TBI by activating FSP1 pathway, which could provide evidence for future research on prevention and treatment of TBI.

Keywords

Edaravone; Ferroptosis; Ferroptosis suppressor protein 1; Mechanical injury; Traumatic brain injury.

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Products
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  • HY-136057
    99.89%, FSP1 Inhibitor