Edaravone dexborneol attenuates oxidative stress in experimental subarachnoid hemorrhage via Keap1/Nrf2 signaling pathway

作者：Kunyuan Zhu, Shijun Bi, Zechao Zhu, Wenxu Zhang, Xinyu Yang, Jiashuo Li, Guobiao Liang, Chunyong Yu, Pengyu Pan · 发表于：Frontiers in Pharmacology · 年份：2024 · DOI：10.3389/fphar.2024.1342226 · 被引用次数：8 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Intracranial Aneurysms: Treatment and Complications、Traumatic Brain Injury and Neurovascular Disturbances

Background: Subarachnoid hemorrhage (SAH) serves as a disease characterized by high incidence rate, which is exceedingly prevalent and severe. Presently, there is no unambiguous or efficacious intervention for the neurological impairment following SAH. Administering multi-targeted neuroprotective agents to reduce oxidative stress (OS) and neuroinflammation caused by early brain injury (EBI) has been demonstrated to improve neurological function and prognosis following SAH. Edaravone dexborneol (EDB), a novel multi targeted neuroprotective medication, combines four parts edaravone (EDA) with 1 part (+)-borneol in proportion. Clinical trials conducted in China have revealed during 2 days of acute ischemic stroke (AIS), early administration of EDB leads to improved therapeutic outcomes compared to treatment in EDA monotherapy. Currently, there is no clear evidence that EDB can effectively treat SAH, therefore, our study aims to investigate its potential therapeutic effects and mechanisms on EBI after SAH. Method: We used the intravascular threading method to establish a mouse model of SAH to explore whether EDA and EDB could produce anti-OS and anti-apoptosis effects. Behavioral assessment of mice was conducted using the balance beam experiment and the modified Garcia scoring system. Neuronal damage due to OS and Keap1/Nrf2 signaling pathway were detected through techniques of immunofluorescence, Western blotting, spectrophotometry. The group of EDA and EDB were injected intrape...