109451
论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
- 3.4 Breast Cancer (Dove Med Press)
- 3.2 Clin Epidemiol
- 2.6 Cancer Manag Res
- 2.9 Infect Drug Resist
- 3.7 Clin Interv Aging
- 5.1 Drug Des Dev Ther
- 3.1 Int J Chronic Obstr
- 6.6 Int J Nanomed
- 2.6 Int J Women's Health
- 2.9 Neuropsych Dis Treat
- 2.8 OncoTargets Ther
- 2.0 Patient Prefer Adher
- 2.2 Ther Clin Risk Manag
- 2.5 J Pain Res
- 3.0 Diabet Metab Synd Ob
- 3.2 Psychol Res Behav Ma
- 3.4 Nat Sci Sleep
- 1.8 Pharmgenomics Pers Med
- 2.0 Risk Manag Healthc Policy
- 4.1 J Inflamm Res
- 2.0 Int J Gen Med
- 3.4 J Hepatocell Carcinoma
- 3.0 J Asthma Allergy
- 2.2 Clin Cosmet Investig Dermatol
- 2.4 J Multidiscip Healthc
已发表论文
佩兰帕奈尔通过激活 FSP1 调节脑缺血后的神经炎症和铁死亡
Authors Lv JM, Pan YJ, Wang X, Zhang MM, Li W, Liu J, Wang T
Received 4 June 2025
Accepted for publication 3 October 2025
Published 17 October 2025 Volume 2025:18 Pages 14423—14437
DOI https://doi.org/10.2147/JIR.S544785
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Prof. Dr. Dharmappa Krishnappa
Jian-Meng Lv, Ya-Juan Pan, Xuan Wang, Mei-Mei Zhang, Wei Li, Juan Liu, Tao Wang
Department of Neurology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, 710068, People’s Republic of China
Correspondence: Tao Wang, Department of Neurology, Shaanxi Provincial People’s Hospital, 256 Youyi West Road, Xi’an, Shaanxi, 710068, People’s Republic of China, Email wangtao_sxrm@163.com
Purpose: Ischemic stroke remains a leading cause of global disability and mortality, with neuroinflammation and ferroptosis emerging as critical contributors to secondary neuronal damage. Perampanel, a non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, exhibits neuroprotective properties in neurological disorders, yet its mechanisms in ischemic stroke remain incompletely understood. This study investigated the therapeutic potential of post-injury perampanel administration in both in vivo and in vitro models, focusing on neuroinflammation, ferroptosis, and the role of ferroptosis suppressor protein 1 (FSP1).
Methods: Rats received intraperitoneal perampanel (1.5 mg/kg) 10– 15 minutes post-reperfusion for 3 days and exposed to middle cerebral artery occlusion (MCAO) for 60 minutes. Neurological function, neuronal survival, and markers of neuroinflammation and ferroptosis were assessed via immunostaining, Western blot, and behavioral tests. The in vitro ischemia model was mimicked by oxygen glucose deprivation (OGD) in primary cultured cortical neurons.
Results: Perampanel significantly attenuated MCAO-induced neuronal loss (NeuN+ cells) and improved motor coordination in rotating pole tests. It suppressed microglial (Iba-1+) and astrocytic (GFAP+) activation, indicating its anti-inflammatory effects. Mechanistically, perampanel reversed the MCAO-driven downregulation of ferroptosis markers FTH-1 and GPX-4, while enhancing neuronal FSP1 expression. Crucially, the FSP1 inhibitor icFSP1 abolished perampanel-mediated neuroprotection, neuronal preservation, and ferroptosis suppression, supporting the FSP1-dependent mechanisms. In in vitro conditions, perampanel exerted protective effects in a dose- and time-dependent manner. The results of immunostaining and Western blot showed that perampanel attenuated neuronal ferroptosis via activation of FSP1.
Conclusion: These findings demonstrate that perampanel mitigates post-ischemic brain injury by inhibiting neuroinflammation and neuronal ferroptosis via FSP1 activation. This study highlights FSP1 as a novel therapeutic target and positions perampanel as a promising candidate for ischemic stroke treatment, leveraging its established safety profile and clinical availability.
Keywords: stroke, neuroinflammation, ferroptosis, FSP1
Department of Neurology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, 710068, People’s Republic of China
Correspondence: Tao Wang, Department of Neurology, Shaanxi Provincial People’s Hospital, 256 Youyi West Road, Xi’an, Shaanxi, 710068, People’s Republic of China, Email wangtao_sxrm@163.com
Purpose: Ischemic stroke remains a leading cause of global disability and mortality, with neuroinflammation and ferroptosis emerging as critical contributors to secondary neuronal damage. Perampanel, a non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, exhibits neuroprotective properties in neurological disorders, yet its mechanisms in ischemic stroke remain incompletely understood. This study investigated the therapeutic potential of post-injury perampanel administration in both in vivo and in vitro models, focusing on neuroinflammation, ferroptosis, and the role of ferroptosis suppressor protein 1 (FSP1).
Methods: Rats received intraperitoneal perampanel (1.5 mg/kg) 10– 15 minutes post-reperfusion for 3 days and exposed to middle cerebral artery occlusion (MCAO) for 60 minutes. Neurological function, neuronal survival, and markers of neuroinflammation and ferroptosis were assessed via immunostaining, Western blot, and behavioral tests. The in vitro ischemia model was mimicked by oxygen glucose deprivation (OGD) in primary cultured cortical neurons.
Results: Perampanel significantly attenuated MCAO-induced neuronal loss (NeuN+ cells) and improved motor coordination in rotating pole tests. It suppressed microglial (Iba-1+) and astrocytic (GFAP+) activation, indicating its anti-inflammatory effects. Mechanistically, perampanel reversed the MCAO-driven downregulation of ferroptosis markers FTH-1 and GPX-4, while enhancing neuronal FSP1 expression. Crucially, the FSP1 inhibitor icFSP1 abolished perampanel-mediated neuroprotection, neuronal preservation, and ferroptosis suppression, supporting the FSP1-dependent mechanisms. In in vitro conditions, perampanel exerted protective effects in a dose- and time-dependent manner. The results of immunostaining and Western blot showed that perampanel attenuated neuronal ferroptosis via activation of FSP1.
Conclusion: These findings demonstrate that perampanel mitigates post-ischemic brain injury by inhibiting neuroinflammation and neuronal ferroptosis via FSP1 activation. This study highlights FSP1 as a novel therapeutic target and positions perampanel as a promising candidate for ischemic stroke treatment, leveraging its established safety profile and clinical availability.
Keywords: stroke, neuroinflammation, ferroptosis, FSP1