title: The AMPAR Antagonist Perampanel Attenuates Traumatic Brain Injury Through Anti-Oxidative and Anti-Inflammatory Activity.
abstract: Perampanel is a novel α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) antagonist, approved in over 35 countries as an adjunctive therapy for the treatment of seizures. Recently, it was found to exert protective effects against ischemic neuronal injury in vitro. In the present study, we investigated the potential protective effects of perampanel in a traumatic brain injury (TBI) model in rats. Oral administration with perampanel at a dose of 5 mg/kg exerted no major organ-related toxicities. We found that perampanel significantly attenuated TBI-induced brain edema, brain contusion volume, and gross motor dysfunction. The results of Morris water maze test demonstrated that perampanel treatment also improved cognitive function after TBI. These neuroprotective effects were accompanied by reduced neuronal apoptosis, as evidenced by decreased TUNEL-positive cells in brain sections. Moreover, perampanel markedly inhibited lipid peroxidation and obviously preserved the endogenous antioxidant system after TBI. In addition, enzyme-linked immunosorbent assay (ELISA) was performed at 4 and 24 h after TBI to evaluate the expression of inflammatory cytokines. The results showed that perampanel suppressed the expression of pro-inflammatory cytokines TNF-α and IL-1β, whereas increased the levels of anti-inflammatory cytokines IL-10 and TGF-β1. These data show that the orally active AMPAR antagonist perampanel affords protection against TBI-induced neuronal damage and neurological dysfunction through anti-oxidative and anti-inflammatory activity.
authors.affiliation: Department of Neurosurgery, The 123th Hospital of PLA, Bengbu, 233010, Anhui, China.|Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Dai
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, China.
authors.forename: Zhi-Quan
authors.initials: ZQ
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Luo
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fei
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China. guisb_tiantan@126.com.
authors.forename: Song-Bai
authors.initials: SB
authors.lastname: Gui
authors.affiliation: Department of Neurosurgery, The 123th Hospital of PLA, Bengbu, 233010, Anhui, China. qiyl_PLA123@126.com.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Qi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009570:Nitriles; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018836:Inflammation Mediators; D009570:Nitriles; D011728:Pyridones; D018091:Receptors, AMPA; C551441:perampanel
keywords: AMPA receptor; Inflammation; Oxidative stress; Perampanel; TBI