title: Edaravone attenuates impairment of synaptic plasticity in granule cell layer of the dentate gyrus following traumatic brain injury.
abstract: Effects of edaravone, a free radical scavenger, on post-traumatic impairment of long-term potentiation (LTP) were examined in granule cell layers of the dentate gyrus (DG) in vitro. Field EPSPs (fEPSPs) evoked by stimulation of the perforant path (PP) were recorded extracellularly in the DG one week after a moderate impact applied by a fluid percussion injury (FPI) device. High frequency stimulation (HFS) of the PP caused LTP of the fEPSP-slope in slices from naïve and sham-operated rats, however, the LTP was strongly depressed in slices from FPI rats. Intraperitoneal administration of edaravone 15 min after FPI prevented the hyperactivities of DG neurons and attenuated impairment of the LTP in FPI rat dentate granular cells. In vitro application of spermine NONOate (sp-NO), a nitric oxide (NO) donor, for 30 min produced a gradual increase in the fEPSP-slope, lasting for more than 2 h. Edaravone attenuated the enhancement of the fEPSP-slope induced by sp-NO. After sp-NO treatment HFS could not produce an obvious LTP in the DG granule cell layer. Pretreatment of DG slices with edaravone prevented the sp-NO-induced impairment of LTP. These results suggest that administration of edaravone after FPI protects against post-traumatic impairment of LTP in granule cell layers of the DG, possibly by scavenging NO-related radicals.
authors.affiliation: Department of Physiology, Kurume University School of Medicine, Kurume University, Kurume 830-0011, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Yamashita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasuo
authors.forename: Takashi
authors.initials: T
authors.lastname: Tokutomi
authors.forename: Minoru
authors.initials: M
authors.lastname: Shigemori
authors.forename: Takashi
authors.initials: T
authors.lastname: Akasu
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D000077553:Edaravone; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D023421:Models, Animal; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
chemical_list: D016166:Free Radical Scavengers; D020030:Nitric Oxide Donors; C091861:spermine nitric oxide complex; D013096:Spermine; D000077553:Edaravone; D000983:Antipyrine