title: The glutamate AMPA receptor antagonist, YM872, attenuates regional cerebral edema and IgG immunoreactivity following experimental brain injury in rats.
abstract: We previously reported the neuroprotective effects of the glutamate AMPA receptor antagonist YM872 on neurobehavioral motor function and cortical tissue loss (lesion volume) in a brain-injured rat model. Here we examined its effect on brain edema and the breakdown of the blood-brain barrier (BBB). Rats subjected to severe right lateral (parasagittal) fluid-percussion brain injury or sham injury received a 4-hr intravenous infusion of YM872 (20 mg/kg/ hr, 20 mg/3 ml) or normal saline starting at 15 min post-injury. At 48 hr we removed their brains and evaluated the cerebral regional edema by the wet weight/dry weight method. Another group of rats was transcardially fixed with 10% formalin at 2 weeks after injury. Serial brain sections were immunostained for endogenous IgG and the extent and intensity of staining were evaluated. The administration of YM872 resulted in a significant reduction in regional cerebral edema in the injured parietal cortex and a markedly reduced area of IgG immunoreactivy in the injured cortex. Our results indicate that the post-traumatic administration of YM872 may be neuroprotective by reducing BBB breakdown and regional cerebral edema.
authors.affiliation: Department of Emergency and Critical Care Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Atsumi
authors.forename: S
authors.initials: S
authors.lastname: Hoshino
authors.forename: T
authors.initials: T
authors.lastname: Furukawa
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Asakura
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: A
authors.initials: A
authors.lastname: Teramoto
mesh_terms: D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism*; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000378:metabolism*; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors
chemical_list: D007093:Imidazoles; D007074:Immunoglobulin G; D011810:Quinoxalines; D018091:Receptors, AMPA; C110629:YM 872