The glutamate AMPA receptor antagonist, YM872, attenuates regional cerebral edema and IgG immunoreactivity following experimental brain injury in rats.
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.
Atsumi
T
T
Department of Emergency and Critical Care Medicine, Nippon Medical School, Tokyo, Japan.
Hoshino
S
S
Furukawa
T
T
Kobayashi
S
S
Asakura
T
T
Takahashi
M
M
Yamamoto
Y
Y
Teramoto
A
A
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
D007093:Imidazoles; D007074:Immunoglobulin G; D011810:Quinoxalines; D018091:Receptors, AMPA; C110629:YM 872