The glutamate AMPA receptor antagonist, YM872, attenuates cortical tissue loss, regional cerebral edema, and neurological motor deficits after experimental brain injury in rats.
A massive increase in extracellular glutamate is thought to contribute to brain damage after traumatic brain injury. We examined the neuroprotective effect of the AMPA receptor antagonist YM872 in a rat head injury model using the fluid-percussion procedure. Male Sprague-Dawley rats were subjected to right lateral (parasagittal) fluid-percussion brain injury or sham injury. At 15 min postinjury, they received either YM872 (20 mg/kg/h, 20 mg/3 mL) or normal saline (vehicle) intravenously for 4 h. The administration of YM872 significantly improved the composite neuroscore at 1 and 2 weeks postinjury (p < 0.05), and markedly reduced the volume of tissue loss in the injured cortex (p < 0.05). It also significantly reduced cerebral edema in the ipsilateral parietal cortex at 48 h postinjury (p < 0.01). These results indicate that the posttraumatic administration of YM872 may be neuroprotective by ameliorating cortical tissue loss and regional cerebral edema, and suggest the importance of AMPA receptors in traumatic brain damage involving secondary injury processes.
Furukawa
Tetsuya
T
Department of Neurosurgery, Nippon Medical School, Tokyo, Japan.
Hoshino
Shigeru
S
Kobayashi
Shiro
S
Asakura
Takayuki
T
Takahashi
Masayasu
M
Atsumi
Takahiro
T
Teramoto
Akira
A
D000818:Animals; D001831:Body Temperature; D001929:Brain Edema / Q000188:drug therapy; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology*; D018698:Glutamic Acid / Q000378:metabolism; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011810:Quinoxalines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists; D020127:Recovery of Function / Q000187:drug effects
D007093:Imidazoles; D018696:Neuroprotective Agents; D011810:Quinoxalines; D018091:Receptors, AMPA; C110629:YM 872; D018698:Glutamic Acid