The effect of MK-801 on extracellular neuroactive amino acids in hippocampus after closed head injury followed by hypoxia in rats.
Increased neuronal vulnerability to ischemia or hypoxia has been demonstrated following traumatic brain injury but not explained. Animal data suggest that neuronal damage after traumatic brain injury is caused mainly by massive glutamate release that activates N-methyl-D-aspartate (NMDA) receptors. Using rat models with controlled closed head injury (CHI) followed by hypoxia, we investigated extracellular concentrations of neuroactive amino acids in the hippocampus by in vivo microdialysis. CHI alone produced an immediate increase of glutamate and taurine; hypoxia alone did not alter amino acid concentrations. CHI followed by hypoxia produced a biphasic increase in extracellular glutamate and taurine, with an immediate peak after CHI and a prolonged plateau after hypoxia. Though changes in gamma-aminobutylic acid (GABA) concentration is also prolonged by combined traumatic and hypoxic insults, it showed less alteration than glutamate. Pre-treatment with dizocilpine maleate (MK-801), a non-competitive NMDA antagonist, did not affect the immediate peak of glutamate after CHI but significantly diminished the prolonged plateau after hypoxia. These findings suggest that traumatic brain injury may increase hypoxic release of glutamate, contributing to increased vulnerability to hypoxia. Our data suggest that MK-801 may be beneficial in preventing secondary neuronal damages by hypoxia.
Katoh
H
H
Department of Neurosurgery, National Defense Medical College, Saitama, Japan. yx8h-ktu@asahi-net.or.jp
Sima
K
K
Nawashiro
H
H
Wada
K
K
Chigasaki
H
H
D000596:Amino Acids / Q000187:drug effects*; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D016291:Dizocilpine Maleate