title: Effect of noncompetitive blockade of N-methyl-D-aspartate receptors on the neurochemical sequelae of experimental brain injury.
abstract: Pharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global and focal ischemia and hypoglycemia, and improves neurological outcome after experimental spinal cord injury. The present study examined the effects of the noncompetitive N-methyl-D-aspartate receptor blocker MK-801 on neurochemical sequelae following experimental fluid-percussion brain injury in the rat. Fifteen minutes after fluid-percussion brain injury (2.8 atmospheres), animals received either MK-801 (1 mg/kg, i.v.) or saline. MK-801 treatment significantly attenuated the development of focal brain edema at the site of injury 48 h after brain injury, significantly reduced the increase in tissue sodium, and prevented the localized decline in total tissue magnesium that was observed in injured tissue of saline-treated animals. Using phosphorus nuclear magnetic resonance spectroscopy, we also observed that MK-801 treatment improved brain metabolic status and promoted a significant recovery of intracellular free magnesium concentrations that fell precipitously after brain injury. These results suggest that excitatory amino acid neurotransmitters may be involved in the pathophysiological sequelae of traumatic brain injury and that noncompetitive N-methyl-D-aspartate receptor antagonists may effectively attenuate some of the potentially deleterious neurochemical sequelae of brain injury.
authors.affiliation: Department of Surgery, University of Connecticut Health Center, Farmington 06032.
authors.forename: T K
authors.initials: TK
authors.lastname: McIntosh
authors.forename: R
authors.initials: R
authors.lastname: Vink
authors.forename: H
authors.initials: H
authors.lastname: Soares
authors.forename: R
authors.initials: R
authors.lastname: Hayes
authors.forename: R
authors.initials: R
authors.lastname: Simon
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001929:Brain Edema / Q000378:metabolism; D001930:Brain Injuries / Q000097:blood / Q000378:metabolism*; D002245:Carbon Dioxide / Q000097:blood; D002412:Cations; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010100:Oxygen / Q000097:blood; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values
chemical_list: D000927:Anticonvulsants; D002412:Cations; D003986:Dibenzocycloheptenes; D010710:Phosphates; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D010725:Phosphocreatine; D002245:Carbon Dioxide; D016291:Dizocilpine Maleate; D000255:Adenosine Triphosphate; D010100:Oxygen