title: Effects of MK-801 (dizocilpine) on brain cell membrane function and energy metabolism in experimental Escherichia coli meningitis in the newborn piglet.
abstract: We evaluated the efficacy of non-competitive N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine) as an adjuvant therapy in experimental neonal bacterial meningitis. Meningitis was induced by injecting 10(6) colony forming units of Escherichia coli into the cisterna magna. MK-801 3 mg/kg was given as a bolus intravenous injection, 30 min before the induction of meningitis. MK-801 did not down-modulate the inflammatory parameters, such as increased intracranial pressure, cerebrospinal fluid (CSF) leukocytosis, increased lactate and TNF-alpha levels in the CSF, and hypoglycorrhachia observed in the meningitis group. MK-801 did not significantly attenuate the elevated glutamate concentration in the CSF. However, MK-801 showed some neuroprotective effects as evidenced by significant attenuation of cerebral lipid peroxidation products (conjugated dienes) and increase of brain high-energy phosphate compounds (ATP and PCr). Improvement in cerebral cortical cell membrane Na+, K+ -ATPase activity did not reach a statistical significance. These results suggest that MK-801 was effective in ameliorating brain injury in neonatal bacterial meningitis, although it failed to attenuate the inflammatory responses.
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Ko
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Shim
authors.forename: Sung Shin
authors.initials: SS
authors.lastname: Kim
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Yun Sil
authors.initials: YS
authors.lastname: Chang
authors.forename: Won Soon
authors.initials: WS
authors.lastname: Park
authors.forename: Son Moon
authors.initials: SM
authors.lastname: Shin
authors.forename: Mun Hyang
authors.initials: MH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004734:Energy Metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000134:cerebrospinal fluid; D019344:Lactic Acid / Q000097:blood; D007962:Leukocytes / Q000378:metabolism; D020814:Meningitis, Escherichia coli / Q000188:drug therapy / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
chemical_list: D001786:Blood Glucose; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D018698:Glutamic Acid; D016291:Dizocilpine Maleate