Effects of MK-801 (dizocilpine) on brain cell membrane function and energy metabolism in experimental Escherichia coli meningitis in the newborn piglet

J Korean Med Sci. 2003 Apr;18(2):236-41. doi: 10.3346/jkms.2003.18.2.236.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blood Glucose / metabolism
  • Brain / cytology
  • Brain / drug effects*
  • Brain / metabolism
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Cerebral Cortex / metabolism
  • Dizocilpine Maleate / pharmacology*
  • Energy Metabolism*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / cerebrospinal fluid
  • Lactic Acid / blood
  • Leukocytes / metabolism
  • Meningitis, Escherichia coli / drug therapy
  • Meningitis, Escherichia coli / metabolism*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology*
  • Random Allocation
  • Swine
  • Tumor Necrosis Factor-alpha / cerebrospinal fluid

Substances

  • Blood Glucose
  • Excitatory Amino Acid Antagonists
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • Lactic Acid
  • Glutamic Acid
  • Dizocilpine Maleate