J Korean Med Sci.  2003 Apr;18(2):236-241. 10.3346/jkms.2003.18.2.236.

Effects of MK-801 (dizocilpine) on Brain Cell Membrane Function and Energy Metabolism in Experimental Escherichia coli Meningitis in the Newborn Piglet

• Ko SY
• Shim JW
• Kim SS
• Kim MJ
• Chang YS
• Park WS
• Shin SM
• Lee MH

• KMID: 2157628
• DOI: http://doi.org/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.

Keyword

Meningitis, Bacterial; Excitatory Amino Acid Antagonists; Energy Metabolism; Brain; Animals, Newborn

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/cerebrospinal fluid