Effects of MK-801 (dizocilpine) on brain cell membrane function and energy metabolism in experimental Escherichia coli meningitis in the newborn piglet.
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.
Ko
Sun Young
SY
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Shim
Jae Won
JW
Kim
Sung Shin
SS
Kim
Mi Jung
MJ
Chang
Yun Sil
YS
Park
Won Soon
WS
Shin
Son Moon
SM
Lee
Mun Hyang
MH
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
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