Abstract
Perinatal hypoxia-ischemia is one of the most common risk factors for neonatal mortality and permanent neurodevelopmental disability. Topiramate [2,3:4,5-bis-o-(1-methylethylidene) beta-D-fructo-pyranose sulfamate; TPM] is widely used as an antiepileptic agent with multiple targets. In the present study, we found that treatment with TPM reduced the neuronal damage induced by oxygen-glucose deprivation in vitro with strong inhibition of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor. Because perinatal hypoxia is mediated, at least in part, by aberrant glutamatergic excitation, we tested whether treatment with TPM was effective against perinatal brain hypoxia-ischemia. Intraperitoneal or oral pretreatment with TPM was found to reduce the brain damage and subsequent cognitive impairments induced by transient hypoxia-ischemia in perinatal rats. A potent neuroprotective effect of TPM was also observed in a post-treatment regime although post-treatment window appears to be relatively narrow (<2 h). These results suggest that TPM treatment may be beneficial for perinatal hypoxia-ischemia and related damage.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
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Administration, Oral
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Animals
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Animals, Newborn
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Behavior, Animal / drug effects
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Cell Hypoxia
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Cell Survival / drug effects
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Cells, Cultured
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Dose-Response Relationship, Drug
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Fructose / administration & dosage
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Fructose / analogs & derivatives*
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Fructose / pharmacology
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Hypoxia-Ischemia, Brain / pathology
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Hypoxia-Ischemia, Brain / physiopathology
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Hypoxia-Ischemia, Brain / prevention & control*
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Injections, Intraperitoneal
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Maze Learning / drug effects
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N-Methylaspartate / pharmacology
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Neurons / cytology
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Neurons / drug effects
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Neuroprotective Agents / administration & dosage
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Neuroprotective Agents / pharmacology*
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Rats
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Rats, Sprague-Dawley
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Receptors, AMPA / agonists
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Receptors, AMPA / antagonists & inhibitors
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Receptors, AMPA / physiology
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Topiramate
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Substances
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Neuroprotective Agents
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Receptors, AMPA
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Topiramate
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Fructose
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N-Methylaspartate
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6-Cyano-7-nitroquinoxaline-2,3-dione
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid