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) β-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.
Bibliographical noteFunding Information:
We thank Drs. Sangduk Kim (Korea University) and Won Ki Kim (Ewha Womans University) for valuable comments on the manuscript. This work was supported by a grant from the Korean Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (02-PJ1-PG1-CH06-0001). A part of this work was supported technically by a core facility service of the 21C Frontier Brain Research Center.
- Cerebral ischemia
- Oxygen-glucose deprivation
ASJC Scopus subject areas
- Developmental Neuroscience