Abstract:
:Epilepsy is the most common neurological disorder of young humans. Each year 150,000 children in the United States experience their first seizure. Antiepileptic drugs (AEDs), used to treat seizures in children, infants, and pregnant women, cause cognitive impairment, microcephaly, and birth defects. The cause of unwanted effects of therapy with AEDs is unknown. Here we reveal that phenytoin, phenobarbital, diazepam, clonazepam, vigabatrin, and valproate cause apoptotic neurodegeneration in the developing rat brain at plasma concentrations relevant for seizure control in humans. Neuronal death is associated with reduced expression of neurotrophins and decreased concentrations of survival-promoting proteins in the brain. beta-Estradiol, which stimulates pathways that are activated by neurotrophins, ameliorates AED-induced apoptotic neurodegeneration. Our findings present one possible mechanism to explain cognitive impairment and reduced brain mass associated with prenatal or postnatal exposure of humans to antiepileptic therapy.
journal_name
Proc Natl Acad Sci U S Aauthors
Bittigau P,Sifringer M,Genz K,Reith E,Pospischil D,Govindarajalu S,Dzietko M,Pesditschek S,Mai I,Dikranian K,Olney JW,Ikonomidou Cdoi
10.1073/pnas.222550499keywords:
subject
Has Abstractpub_date
2002-11-12 00:00:00pages
15089-94issue
23eissn
0027-8424issn
1091-6490pii
222550499journal_volume
99pub_type
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