Antiepileptic drugs and brain maturation: fetal exposure to lamotrigine generates cortical malformations in rats

Autor: Emilio Perucca, Yehezkel Ben-Ari, Isabel Jorquera, Alfonso Represa, Valentina Franco, Jean Bernard Manent
Přispěvatelé: Tyzio, Roman, Epilepsie et ischémie cérébrale, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine and Therapeutics, Università degli Studi di Pavia = University of Pavia (UNIPV), Institute of Neurology (IRCCS), C. Mondino Foundation, University of Pavia
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Levetiracetam
MESH: Hippocampus
Litter Size
medicine.medical_treatment
MESH: Triazines
MESH: Neurons
Cell Count
Weight Gain
MESH: Litter Size
Hippocampus
MESH: Piracetam
MESH: Dose-Response Relationship
Drug
Epilepsy
0302 clinical medicine
MESH: Pregnancy
Cell Movement
Pregnancy
MESH: Malformations of Cortical Development
MESH: Animals
MESH: Cell Movement
Neurons
0303 health sciences
Triazines
Brain
Immunohistochemistry
MESH: Phenobarbital
3. Good health
Malformations of Cortical Development
MESH: Teratogens
Teratogens
Neurology
Phenobarbital
MESH: Weight Gain
Anticonvulsants
Female
medicine.drug
Topiramate
medicine.medical_specialty
MESH: Rats
Fructose
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Lamotrigine
Vigabatrin
03 medical and health sciences
MESH: Brain
MESH: Anticonvulsants
Internal medicine
medicine
Animals
Rats
Wistar
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
030304 developmental biology
Dose-Response Relationship
Drug
business.industry
MESH: Cell Count
MESH: Immunohistochemistry
MESH: Rats
Wistar
medicine.disease
Piracetam
Teratology
Rats
Anticonvulsant
Endocrinology
Neurology (clinical)
business
MESH: Female
MESH: Fructose
030217 neurology & neurosurgery
Zdroj: Epilepsy Research
Epilepsy Research, 2008, 78 (2-3), pp.131-9. ⟨10.1016/j.eplepsyres.2007.10.014⟩
Epilepsy Research, Elsevier, 2008, 78 (2-3), pp.131-9. ⟨10.1016/j.eplepsyres.2007.10.014⟩
ISSN: 0920-1211
1872-6844
DOI: 10.1016/j.eplepsyres.2007.10.014
Popis: International audience; Intake of antiepileptic drugs (AEDs) during pregnancy can provoke severe and subtle fetal malformations associated with deleterious sequelae, reflecting the need for experimental investigations on the comparative teratogenic potential of these agents. We recently reported that prenatal exposure to vigabatrin and valproate, two AEDs which act through GABAergic mechanisms, induces hippocampal and cortical dysplasias in rodents. We have now investigated the effects of phenobarbital (PB, 30 mg/kg day) i.p.), a drug also endowed with GABAergic effects, and the new generation AEDs lamotrigine (LTG, 5-20mg/kg/day i.p.), topiramate (TPM, 10mg/kg/day i.p.), and levetiracetam (LEV, 50mg/kg/day i.p.) on brain development. Prenatal exposure to LTG induced hippocampal and cortical malformations in a dose-dependent manner, at maternal plasma concentrations within the clinically occurring range. These abnormalities were not observed after exposure to PB, TP and LEV. These observations raise concerns about potential clinical correlates and call for detailed comparative investigations on the consequences of AED use during pregnancy.
Databáze: OpenAIRE
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