Antiepileptic drugs and the developing brain |
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| Authors: | A M Kaindl S Asimiadou D Manthey M vd Hagen L Turski C Ikonomidou |
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| Institution: | (1) Department of Pediatric Neurology, Charité, University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany;(2) Department of Pediatric Neurology, Children’s Hospital, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden, Germany;(3) Solvay Pharmaceuticals Research Laboratories, C. J. van Houtenlaan 36, 1392 CP Weesp, The Netherlands |
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| Abstract: | Epilepsy is the most common neurological disorder in young humans. Antiepileptic drugs (AEDs) which are used to treat seizures
in infants, children and pregnant women can cause cognitive impairment, microcephaly and birth defects. Ion channels, neurotransmitters
and second messenger systems constitute molecular targets of AEDs. The same targets regulate brain processes essential both
for propagation of seizures and for learning, memory and emotional behavior. Thus, AEDs can influence brain function and brain
development in undesired ways. Here we review mechanisms of action of AEDs, examine clinical evidence for their adverse effects
in the developing human brain, and present studies on cognitive and behavioral effects in animal models. Furthermore, we discuss
mechanisms responsible for adverse effects of AEDs in the developing mammalian brain, including interference with cell proliferation
and migration, axonal arborization, synaptogenesis, synaptic plasticity and physiological apoptotic cell death.
Received 3 August 2005; received after revision 13 October 2005; accepted 1 November 2005 |
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| Keywords: | Antiepileptic drugs development apoptosis neurodegeneration synaptogenesis |
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