title: Short-term use of antiepileptic drugs is neurotoxic to the immature brain.
abstract: Previous studies have shown that the long-term use of antiepileptic drugs can cause nervous system damage. However, short-term antiepileptic drug treatment is frequently given to infants, especially neonates, to control seizure. Whether the short-term use of antiepileptic drugs is neurotoxic remains unclear. In the present study, immature rats, 3-21 days of age, were intraperitoneally injected with phenobarbital and/or topiramate for 3 consecutive days. Hematoxylin-eosin and immunohistochemical staining revealed that phenobarbital and topiramate, individually or in combination, were cytotoxic to hippocampal CA1 neurons and inhibited the expression of GluR1 and NR2B, excitatory glutamate receptor subunits. Furthermore, the combination of the two drugs caused greater damage than either drug alone. The results demonstrate that the short-term use of antiepileptic drugs damages neurons in the immature brain and that the combined use of antiepileptic drugs exacerbates damage. Our findings suggest that clinicians should consider the potential neurotoxic risk associated with the combined use of antiepileptic drugs in the treatment of seizure.
authors.affiliation: Department of Pediatrics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Xue-Ying
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pediatrics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Shao-Ping
authors.initials: SP
authors.lastname: Huang
keywords: NSFC grant; antiepileptic drugs; glutamate receptor; hippocampus; immature brain; nerve regeneration; neural regeneration; seizure; synaptic plasticity