Screening for the effects of antiepileptic drugs on short term plasticity using a time efficient bioassay.

Ghassan I. Gholmieh, Spiros H. Courellis, Lan S. Chen

Research output: Contribution to journalArticle

Abstract

Screening for changes in the short-term plasticity (STP) characteristics induced by antiepileptic drugs (AEDs) can be accelerated using a novel in vitro bioassay. The bioassay is based on the analysis of varying population spike (PS) amplitudes recorded in the CA1 region of the hippocampal slice in response to Poisson distributed random electrical stimuli. Three antiepileptic drugs (phenytoin 100 microM, carbamazepine 100 microM, and valproate 700 microM) were tested at maximal effective therapeutic concentrations. The data were analyzed using an advanced nonlinear approach that is more specific and time-efficient than the conventional paired pulse and fixed frequency train methods. STP was quantified by the first and the second order Volterra kernels. The first order kernel (k1) represented the mean PS amplitude while the second order kernel (k2) quantified the effect on the current PS amplitude of the interaction between the current stimulus impulse and each past stimulus impulse within a time (memory) window mu. The mean PS (k1 decreased by 15%, 10%, and 7% when phenytoin, carbamazepine, and valproate were added respectively. Phenytoin caused an increase in the k2 peak facilitation in the high frequency domain. Carbamazepine impaired frequency facilitation in the theta frequency range by causing a left shift in the second order kernel.

Original languageEnglish (US)
Pages (from-to)2247-2252
Number of pages6
JournalConference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference
StatePublished - 2007
Externally publishedYes

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Bioassay
Biological Assay
Anticonvulsants
Plasticity
Carbamazepine
Screening
Phenytoin
Valproic Acid
Population
Hippocampal CA1 Region
Data storage equipment
Therapeutics

ASJC Scopus subject areas

  • Computer Vision and Pattern Recognition
  • Signal Processing
  • Biomedical Engineering
  • Health Informatics

Cite this

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title = "Screening for the effects of antiepileptic drugs on short term plasticity using a time efficient bioassay.",
abstract = "Screening for changes in the short-term plasticity (STP) characteristics induced by antiepileptic drugs (AEDs) can be accelerated using a novel in vitro bioassay. The bioassay is based on the analysis of varying population spike (PS) amplitudes recorded in the CA1 region of the hippocampal slice in response to Poisson distributed random electrical stimuli. Three antiepileptic drugs (phenytoin 100 microM, carbamazepine 100 microM, and valproate 700 microM) were tested at maximal effective therapeutic concentrations. The data were analyzed using an advanced nonlinear approach that is more specific and time-efficient than the conventional paired pulse and fixed frequency train methods. STP was quantified by the first and the second order Volterra kernels. The first order kernel (k1) represented the mean PS amplitude while the second order kernel (k2) quantified the effect on the current PS amplitude of the interaction between the current stimulus impulse and each past stimulus impulse within a time (memory) window mu. The mean PS (k1 decreased by 15{\%}, 10{\%}, and 7{\%} when phenytoin, carbamazepine, and valproate were added respectively. Phenytoin caused an increase in the k2 peak facilitation in the high frequency domain. Carbamazepine impaired frequency facilitation in the theta frequency range by causing a left shift in the second order kernel.",
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