The Effects of Gabapentin on Epileptic Seizures: A Computational Model

Authors

  • Anand Ramabadran Delbarton School
  • Vidya Desai Pinnacle High School
  • William Longtin
  • Laya Palutla
  • Marianne Bezaire

DOI:

https://doi.org/10.47611/jsr.v11i4.1791

Keywords:

gabapentin, epilepsy, seizure, anticonvulsant, hippocampus, voltage-gated calcium channels, cortical neurons, NMDA receptors, O-LM interneurons, pyramidal cells, basket cells, synaptic transmission, post-synaptic terminal, pre-synaptic terminal, dendritic inhibition, Local Field Potential, Raster plot, Power Spectrum Density

Abstract

Anticonvulsant sedatives are commonly used to stop epileptic seizures; however, many result in significant harmful side-effects. In this paper, we explore gabapentin, an alternative anticonvulsant, as a safer, more effective treatment for epileptic seizures. The goal of our study was to determine the conditions under which gabapentin has the greatest potential to suppress epileptic seizures through its interactions with voltage-gated Ca2+ channels. First, we ran an existing network model of the CA3 region of the hippocampus. Next, we rendered the model seizure prone through impaired dendritic inhibition to pyramidal cells due to the dysfunction of O-LM interneurons. Then, we implemented gabapentin into the network as a parameter that acts as a proxy for dosage and scales the Ca2+ channel conductance in excitatory neurons. By increasing the dosage of gabapentin, the resulting Ca2+ current was decreased, inhibiting the seizure. In fact, at high doses of gabapentin, we saw seizures were significantly suppressed. Our model supports the efficacy of gabapentin as a seizure medication. However, clinical trials are needed to find appropriate dosages and side effects of the drug.

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References or Bibliography

Centers for Disease Control and Prevention. (2020, September 30). Epilepsy data and statistics. Centers for Disease Control and Prevention. https://www.cdc.gov/epilepsy/data/index.html

Fernández-Quintero, Monica L., El Ghaleb, Yousra., Tuluc, Petronel., Campiglio, Marta., Liedl, Klaus R., Flucher , Bernhard E. (2021). Structural determinants of voltage-gating properties in calcium channels, eLife 10:e64087. https://doi.org/10.7554/eLife.64087

Rajakulendran, S., and Hanna, Michael G. (2016). The Role of Calcium Channels in Epilepsy, Cold Spring Harb Perspect Med. 2016 Jan 4;6(1):a022723. https://doi.org/10.1101/cshperspect.a022723

Sanjay, M., Neymotin, S. A., & Krothapalli, S. B. (2015). Impaired dendritic inhibition leads to epileptic activity in a computer model of CA3. Hippocampus, 25(11), 1336–1350. https://senselab.med.yale.edu/ModelDB/ShowModel?model=186768#tabs-1

Published

03-09-2023

How to Cite

Ramabadran, A., Desai, V., Longtin, W., Palutla, L., & Bezaire, M. (2023). The Effects of Gabapentin on Epileptic Seizures: A Computational Model. Journal of Student Research, 11(4). https://doi.org/10.47611/jsr.v11i4.1791

Issue

Section

Research Projects