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Neurochemical Research

, Volume 43, Issue 4, pp 878–885 | Cite as

Axon Initial Segment Structural Plasticity is Involved in Seizure Susceptibility in a Rat Model of Cortical Dysplasia

  • Zong-Wei Yue
  • Ye-Lan Wang
  • Bo Xiao
  • Li Feng
Original Paper

Abstract

Cortical dysplasia is the most common etiology of intractable epilepsy. Both excitability changes in cortical neurons and neural network reconstitution play a role in cortical dysplasia epileptogenesis. Recent research shows that the axon initial segment, a subcompartment of the neuron important to the shaping of action potentials, adjusts its position in response to changes in input, which contributes to neuronal excitability and local circuit balance. It is unknown whether axon initial segment plasticity occurs in neurons involved in seizure susceptibility in cortical dysplasia. Here, we developed a “Carmustine”- “pilocarpine” rat model of cortical dysplasia and show that it exhibits a lower seizure threshold, as indicated by behavior studies and electroencephalogram monitoring. Using immunofluorescence, we measured the axon initial segment positions of deep L5 somatosensory neurons and show that it is positioned closer to the soma after acute seizure, and that this displacement is sustained in the chronic phase. We then show that Nifedipine has a dose-dependent protective effect against axon initial segment displacement and increased seizure susceptibility. These findings further our understanding of the pathophysiology of seizures in cortical dysplasia and suggests Nifedipine as a potential therapeutic agent.

Keywords

Axon initial segment Cortical dysplasia Nifedipine Seizure susceptibility Structural plasticity 

Notes

Acknowledgements

This work was supported by Grants from the Natural Science Foundation of China (Grant Numbers: 81000553 and 81771407).

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.1Neurology Department, Xiangya HospitalCentral South UniversityChangshaChina

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