Nodule excitability in an animal model of periventricular nodular heterotopia

C-fos activation in organotypic hippocampal slices

Emily T. Doisy, H. Jürgen Wenzel, Yi Mu, Danh V. Nguyen, Philip A Schwartzkroin

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Summary Objective Aberrations in brain development may lead to dysplastic structures such as periventricular nodules. Although these abnormal collections of neurons are often associated with difficult-to-control seizure activity, there is little consensus regarding the epileptogenicity of the nodules themselves. Because one common treatment option is surgical resection of suspected epileptic nodules, it is important to determine whether these structures in fact give rise, or essentially contribute, to epileptic activities. Methods To study the excitability of aberrant nodules, we have examined c-fos activation in organotypic hippocampal slice cultures generated from an animal model of periventricular nodular heterotopia created by treating pregnant rats with methylazoxymethanol acetate. Using this preparation, we have also attempted to assess tissue excitability when the nodule is surgically removed from the culture. We then compared c-fos activation in this in vitro preparation to c-fos activation generated in an intact rat treated with kainic acid. Results Quantitative analysis of c-fos activation failed to show enhanced nodule excitability compared to neocortex or CA1 hippocampus. However, when we compared cultures with and without a nodule, presence of a nodule did affect the excitability of CA1 and cortex, at least as reflected in c-fos labeling. Surgical removal of the nodule did not result in a consistent decrease in excitability as reflected in the c-fos biomarker. Significance Our results from the organotypic culture were generally consistent with our observations on excitability in the intact rat - as seen not only with c-fos but also in previous electrophysiologic studies. At least in this model, the nodule does not appear to be responsible for enhanced excitability (or, presumably, seizure initiation). Excitability is different in tissue that contains a nodule, suggesting altered network function, perhaps reflecting the abnormal developmental pattern that gave rise to the nodule.

Original languageEnglish (US)
Pages (from-to)626-635
Number of pages10
JournalEpilepsia
Volume56
Issue number4
DOIs
StatePublished - Apr 1 2015

Fingerprint

Periventricular Nodular Heterotopia
Animal Models
Methylazoxymethanol Acetate
Seizures
Kainic Acid
Neocortex
Hippocampus
Biomarkers
Neurons
Brain

Keywords

  • c-fos
  • Dysplasia
  • Epileptogenicity
  • Nodular heterotopia
  • Organotypic slice cultures
  • Seizure initiation

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Nodule excitability in an animal model of periventricular nodular heterotopia : C-fos activation in organotypic hippocampal slices. / Doisy, Emily T.; Wenzel, H. Jürgen; Mu, Yi; Nguyen, Danh V.; Schwartzkroin, Philip A.

In: Epilepsia, Vol. 56, No. 4, 01.04.2015, p. 626-635.

Research output: Contribution to journalArticle

Doisy, Emily T. ; Wenzel, H. Jürgen ; Mu, Yi ; Nguyen, Danh V. ; Schwartzkroin, Philip A. / Nodule excitability in an animal model of periventricular nodular heterotopia : C-fos activation in organotypic hippocampal slices. In: Epilepsia. 2015 ; Vol. 56, No. 4. pp. 626-635.
@article{2b35d58afb864f43b4de352c17ecf4cc,
title = "Nodule excitability in an animal model of periventricular nodular heterotopia: C-fos activation in organotypic hippocampal slices",
abstract = "Summary Objective Aberrations in brain development may lead to dysplastic structures such as periventricular nodules. Although these abnormal collections of neurons are often associated with difficult-to-control seizure activity, there is little consensus regarding the epileptogenicity of the nodules themselves. Because one common treatment option is surgical resection of suspected epileptic nodules, it is important to determine whether these structures in fact give rise, or essentially contribute, to epileptic activities. Methods To study the excitability of aberrant nodules, we have examined c-fos activation in organotypic hippocampal slice cultures generated from an animal model of periventricular nodular heterotopia created by treating pregnant rats with methylazoxymethanol acetate. Using this preparation, we have also attempted to assess tissue excitability when the nodule is surgically removed from the culture. We then compared c-fos activation in this in vitro preparation to c-fos activation generated in an intact rat treated with kainic acid. Results Quantitative analysis of c-fos activation failed to show enhanced nodule excitability compared to neocortex or CA1 hippocampus. However, when we compared cultures with and without a nodule, presence of a nodule did affect the excitability of CA1 and cortex, at least as reflected in c-fos labeling. Surgical removal of the nodule did not result in a consistent decrease in excitability as reflected in the c-fos biomarker. Significance Our results from the organotypic culture were generally consistent with our observations on excitability in the intact rat - as seen not only with c-fos but also in previous electrophysiologic studies. At least in this model, the nodule does not appear to be responsible for enhanced excitability (or, presumably, seizure initiation). Excitability is different in tissue that contains a nodule, suggesting altered network function, perhaps reflecting the abnormal developmental pattern that gave rise to the nodule.",
keywords = "c-fos, Dysplasia, Epileptogenicity, Nodular heterotopia, Organotypic slice cultures, Seizure initiation",
author = "Doisy, {Emily T.} and Wenzel, {H. J{\"u}rgen} and Yi Mu and Nguyen, {Danh V.} and Schwartzkroin, {Philip A}",
year = "2015",
month = "4",
day = "1",
doi = "10.1111/epi.12945",
language = "English (US)",
volume = "56",
pages = "626--635",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Nodule excitability in an animal model of periventricular nodular heterotopia

T2 - C-fos activation in organotypic hippocampal slices

AU - Doisy, Emily T.

AU - Wenzel, H. Jürgen

AU - Mu, Yi

AU - Nguyen, Danh V.

AU - Schwartzkroin, Philip A

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Summary Objective Aberrations in brain development may lead to dysplastic structures such as periventricular nodules. Although these abnormal collections of neurons are often associated with difficult-to-control seizure activity, there is little consensus regarding the epileptogenicity of the nodules themselves. Because one common treatment option is surgical resection of suspected epileptic nodules, it is important to determine whether these structures in fact give rise, or essentially contribute, to epileptic activities. Methods To study the excitability of aberrant nodules, we have examined c-fos activation in organotypic hippocampal slice cultures generated from an animal model of periventricular nodular heterotopia created by treating pregnant rats with methylazoxymethanol acetate. Using this preparation, we have also attempted to assess tissue excitability when the nodule is surgically removed from the culture. We then compared c-fos activation in this in vitro preparation to c-fos activation generated in an intact rat treated with kainic acid. Results Quantitative analysis of c-fos activation failed to show enhanced nodule excitability compared to neocortex or CA1 hippocampus. However, when we compared cultures with and without a nodule, presence of a nodule did affect the excitability of CA1 and cortex, at least as reflected in c-fos labeling. Surgical removal of the nodule did not result in a consistent decrease in excitability as reflected in the c-fos biomarker. Significance Our results from the organotypic culture were generally consistent with our observations on excitability in the intact rat - as seen not only with c-fos but also in previous electrophysiologic studies. At least in this model, the nodule does not appear to be responsible for enhanced excitability (or, presumably, seizure initiation). Excitability is different in tissue that contains a nodule, suggesting altered network function, perhaps reflecting the abnormal developmental pattern that gave rise to the nodule.

AB - Summary Objective Aberrations in brain development may lead to dysplastic structures such as periventricular nodules. Although these abnormal collections of neurons are often associated with difficult-to-control seizure activity, there is little consensus regarding the epileptogenicity of the nodules themselves. Because one common treatment option is surgical resection of suspected epileptic nodules, it is important to determine whether these structures in fact give rise, or essentially contribute, to epileptic activities. Methods To study the excitability of aberrant nodules, we have examined c-fos activation in organotypic hippocampal slice cultures generated from an animal model of periventricular nodular heterotopia created by treating pregnant rats with methylazoxymethanol acetate. Using this preparation, we have also attempted to assess tissue excitability when the nodule is surgically removed from the culture. We then compared c-fos activation in this in vitro preparation to c-fos activation generated in an intact rat treated with kainic acid. Results Quantitative analysis of c-fos activation failed to show enhanced nodule excitability compared to neocortex or CA1 hippocampus. However, when we compared cultures with and without a nodule, presence of a nodule did affect the excitability of CA1 and cortex, at least as reflected in c-fos labeling. Surgical removal of the nodule did not result in a consistent decrease in excitability as reflected in the c-fos biomarker. Significance Our results from the organotypic culture were generally consistent with our observations on excitability in the intact rat - as seen not only with c-fos but also in previous electrophysiologic studies. At least in this model, the nodule does not appear to be responsible for enhanced excitability (or, presumably, seizure initiation). Excitability is different in tissue that contains a nodule, suggesting altered network function, perhaps reflecting the abnormal developmental pattern that gave rise to the nodule.

KW - c-fos

KW - Dysplasia

KW - Epileptogenicity

KW - Nodular heterotopia

KW - Organotypic slice cultures

KW - Seizure initiation

UR - http://www.scopus.com/inward/record.url?scp=84927570334&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84927570334&partnerID=8YFLogxK

U2 - 10.1111/epi.12945

DO - 10.1111/epi.12945

M3 - Article

VL - 56

SP - 626

EP - 635

JO - Epilepsia

JF - Epilepsia

SN - 0013-9580

IS - 4

ER -