Human neural stem cell transplantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticus in adult rats

Kon Chu, Manho Kim, Keun Hwa Jung, Daejong Jeon, Soon Tae Lee, Juhyun Kim, Sang Wuk Jeong, Seung Up Kim, Sang Kun Lee, Hee Sup Shin, Jae Kyu Roh

Research output: Contribution to journalArticle

Abstract

Transplantation of neural stem cells (NSCs) can replace lost neurons and improve the functional deficits. Cell transplantation strategies have been tried in the epileptic disorder, but the effect of exogenous NSCs is unknown. In this study, we attempted to test the anti-epileptogenic effect of NSCs in adult rats with status epilepticus. Experimental status epilepticus was induced by lithium-pilocarpine injection, and β galactosidase-encoded human NSCs were transplanted intravenously on the next day of status epilepticus. Spontaneous recurrent seizures were monitored with Racine's seizure severity scale. Immunohistochemistry with anti-β gal, Tuj-1, NeuN, GFAP, CNPase, GluR2, parvalbumin, and GABA were performed and extracellular field excitatory postsynaptic potentials (fEPSP) were recorded. Human NSCs suppressed spontaneous recurrent seizure formation and transplanted NSCs were differentiated into GABA-immunoreactive interneurons in the damaged hippocampus. Amplitude of fEPSP in the hippocampal CA1 was reduced, which was reversed by picrotoxin. These findings suggest that NSCs could be differentiated into inhibitory interneurons and decrease neuronal excitability, which could prevent spontaneous recurrent seizure formation in adult rats with pilocarpine-induced status epilepticus.

Original languageEnglish (US)
Pages (from-to)213-221
Number of pages9
JournalBrain research
Volume1023
Issue number2
DOIs
StatePublished - Oct 15 2004
Externally publishedYes

Fingerprint

Pilocarpine
Neural Stem Cells
Status Epilepticus
Stem Cell Transplantation
Seizures
Excitatory Postsynaptic Potentials
Interneurons
gamma-Aminobutyric Acid
2',3'-Cyclic-Nucleotide Phosphodiesterases
Galactosidases
Parvalbumins
Picrotoxin
Cell Transplantation
Lithium
Hippocampus
Transplantation
Immunohistochemistry
Neurons
Injections

Keywords

  • Epilepsy
  • Epileptogenesis
  • GABA
  • Inhibition
  • Interneuron
  • Neural stem cell

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Human neural stem cell transplantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticus in adult rats. / Chu, Kon; Kim, Manho; Jung, Keun Hwa; Jeon, Daejong; Lee, Soon Tae; Kim, Juhyun; Jeong, Sang Wuk; Kim, Seung Up; Lee, Sang Kun; Shin, Hee Sup; Roh, Jae Kyu.

In: Brain research, Vol. 1023, No. 2, 15.10.2004, p. 213-221.

Research output: Contribution to journalArticle

Chu, Kon ; Kim, Manho ; Jung, Keun Hwa ; Jeon, Daejong ; Lee, Soon Tae ; Kim, Juhyun ; Jeong, Sang Wuk ; Kim, Seung Up ; Lee, Sang Kun ; Shin, Hee Sup ; Roh, Jae Kyu. / Human neural stem cell transplantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticus in adult rats. In: Brain research. 2004 ; Vol. 1023, No. 2. pp. 213-221.
@article{a9b86b5ea02d445081b444bf03c393f7,
title = "Human neural stem cell transplantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticus in adult rats",
abstract = "Transplantation of neural stem cells (NSCs) can replace lost neurons and improve the functional deficits. Cell transplantation strategies have been tried in the epileptic disorder, but the effect of exogenous NSCs is unknown. In this study, we attempted to test the anti-epileptogenic effect of NSCs in adult rats with status epilepticus. Experimental status epilepticus was induced by lithium-pilocarpine injection, and β galactosidase-encoded human NSCs were transplanted intravenously on the next day of status epilepticus. Spontaneous recurrent seizures were monitored with Racine's seizure severity scale. Immunohistochemistry with anti-β gal, Tuj-1, NeuN, GFAP, CNPase, GluR2, parvalbumin, and GABA were performed and extracellular field excitatory postsynaptic potentials (fEPSP) were recorded. Human NSCs suppressed spontaneous recurrent seizure formation and transplanted NSCs were differentiated into GABA-immunoreactive interneurons in the damaged hippocampus. Amplitude of fEPSP in the hippocampal CA1 was reduced, which was reversed by picrotoxin. These findings suggest that NSCs could be differentiated into inhibitory interneurons and decrease neuronal excitability, which could prevent spontaneous recurrent seizure formation in adult rats with pilocarpine-induced status epilepticus.",
keywords = "Epilepsy, Epileptogenesis, GABA, Inhibition, Interneuron, Neural stem cell",
author = "Kon Chu and Manho Kim and Jung, {Keun Hwa} and Daejong Jeon and Lee, {Soon Tae} and Juhyun Kim and Jeong, {Sang Wuk} and Kim, {Seung Up} and Lee, {Sang Kun} and Shin, {Hee Sup} and Roh, {Jae Kyu}",
year = "2004",
month = "10",
day = "15",
doi = "10.1016/j.brainres.2004.07.045",
language = "English (US)",
volume = "1023",
pages = "213--221",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Human neural stem cell transplantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticus in adult rats

AU - Chu, Kon

AU - Kim, Manho

AU - Jung, Keun Hwa

AU - Jeon, Daejong

AU - Lee, Soon Tae

AU - Kim, Juhyun

AU - Jeong, Sang Wuk

AU - Kim, Seung Up

AU - Lee, Sang Kun

AU - Shin, Hee Sup

AU - Roh, Jae Kyu

PY - 2004/10/15

Y1 - 2004/10/15

N2 - Transplantation of neural stem cells (NSCs) can replace lost neurons and improve the functional deficits. Cell transplantation strategies have been tried in the epileptic disorder, but the effect of exogenous NSCs is unknown. In this study, we attempted to test the anti-epileptogenic effect of NSCs in adult rats with status epilepticus. Experimental status epilepticus was induced by lithium-pilocarpine injection, and β galactosidase-encoded human NSCs were transplanted intravenously on the next day of status epilepticus. Spontaneous recurrent seizures were monitored with Racine's seizure severity scale. Immunohistochemistry with anti-β gal, Tuj-1, NeuN, GFAP, CNPase, GluR2, parvalbumin, and GABA were performed and extracellular field excitatory postsynaptic potentials (fEPSP) were recorded. Human NSCs suppressed spontaneous recurrent seizure formation and transplanted NSCs were differentiated into GABA-immunoreactive interneurons in the damaged hippocampus. Amplitude of fEPSP in the hippocampal CA1 was reduced, which was reversed by picrotoxin. These findings suggest that NSCs could be differentiated into inhibitory interneurons and decrease neuronal excitability, which could prevent spontaneous recurrent seizure formation in adult rats with pilocarpine-induced status epilepticus.

AB - Transplantation of neural stem cells (NSCs) can replace lost neurons and improve the functional deficits. Cell transplantation strategies have been tried in the epileptic disorder, but the effect of exogenous NSCs is unknown. In this study, we attempted to test the anti-epileptogenic effect of NSCs in adult rats with status epilepticus. Experimental status epilepticus was induced by lithium-pilocarpine injection, and β galactosidase-encoded human NSCs were transplanted intravenously on the next day of status epilepticus. Spontaneous recurrent seizures were monitored with Racine's seizure severity scale. Immunohistochemistry with anti-β gal, Tuj-1, NeuN, GFAP, CNPase, GluR2, parvalbumin, and GABA were performed and extracellular field excitatory postsynaptic potentials (fEPSP) were recorded. Human NSCs suppressed spontaneous recurrent seizure formation and transplanted NSCs were differentiated into GABA-immunoreactive interneurons in the damaged hippocampus. Amplitude of fEPSP in the hippocampal CA1 was reduced, which was reversed by picrotoxin. These findings suggest that NSCs could be differentiated into inhibitory interneurons and decrease neuronal excitability, which could prevent spontaneous recurrent seizure formation in adult rats with pilocarpine-induced status epilepticus.

KW - Epilepsy

KW - Epileptogenesis

KW - GABA

KW - Inhibition

KW - Interneuron

KW - Neural stem cell

UR - http://www.scopus.com/inward/record.url?scp=4544290431&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4544290431&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2004.07.045

DO - 10.1016/j.brainres.2004.07.045

M3 - Article

C2 - 15374747

AN - SCOPUS:4544290431

VL - 1023

SP - 213

EP - 221

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 2

ER -