Molecular alterations underlying epileptogenesis after prolonged febrile seizure and modulation by erythropoietin

Keun Hwa Jung, Kon Chu, Soon Tae Lee, Kyung Il Park, Jin Hee Kim, Kyung Muk Kang, Soyun Kim, Daejong Jeon, Manho Kim, Sang Kun Lee, Jae Kyu Roh

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Purpose: Children who experience complex febrile seizures are at a higher risk of subsequent epileptic episodes, and they may require therapy. This issue can be resolved by interventional studies using molecular targets identified and defined in animal models. In the current study, the molecular changes in the rat brain after febrile seizures were examined throughout the latent period, and erythropoietin was administered as a potentially antiepileptogenic intervention. Methods: The changes in the expressions of genes that were differentially regulated during the latent period after febrile seizures were categorized into the following four patterns: (1) continuously high (CH); (2) continuously low (CL); (3) rise and fall (RF); and (4) going-up (GU). Erythropoietin was administered immediately after seizure cessation and then once daily for at most 7 days, and spontaneous recurrent seizures and cellular and molecular changes were investigated. Key Findings: The CH genes were associated with cell cycle and adhesion, whereas the CL genes were related to energy metabolism. Within the category of RF, the largest changes were for genes involved in inflammation, apoptosis, and c-aminobutyric acid (GABA) signaling. The GU category included genes involved in ion transport and synaptogenesis. Along with an early rise in inflammatory genes, there were substantial increases in brain edema and activated microglia during the early latent period. Erythropoietin reduced the early inflammatory responses and modulated the molecular alterations after febrile seizures, thereby reducing the risk of subsequent spontaneous seizures. Significance: Erythropoietin treatment may provide a new strategy for preventing epilepsy in susceptible individuals with atypical febrile seizures. Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)541-550
Number of pages10
JournalEpilepsia
Volume52
Issue number3
DOIs
StatePublished - 1 Mar 2011

Fingerprint

Febrile Seizures
Erythropoietin
Seizures
Genes
Aminobutyrates
Ion Transport
Brain Edema
Microglia
Cell Adhesion
gamma-Aminobutyric Acid
Energy Metabolism
Epilepsy
Cell Cycle
Animal Models
Apoptosis
Inflammation
Gene Expression
Brain

Keywords

  • Epilepsy
  • Epileptogenesis
  • Erythropoietin
  • Febrile seizure
  • Inflammation

Cite this

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title = "Molecular alterations underlying epileptogenesis after prolonged febrile seizure and modulation by erythropoietin",
abstract = "Purpose: Children who experience complex febrile seizures are at a higher risk of subsequent epileptic episodes, and they may require therapy. This issue can be resolved by interventional studies using molecular targets identified and defined in animal models. In the current study, the molecular changes in the rat brain after febrile seizures were examined throughout the latent period, and erythropoietin was administered as a potentially antiepileptogenic intervention. Methods: The changes in the expressions of genes that were differentially regulated during the latent period after febrile seizures were categorized into the following four patterns: (1) continuously high (CH); (2) continuously low (CL); (3) rise and fall (RF); and (4) going-up (GU). Erythropoietin was administered immediately after seizure cessation and then once daily for at most 7 days, and spontaneous recurrent seizures and cellular and molecular changes were investigated. Key Findings: The CH genes were associated with cell cycle and adhesion, whereas the CL genes were related to energy metabolism. Within the category of RF, the largest changes were for genes involved in inflammation, apoptosis, and c-aminobutyric acid (GABA) signaling. The GU category included genes involved in ion transport and synaptogenesis. Along with an early rise in inflammatory genes, there were substantial increases in brain edema and activated microglia during the early latent period. Erythropoietin reduced the early inflammatory responses and modulated the molecular alterations after febrile seizures, thereby reducing the risk of subsequent spontaneous seizures. Significance: Erythropoietin treatment may provide a new strategy for preventing epilepsy in susceptible individuals with atypical febrile seizures. Wiley Periodicals, Inc.",
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author = "Jung, {Keun Hwa} and Kon Chu and Lee, {Soon Tae} and Park, {Kyung Il} and Kim, {Jin Hee} and Kang, {Kyung Muk} and Soyun Kim and Daejong Jeon and Manho Kim and Lee, {Sang Kun} and Roh, {Jae Kyu}",
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Molecular alterations underlying epileptogenesis after prolonged febrile seizure and modulation by erythropoietin. / Jung, Keun Hwa; Chu, Kon; Lee, Soon Tae; Park, Kyung Il; Kim, Jin Hee; Kang, Kyung Muk; Kim, Soyun; Jeon, Daejong; Kim, Manho; Lee, Sang Kun; Roh, Jae Kyu.

In: Epilepsia, Vol. 52, No. 3, 01.03.2011, p. 541-550.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Molecular alterations underlying epileptogenesis after prolonged febrile seizure and modulation by erythropoietin

AU - Jung, Keun Hwa

AU - Chu, Kon

AU - Lee, Soon Tae

AU - Park, Kyung Il

AU - Kim, Jin Hee

AU - Kang, Kyung Muk

AU - Kim, Soyun

AU - Jeon, Daejong

AU - Kim, Manho

AU - Lee, Sang Kun

AU - Roh, Jae Kyu

PY - 2011/3/1

Y1 - 2011/3/1

N2 - Purpose: Children who experience complex febrile seizures are at a higher risk of subsequent epileptic episodes, and they may require therapy. This issue can be resolved by interventional studies using molecular targets identified and defined in animal models. In the current study, the molecular changes in the rat brain after febrile seizures were examined throughout the latent period, and erythropoietin was administered as a potentially antiepileptogenic intervention. Methods: The changes in the expressions of genes that were differentially regulated during the latent period after febrile seizures were categorized into the following four patterns: (1) continuously high (CH); (2) continuously low (CL); (3) rise and fall (RF); and (4) going-up (GU). Erythropoietin was administered immediately after seizure cessation and then once daily for at most 7 days, and spontaneous recurrent seizures and cellular and molecular changes were investigated. Key Findings: The CH genes were associated with cell cycle and adhesion, whereas the CL genes were related to energy metabolism. Within the category of RF, the largest changes were for genes involved in inflammation, apoptosis, and c-aminobutyric acid (GABA) signaling. The GU category included genes involved in ion transport and synaptogenesis. Along with an early rise in inflammatory genes, there were substantial increases in brain edema and activated microglia during the early latent period. Erythropoietin reduced the early inflammatory responses and modulated the molecular alterations after febrile seizures, thereby reducing the risk of subsequent spontaneous seizures. Significance: Erythropoietin treatment may provide a new strategy for preventing epilepsy in susceptible individuals with atypical febrile seizures. Wiley Periodicals, Inc.

AB - Purpose: Children who experience complex febrile seizures are at a higher risk of subsequent epileptic episodes, and they may require therapy. This issue can be resolved by interventional studies using molecular targets identified and defined in animal models. In the current study, the molecular changes in the rat brain after febrile seizures were examined throughout the latent period, and erythropoietin was administered as a potentially antiepileptogenic intervention. Methods: The changes in the expressions of genes that were differentially regulated during the latent period after febrile seizures were categorized into the following four patterns: (1) continuously high (CH); (2) continuously low (CL); (3) rise and fall (RF); and (4) going-up (GU). Erythropoietin was administered immediately after seizure cessation and then once daily for at most 7 days, and spontaneous recurrent seizures and cellular and molecular changes were investigated. Key Findings: The CH genes were associated with cell cycle and adhesion, whereas the CL genes were related to energy metabolism. Within the category of RF, the largest changes were for genes involved in inflammation, apoptosis, and c-aminobutyric acid (GABA) signaling. The GU category included genes involved in ion transport and synaptogenesis. Along with an early rise in inflammatory genes, there were substantial increases in brain edema and activated microglia during the early latent period. Erythropoietin reduced the early inflammatory responses and modulated the molecular alterations after febrile seizures, thereby reducing the risk of subsequent spontaneous seizures. Significance: Erythropoietin treatment may provide a new strategy for preventing epilepsy in susceptible individuals with atypical febrile seizures. Wiley Periodicals, Inc.

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KW - Erythropoietin

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