Seizure, Neuron Loss, and Mossy Fiber Sprouting in Herpes Simplex Virus Type 1-Infected Organotypic Hippocampal Cultures

Su Fen Chen, Chiung Chun Huang, Hung Ming Wu, Shun-hua Chen, Ying Ching Liang, Kuei-Sen Hsu

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Purpose: Epileptic seizures are frequently seen after viral encephalitis. Herpes simplex virus type 1 (HSV-1) encephalitis is the most common cause of acquired epilepsy in humans. However, little information is available about the neuropathogenesis of HSV-1-associated seizures. We have developed an in vitro HSV-1-infected organotypic hippocampal slice culture to elucidate the underlying mechanisms of HSV-1-associated acute seizure activity. Methods: Hippocampal slice cultures were prepared from postnatal day 10 to 12 rat pups. Wild-type HSV-1 strain RE (1 × 105 PFU) was applied to cultures at 14 days in vitro. The excitability of CA3 pyramidal cells and hippocampal network properties were measured with electrophysiological recordings. Hematoxylin-eosin (H&E) and Timm stains were used. Results: HSV-1 infection induces epileptiform activity, neuron loss, and subsequently a dramatic increase of mossy fiber sprouting in the supragranular area. With intracellular recordings, surviving CA3 pyramidal cells exhibited a more depolarizing resting membrane potential concomitant with an increase in membrane input resistance and had a lower threshold to generate synchronized bursts and a decrease in the amplitude of after-hyperpolarization than did controls. When the antiherpes agent acyclovir was applied with a delay of 1 or 24 h after HSV-1 infection, a dramatic inhibition of HSV-1 replication and protection of the neuron loss were observed. Conclusions: These results suggest that a direct change in the excitability of the hippocampal CA3 neuronal network and HSV-1-induced neuron loss resulting in subsequent mossy fiber reorganization may play an important role in the generation of epileptiform activity.

Original languageEnglish
Pages (from-to)322-332
Number of pages11
JournalEpilepsia
Volume45
Issue number4
DOIs
Publication statusPublished - 2004 Apr 1

Fingerprint

Human Herpesvirus 1
Seizures
Neurons
Pyramidal Cells
Virus Diseases
Epilepsy
Viral Encephalitis
Acyclovir
Encephalitis
Hematoxylin
Eosine Yellowish-(YS)
Virus Replication
Membrane Potentials
Coloring Agents
Membranes

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Chen, Su Fen ; Huang, Chiung Chun ; Wu, Hung Ming ; Chen, Shun-hua ; Liang, Ying Ching ; Hsu, Kuei-Sen. / Seizure, Neuron Loss, and Mossy Fiber Sprouting in Herpes Simplex Virus Type 1-Infected Organotypic Hippocampal Cultures. In: Epilepsia. 2004 ; Vol. 45, No. 4. pp. 322-332.
@article{c8ac33bb75044ce492408fce028c2d51,
title = "Seizure, Neuron Loss, and Mossy Fiber Sprouting in Herpes Simplex Virus Type 1-Infected Organotypic Hippocampal Cultures",
abstract = "Purpose: Epileptic seizures are frequently seen after viral encephalitis. Herpes simplex virus type 1 (HSV-1) encephalitis is the most common cause of acquired epilepsy in humans. However, little information is available about the neuropathogenesis of HSV-1-associated seizures. We have developed an in vitro HSV-1-infected organotypic hippocampal slice culture to elucidate the underlying mechanisms of HSV-1-associated acute seizure activity. Methods: Hippocampal slice cultures were prepared from postnatal day 10 to 12 rat pups. Wild-type HSV-1 strain RE (1 × 105 PFU) was applied to cultures at 14 days in vitro. The excitability of CA3 pyramidal cells and hippocampal network properties were measured with electrophysiological recordings. Hematoxylin-eosin (H&E) and Timm stains were used. Results: HSV-1 infection induces epileptiform activity, neuron loss, and subsequently a dramatic increase of mossy fiber sprouting in the supragranular area. With intracellular recordings, surviving CA3 pyramidal cells exhibited a more depolarizing resting membrane potential concomitant with an increase in membrane input resistance and had a lower threshold to generate synchronized bursts and a decrease in the amplitude of after-hyperpolarization than did controls. When the antiherpes agent acyclovir was applied with a delay of 1 or 24 h after HSV-1 infection, a dramatic inhibition of HSV-1 replication and protection of the neuron loss were observed. Conclusions: These results suggest that a direct change in the excitability of the hippocampal CA3 neuronal network and HSV-1-induced neuron loss resulting in subsequent mossy fiber reorganization may play an important role in the generation of epileptiform activity.",
author = "Chen, {Su Fen} and Huang, {Chiung Chun} and Wu, {Hung Ming} and Shun-hua Chen and Liang, {Ying Ching} and Kuei-Sen Hsu",
year = "2004",
month = "4",
day = "1",
doi = "10.1111/j.0013-9580.2004.37403.x",
language = "English",
volume = "45",
pages = "322--332",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "4",

}

Seizure, Neuron Loss, and Mossy Fiber Sprouting in Herpes Simplex Virus Type 1-Infected Organotypic Hippocampal Cultures. / Chen, Su Fen; Huang, Chiung Chun; Wu, Hung Ming; Chen, Shun-hua; Liang, Ying Ching; Hsu, Kuei-Sen.

In: Epilepsia, Vol. 45, No. 4, 01.04.2004, p. 322-332.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Seizure, Neuron Loss, and Mossy Fiber Sprouting in Herpes Simplex Virus Type 1-Infected Organotypic Hippocampal Cultures

AU - Chen, Su Fen

AU - Huang, Chiung Chun

AU - Wu, Hung Ming

AU - Chen, Shun-hua

AU - Liang, Ying Ching

AU - Hsu, Kuei-Sen

PY - 2004/4/1

Y1 - 2004/4/1

N2 - Purpose: Epileptic seizures are frequently seen after viral encephalitis. Herpes simplex virus type 1 (HSV-1) encephalitis is the most common cause of acquired epilepsy in humans. However, little information is available about the neuropathogenesis of HSV-1-associated seizures. We have developed an in vitro HSV-1-infected organotypic hippocampal slice culture to elucidate the underlying mechanisms of HSV-1-associated acute seizure activity. Methods: Hippocampal slice cultures were prepared from postnatal day 10 to 12 rat pups. Wild-type HSV-1 strain RE (1 × 105 PFU) was applied to cultures at 14 days in vitro. The excitability of CA3 pyramidal cells and hippocampal network properties were measured with electrophysiological recordings. Hematoxylin-eosin (H&E) and Timm stains were used. Results: HSV-1 infection induces epileptiform activity, neuron loss, and subsequently a dramatic increase of mossy fiber sprouting in the supragranular area. With intracellular recordings, surviving CA3 pyramidal cells exhibited a more depolarizing resting membrane potential concomitant with an increase in membrane input resistance and had a lower threshold to generate synchronized bursts and a decrease in the amplitude of after-hyperpolarization than did controls. When the antiherpes agent acyclovir was applied with a delay of 1 or 24 h after HSV-1 infection, a dramatic inhibition of HSV-1 replication and protection of the neuron loss were observed. Conclusions: These results suggest that a direct change in the excitability of the hippocampal CA3 neuronal network and HSV-1-induced neuron loss resulting in subsequent mossy fiber reorganization may play an important role in the generation of epileptiform activity.

AB - Purpose: Epileptic seizures are frequently seen after viral encephalitis. Herpes simplex virus type 1 (HSV-1) encephalitis is the most common cause of acquired epilepsy in humans. However, little information is available about the neuropathogenesis of HSV-1-associated seizures. We have developed an in vitro HSV-1-infected organotypic hippocampal slice culture to elucidate the underlying mechanisms of HSV-1-associated acute seizure activity. Methods: Hippocampal slice cultures were prepared from postnatal day 10 to 12 rat pups. Wild-type HSV-1 strain RE (1 × 105 PFU) was applied to cultures at 14 days in vitro. The excitability of CA3 pyramidal cells and hippocampal network properties were measured with electrophysiological recordings. Hematoxylin-eosin (H&E) and Timm stains were used. Results: HSV-1 infection induces epileptiform activity, neuron loss, and subsequently a dramatic increase of mossy fiber sprouting in the supragranular area. With intracellular recordings, surviving CA3 pyramidal cells exhibited a more depolarizing resting membrane potential concomitant with an increase in membrane input resistance and had a lower threshold to generate synchronized bursts and a decrease in the amplitude of after-hyperpolarization than did controls. When the antiherpes agent acyclovir was applied with a delay of 1 or 24 h after HSV-1 infection, a dramatic inhibition of HSV-1 replication and protection of the neuron loss were observed. Conclusions: These results suggest that a direct change in the excitability of the hippocampal CA3 neuronal network and HSV-1-induced neuron loss resulting in subsequent mossy fiber reorganization may play an important role in the generation of epileptiform activity.

UR - http://www.scopus.com/inward/record.url?scp=1842831177&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1842831177&partnerID=8YFLogxK

U2 - 10.1111/j.0013-9580.2004.37403.x

DO - 10.1111/j.0013-9580.2004.37403.x

M3 - Article

VL - 45

SP - 322

EP - 332

JO - Epilepsia

JF - Epilepsia

SN - 0013-9580

IS - 4

ER -