title: Seizure, neuron loss, and mossy fiber sprouting in herpes simplex virus type 1-infected organotypic hippocampal cultures.
abstract: OBJECTIVE
  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 x 10(5) 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 afterhyperpolarization 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.
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan.
authors.forename: Su-Fen
authors.initials: SF
authors.lastname: Chen
authors.forename: Chiung-Chun
authors.initials: CC
authors.lastname: Huang
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Wu
authors.forename: Shun-Hua
authors.initials: SH
authors.lastname: Chen
authors.forename: Ying-Ching
authors.initials: YC
authors.lastname: Liang
authors.forename: Kuei-Sen
authors.initials: KS
authors.lastname: Hsu
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D016923:Cell Death; D006561:Herpes Simplex / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000302:isolation & purification; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000473:pathology / Q000821:virology*; D009474:Neurons / Q000473:pathology* / Q000821:virology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000473:pathology* / Q000503:physiopathology / Q000821:virology*