Seizure, neuron loss, and mossy fiber sprouting in herpes simplex virus type 1-infected organotypic hippocampal cultures.
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.
Chen
Su-Fen
SF
Department of Pharmacology, Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan.
Huang
Chiung-Chun
CC
Wu
Hung-Ming
HM
Chen
Shun-Hua
SH
Liang
Ying-Ching
YC
Hsu
Kuei-Sen
KS
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*