Seizure, neuron loss, and mossy fiber sprouting in herpes simplex virus type 1-Infected organotypic hippocampal cultures

被引:33
作者
Chen, SF
Huang, CC
Wu, TM
Chen, SH
Liang, YC
Hsu, KS
机构
[1] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 701, Taiwan
[2] Natl Cheng Kung Univ, Inst Basic Med Sci, Tainan 701, Taiwan
[3] Natl Cheng Kung Univ, Dept Microbiol & Immunol, Tainan 701, Taiwan
关键词
herpes simplex virus; epilepsy; hippocampus; Mossy fiber sprouting; organotypic slice culture;
D O I
10.1111/j.0013-9580.2004.37403.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Purpose: Epileptic seizures are frequently seen after viral encephalitis. Herpes simplex virus type I (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 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.
引用
收藏
页码:322 / 332
页数:11
相关论文
共 44 条
  • [1] THE RISK OF UNPROVOKED SEIZURES AFTER ENCEPHALITIS AND MENINGITIS
    ANNEGERS, JF
    HAUSER, WA
    BEGHI, E
    NICOLOSI, A
    KURLAND, LT
    [J]. NEUROLOGY, 1988, 38 (09) : 1407 - 1410
  • [2] Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro
    Avoli, M
    D'Antuono, M
    Louvel, J
    Köhling, R
    Biagini, G
    Pumain, R
    D'Arcangelo, G
    Tancredi, V
    [J]. PROGRESS IN NEUROBIOLOGY, 2002, 68 (03) : 167 - 207
  • [3] HERPES-SIMPLEX VIRUS GENOMES IN HUMAN NERVOUS-SYSTEM TISSUE ANALYZED BY POLYMERASE CHAIN-REACTION
    BARINGER, JR
    PISANI, P
    [J]. ANNALS OF NEUROLOGY, 1994, 36 (06) : 823 - 829
  • [4] CAVAZOS JE, 1991, J NEUROSCI, V11, P2795
  • [5] SENSITIVITY OF ARABINOSYLADENINE-RESISTANT MUTANTS OF HERPES-SIMPLEX VIRUS TO OTHER ANTIVIRAL DRUGS AND MAPPING OF DRUG HYPERSENSITIVITY MUTATIONS TO THE DNA-POLYMERASE LOCUS
    COEN, DM
    FLEMING, HE
    LESLIE, LK
    RETONDO, MJ
    [J]. JOURNAL OF VIROLOGY, 1985, 53 (02) : 477 - 488
  • [6] FACTORS INFLUENCING MOSSY FIBER COLLATERAL SPROUTING IN ORGANOTYPIC SLICE CULTURES OF NEONATAL MOUSE HIPPOCAMPUS
    COLTMAN, BW
    EARLEY, EM
    SHAHAR, A
    DUDEK, FE
    IDE, CF
    [J]. JOURNAL OF COMPARATIVE NEUROLOGY, 1995, 362 (02) : 209 - 222
  • [7] EXPLANATION FOR THE LOCALIZATION OF HERPES-SIMPLEX ENCEPHALITIS
    DAVIS, LE
    JOHNSON, RT
    [J]. ANNALS OF NEUROLOGY, 1979, 5 (01) : 2 - 5
  • [8] Acyclic/carbocyclic guanosine analogues as anti-herpesvirus agents
    De Clercq, E
    Andrei, G
    Snoeck, R
    De Bolle, L
    Naesens, L
    Degrève, B
    Balzarini, J
    Zhang, Y
    Schols, D
    Leyssen, P
    Ying, C
    Neyts, J
    [J]. NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, 2001, 20 (4-7) : 271 - 285
  • [9] DEGRAAF AS, 1974, EPILEPSIA, V15, P291