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Successful protection by amantadine hydrochloride against lethal encephalitis caused by a highly neurovirulent recombinant influenza A virus in mice.

Abstract：

:A mouse model system for a lethal encephalitis due to influenza has been established by stereotaxic microinjection with the recombinant R404BP strain of influenza A virus into the olfactory bulb of C57BL/6 mice. The virus infection spread selectively to neurons in nuclei of the broad areas of the brain parenchyma that have anatomical connections to the olfactory bulb, leading to apoptotic neurodegeneration. The inflammatory reaction at the extended stage of viral infection involved the vascular structures affected by induction of inducible nitric oxide synthase and protein nitration; those were related to the etiology of fatal brain edema. The intraperitoneal administration of amantadine inhibited the viral growth in the brain and saved mice from the lethal encephalitis. The severity of neuronal loss paralleled the time lag between the virus challenge and the start of amantadine treatment. Thus, early pharmacological intervention is essential to minimize neurological deficits due to influenza virus-induced neurodegeneration.

journal_name

Virology

journal_title

Virology

authors

Mori I,Liu B,Hossain MJ,Takakuwa H,Daikoku T,Nishiyama Y,Naiki H,Matsumoto K,Yokochi T,Kimura Y

doi

10.1006/viro.2002.1601

subject

Has Abstract

pub_date

2002-11-25 00:00:00

pages

287-96

issue

2

eissn

0042-6822

issn

1096-0341

pii

S0042682202916016

journal_volume

303

pub_type

杂志文章

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