PATHOGENESIS OF INFLUENZAL ENCEPHALITIS/ENCEPHALOPATHY

流感脑炎/脑病的发病机制

• 批准号: 14360182
• 负责人: UMEMURA Takashi
• 金额: $ 9.54万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14360182/
• 关键词: Influenza; Influenza virus; Influenzal encephalopathy; Aujezky virus; Transneural Spread; Viral encephalitis; Intrathecal vaccination; Reye's syndrome; トリインフルエンザウイルス; H5N1; 持続感染; 解熱剤; 経神経感染; ボルタレン; 迷走神経切除; アスピリン; インフルエンザ脳炎; 脳症

Demonstration of neural spread of influenza virus(IFV)Intranasally inoculated highly pathogenic IFV to mice invaded medulla oblongata and thoracic cord possibly via vagal and/or sympathetic nerves (Vet Microbiol,2003). Inoculation of IFV to unilaterally vagectomized mice demonstrated the virus invades brain stem through vagal nerve(Vet Pathol,2004). Transneural transmission of IFV was examined using compartmentalized cultures of neurons from mouse dorsal root ganglia, the results were compared with those obtained using the pseudorabies virus. The results indicated that IFV can be spread transneurally and the transmission is independent of axonal transport using microtubules (J Gen Viral,2005).Persistent infection of IFVViral antigen, viral genomes and encephalitis persisted for not longer than 48 days in mice brain after intranasal inoculation of IFV. However the virus was not recovered from the brain.Experimental reproduction of Reyes' s syndromeThe cause of Reye's syndrome, acute enc … More ephalopathy of childhood is suspected of IFV infection and antipyretic treatment. The effects of antipyretics (aspirin and voltaren) on avian and murine models of influenzal encephalitis/encephalopathy were examined. Antipyretic treatment did not affect murine model (transneural spread model of IFV), whereas the treatment enhanced avian encephalitis/encephalopathy (hematogeneous spread model of IFV). Voltaren exaggerated the lesion more prominently than aspirin(J Vet Med Sci,2004).Intrathecal immunizationInactivated IFV or Aujezky virus were inoculated intrathecally (inoculation into cerebrospinal fluid) or subcutaneously in rabbits and mice. Antibody in cerebrospinal fluid was raised only by intrathecal immunization. Intrathecal immunization using inactivated Aujezky virus protected mice completely from clinical signs, pathological changes and death due to intramuscular inoculation of Aujezky virus. The results indicated the efficacy of intrathecal immunization against the viruses which invade central nervous system from invasion sites through the peripheral nerves. Less

流感病毒（IFV）神经传播的证明：经鼻内接种的高致病性IFV可能通过迷走神经和/或交感神经侵入延髓和胸髓（Vet Microbiol,2003）。将IFV接种于单侧阴道切除的小鼠，表明病毒通过迷走神经侵入脑干（Vet Pathol,2004）。利用小鼠背根神经节神经元区室化培养物检测IFV的跨神经传递，并将结果与伪狂犬病毒的结果进行比较。结果表明，IFV可以经神经传播，并且传播不依赖于利用微管的轴突运输（J Gen Viral,2005）。鼻内接种IFV后，小鼠脑内持续感染IFV病毒抗原、病毒基因组和脑炎的时间不超过48天。然而，病毒并没有从大脑中恢复。雷氏综合征的病因，急性enc多怀疑儿童期脑病为IFV感染及退热治疗。研究了退烧药（阿司匹林和伏他仑）对禽流感和小鼠流感脑炎/脑病模型的影响。解热治疗对小鼠模型（IFV经神经传播模型）无影响，而对禽类脑炎/脑病（IFV血源性传播模型）有增强作用。伏他仑比阿司匹林更明显地夸大了病变（J Vet Med Sci,2004）。鞘内免疫将灭活的IFV或Aujezky病毒接种于兔和小鼠的鞘内（接种于脑脊液）或皮下。脑脊液抗体仅通过鞘内免疫提高。用灭活的Aujezky病毒鞘内免疫可以完全保护小鼠不因肌肉注射Aujezky病毒而出现临床症状、病理改变和死亡。结果表明，鞘内免疫对病毒侵袭部位经外周神经侵入中枢神经系统有一定的抑制作用。少

项目成果

The vagus nerve is one route of transneural invasion for intranasally inoculated influenza A virus in mice

• DOI: 10.1354/vp.41-2-101
• 发表时间: 2004-03-01
• 期刊: VETERINARY PATHOLOGY
• 影响因子: 2.4
• 作者: Matsuda, K;Park, CH;Umemura, T
• 通讯作者: Umemura, T

H.Tanaka: "Neurotropism of the 1997 Hong Kong H5N1 influenza virus in mice"Veterinary Microbiology. 95. 1-13 (2003)

H.Tanaka：“1997年香港H5N1流感病毒在小鼠体内的向神经性”兽医微生物学。

K.Matsuda: "The vagus nerve is one route of transneural invasion for intranasally inoculatad influenza A virus in mice"Veterinary Pathology. 41(in press). (2004)

K.Matsuda：“迷走神经是小鼠鼻内接种甲型流感病毒经神经侵入的一种途径”《兽医病理学》。

Y.Sunden: "The effects of antipyretics on influenza virus encephalitis in mice and chicks"Journal of Veterinary Medical Science. 65. 1185-1188 (2003)

Y.Sunden：“退热药对小鼠和雏鸡流感病毒脑炎的影响”兽医医学杂志。

The effects of antipyretics on influenza virus encephalitis in mice and chicks.

• DOI: 10.1292/jvms.65.1185
• 发表时间: 2003-11
• 期刊: The Journal of veterinary medical science
• 作者: Y. Sunden;C. Park;K. Matsuda;Akiko Anagawa;Takashi Kimura;K. Ochiai;H. Kida;T. Umemura