A preliminary neuropathological study of Japanese encephalitis in humans and a mouse model

Allison C. German, Khin Saw Aye Myint, Nguyen Thi Hoang Mai, Ian Pomeroy, Nguyen Hoan Phu, John Tzartos, Peter Winter, Jennifer Collett, Jeremy Farrar, Alan Barrett, Anja Kipar, Margaret M. Esiri, Tom Solomon

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


Japanese encephalitis virus is a mosquito-borne flavivirus that causes approximately 10 000 deaths annually in Asia. After a brief viraemia, the virus enters the central nervous system, but the means of crossing the blood-brain barrier is uncertain. We used routine histological staining, immunohistology and electron microscopy to examine brain material from four fatal human cases, and made comparisons with material from a mouse model. In human material there was oedema, perivascular inflammation, haemorrhage, microglial nodules and acellular necrotic foci, as has been described previously. In addition, there was new evidence suggestive of viral replication in the vascular endothelium, with endothelial cell damage; this included occasional viral antigen staining, uneven binding of the vascular endothelial cells to Ulex europaeus agglutinin I and ultrastructural changes. Viral antigen was also found in neurons. There was an active astrocytic response, as shown by glial fibrillary acidic protein staining, and activation of microglial cells was demonstrated by an increase in major histocompatibility complex class II expression. Similar inflammatory infiltrates and a microglial reaction were observed in mouse brain tissue. In addition, β-amyloid precursor protein staining indicated impaired axonal transport. Whether these findings are caused by viral replication in the vascular endothelium or the immune response merits further investigation.

Original languageEnglish (US)
Pages (from-to)1135-1145
Number of pages11
JournalTransactions of the Royal Society of Tropical Medicine and Hygiene
Issue number12
StatePublished - Dec 2006


  • Arbovirus
  • Blood brain barrier
  • Japanese encephalitis
  • Zoonosis

ASJC Scopus subject areas

  • Parasitology
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases


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