Transactions of the Royal Society of Tropical Medicine and Hygiene (2006) xxx, xxx—xxx available at www.sciencedirect.com journal homepage: www.elsevierhealth.com/journals/trst A preliminary neuropathological study of Japanese encephalitis in humans and a mouse model Allison C. German a,b , Khin Saw Aye Myint c , Nguyen Thi Hoang Mai d , Ian Pomeroy e , Nguyen Hoan Phu d , John Tzartos e , Peter Winter a,b , Jennifer Collett a,b , Jeremy Farrar f , Alan Barrett g , Anja Kipar h , Margaret M. Esiri e , Tom Solomon a,b,* a Division of Medical Microbiology, University of Liverpool, Liverpool, UK b Division of Neurological Sciences, University of Liverpool, Liverpool, UK c Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand d Centre for Tropical Diseases, Cho Quan Hospital, Ho Chi Minh City, Viet Nam e Department of Neuropathology, Radcliffe Infirmary, Oxford, UK f University of Oxford—Wellcome Trust Clinical Research Unit, Ho Chi Minh City, Viet Nam g Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, and Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA h Department of Veterinary Pathology, University of Liverpool, Liverpool, UK Received 28 November 2005; received in revised form 20 February 2006; accepted 20 February 2006 KEYWORDS Arbovirus; Japanese encephalitis; Zoonosis; Blood brain barrier Summary Japanese encephalitis virus is a mosquito-borne flavivirus that causes approxi- mately 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 rou- tine 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 nod- ules 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 dam- age; 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 pro- tein staining, and activation of microglial cells was demonstrated by an increase in major ∗ Corresponding author. Viral Brain Infections Group, Divisions of Medical Microbiology and Neurological Sciences, 8th Floor Duncan Building, Liverpool L69 3GA, UK. Tel.: +44 151 706 4381; fax: +44 151 706 5805. E-mail address: tsolomon@liv.ac.uk (T. Solomon). 0035-9203/$ — see front matter © 2006 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.trstmh.2006.02.008 TRSTMH-463; No. of Pages 11