Acta Tropica 98 (2006) 34–42 Characterization of the vascular changes in schistosomal portal (pipestem) fibrosis of mice Luciana M. Silva a , Ricardo Ribeiro-dos-Santos b , Milena B.P. Soares b , Zilton A. Andrade a,∗ a Laboratories of Experimental Pathology, Gon¸ calo Moniz Research Center/FIOCRUZ, Salvador, BA, Brazil b Tissue Engineering and Immunopharmacology, Gon¸ calo Moniz Research Center/FIOCRUZ, Salvador, BA, Brazil Received 25 August 2005; received in revised form 20 January 2006; accepted 20 January 2006 Available online 14 March 2006 Abstract Mice chronically infected with Schistosoma mansoni develop one of two anatomical forms of hepatic lesions: severe, periportal (pipestem) fibrosis or milder, isolated granulomas. The pathogenesis of periportal fibrosis is poorly understood. In this work we compared mice with either periportal fibrosis or isolated granulomas to identify specific markers of severe pathology. BALB/c or Swiss Webster mice were infected with 30 cercarie, once or six times, and liver biopsies were performed to classify the animals into two pathological groups 16 weeks later. Sixty percent of the animals sacrificed at 20 or 24 weeks had periportal fibrosis, 15–20% had isolated granulomas and the remainder had indeterminate pathology. There was no correlation between frequency of infections or egg burden (eggs/gliver) at 20 and 24 weeks post-infection and the development of periportal fibrosis. Livers with periportal fibrosis at 20 or 24 weeks of infection were characterized by larger areas of fibrotic tissue and greater vascularization compared to livers of mice with isolated granulomas. Plastic casts of the portal vein system showed marked changes in vascular structure in mice with periportal fibrosis, including collateral vessels sprouting from the main portal branches, amputation of the more delicate peripheral ramifications, and distortions of the medium and small branches. Vascular changes were not observed in mice with isolated granulomas. These results suggest that the interaction between schistosome eggs and portal vascular changes is of paramount importance in the development of pipestem fibrosis. © 2006 Elsevier B.V. All rights reserved. Keywords: Schistosoma mansoni; Periportal (pipestem) fibrosis; Periovular granulomas; Hepatic fibrosis 1. Introduction Despite the description a century ago of the char- acteristic “pipestem” lesion by Symmers (1904) the pathogenesis of schistosomal periportal fibrosis remains ∗ Corresponding author at: Laborat´ orio de Patologia Experimen- tal, Centro de Pesquisas Gonc¸alo Moniz/FIOCRUZ, Rua Waldemar Falc˜ ao, 121-Brotas, Salvador 40295-001, BA, Brazil. Tel.: +55 71 356 4320x266; fax: +55 71 356 2155. E-mail address: zilton@cpqgm.fiocruz.br (Z.A. Andrade). controversial. It is recognized that the lesion appears in heavily infected individuals and represents the mor- phological substratum of hepatosplenic schistosomiasis. However, not all heavily infected individuals living in an endemic area will necessarily develop hepatosplenic disease. The influence of several factors, such as host age and gender, genetic background, nutrition, immuno- logical status, and environmental factors have been dis- cussed (Prata, 1991), but evidence for their specific roles in pathogenesis is incomplete. There is no explanation for the finding that the majority of infected individuals 0001-706X/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.actatropica.2006.01.011