5, Table 1). In the liver, swollen hepatocytes and a greater number of Kupffer cells containing malarial pigment grains were observed at days 1 and 5, which were concentrated in centrilobular or portal areas ( Fig. 5, Table 1). Kidney damage, characterised by tubular necrosis, interstitial oedema, and inflammatory cell infiltration, was more severe at day 5 compared to day 1 ( Fig. 5, Table 1). In the model used Bortezomib cost in this study, which has frequently been employed for the induction of experimental cerebral malaria, mechanical and histological lung impairment associated with neutrophil

infiltration were observed 1 day following inoculation with Plasmodium berghei. this website Lung damage was accompanied by histological changes in distal organ tissues, namely the brain (which exhibited glial cell swelling, capillary congestion, increased number

of microglial cells), the heart (interstitial oedema, capillary congestion, and increased number of mononuclear cells), the liver (Kupffer cell injury), and the kidneys (tubular necrosis and interstitial oedema). These changes in lung mechanics and histology had reduced by day 5. However, there was progressive heart and kidney damage associated with an increase in pro-inflammatory cytokines. Moreover, mice inoculated with P. berghei-infected erythrocytes demonstrated greater mortality beginning 6 days post-infection, in accordance with previous studies ( Clemmer et al., 2011, ID-8 Martins et al., 2012 and Souza et al., 2012). Epidemiological studies suggest that 5% of patients with uncomplicated malaria and 20–30% of patients with severe malaria develop ALI (Mohan et al., 2008); nevertheless, the development of ALI during malaria is poorly understood. Indeed,

histopathological observation of human organs is limited to post-mortem analysis of fatal cases of severe malaria, and the sequence of events leading to the onset of cerebral malaria has not been described. Neuropathological syndromes have previously been described in susceptible strains of inbred mice infected with P. berghei ( Rest, 1982 and Curfs et al., 1993), but lung injury during experimental severe malaria has only been suggested and was only thought to occur during the late stages of P. berghei infection ( Epiphanio et al., 2010, Van den Steen et al., 2010 and Hee et al., 2011). Thus, we examined the development of ALI at early and late time points after P. berghei infection focusing on the following parameters: lung histology, inflammatory response, changes in the alveolar capillary barrier (oedema), physiological dysfunctions as well as the correlation of ALI with cytokine production and distal organ damage.