Plasmodium berghei NK65 induces cerebral leukocyte recruitment in vivo: An intravital microscopic study

• Published in: Acta tropica Vol. 120; no. 1-2; pp. 31 - 39
• Main Authors: Lacerda-Queiroz, Norinne, Lima, Onésia Cristina Oliveira, Carneiro, Cláudia Martins, Vilela, Márcia Carvalho, Teixeira, Antônio Lúcio, Carvalho, Andrea Teixeira, Araújo, Márcio Sobreira Silva, Martins-Filho, Olindo Assis, Braga, Érika Martins, Carvalho-Tavares, Juliana
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.10.2011; Elsevier
• Subjects: adhesion; Animals; Biological and medical sciences; blood-brain barrier; Blood-Brain Barrier - immunology; Blood-Brain Barrier - metabolism; brain; Brain - blood supply; Brain - immunology; Capillary Permeability - physiology; Cell Adhesion - immunology; Cerebral inflammation; Chemokines; Chemokines - immunology; Chemokines - metabolism; Disease Models, Animal; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; Experimental malaria; Female; General aspects; histopathology; Human protozoal diseases; immune response; Immunohistochemistry - methods; Infectious diseases; inflammation; Inflammation - immunology; Intravital microscopy; Leukocytes - immunology; Leukocytes - metabolism; Malaria; Malaria - immunology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microcirculation; Microscopy, Fluorescence; morbidity; mortality; Mycobacterium; parasites; Parasitic diseases; parenchyma; pathogens; permeability; Plasmodium berghei; Plasmodium berghei - immunology; Plasmodium berghei NK65; Protozoal diseases; Species Specificity; tuberculosis; tumor necrosis factor-alpha; Intravital microscopy; Microcirculation; Plasmodium berghei NK65; Experimental malaria; Cerebral inflammation; Chemokines; Protozoa; Apicomplexa; Protozoal disease; Malaria; Leukocyte; Inflammation; Parasitosis; Encephalon; Recruitment; Infection; Chemokine; In vivo; Plasmodium berghei; Microscopy; Tropical medicine
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/j.actatropica.2011.04.020

Cerebral inflammation (leukocyte recruitment, blood brain barrier permeability and chemokine production) was clearly evident in C57BL/6 and BALB/c mice inoculated with Plasmodium berghei NK65. [Display omitted] ► We examine cerebral inflammatory changes after Plasmodium berghei NK65 infection. ► Pro-inflammatory cytokines and chemokines increase in both strains infected mice. ► Leukocyte recruitment and vascular permeability increase following infection. ► P. berghei NK65 infection induce CNS inflammation without neurological injury signs. Malaria is second only to tuberculosis as the leading cause of morbidity and mortality as a consequence of a single infectious agent. Much of the pathology of malaria arises from the inappropriate or excessive immune response mounted by the host in an attempt to eliminate the parasite. We here report the inflammatory changes observed in the cerebral microvasculature of C57BL/6 and BALB/c mice that had been inoculated with Plasmodium berghei NK65, a lethal strain of rodent malaria. Although no neurological signs were observed in experimentally infected mice, inflammation of the cerebral microvasculature was clearly evident. Histopathological analysis demonstrated that alterations in cerebral tissue were more intense in infected C57Bl/6 mice than in infected BALB/c animals. Intravital microscopic examination of the cerebral microvasculature revealed increased leukocyte rolling and adhesion in pial venules of infected mice compared with non-infected animals. The extravasation of Evans blue dye into the cerebral parenchyma was also elevated in infected mice in comparison with their non-infected counterparts. Additionally, protein levels of TNF-α, MIG/CXCL9, MCP-1/CCL2, MIP-1α/CCL3 and RANTES/CCL5 were up-regulated in brain samples derived from infected C57Bl/6 mice. Taken together, the data reported here illustrate the complex strain-dependent relationships between leukocyte recruitment, blood brain barrier permeability and chemokine production.