The role of TNF in neuroinflammation

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

17-2786

Abstract. Human immunodeficiency virus (HIV)infection is usually followed by opportunistic infections, especially in the full-blown acquired immunodeficiency syndrome (AIDS). This study details the histopathological changes of different organs in relation to HIV infection, with particular emphasis on the opportunistic infections. Various organs from seventeen HIV-infected patients were collected by necropsy and analyzed for histopathological changes. The major histopathological changes included cytomegalovirus infection, cryptococcosis, penicilliosis, bacterial pneumonia, cryptosporidiosis, pneumocystosis, candidiasis, tuberculosis, granulomatosis of unknown etiology, early cirrhosis and chronic active hepatitis. General organ changes from seventeen cases of HIV-infected patients were described and discussed

A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI

Human and murine cerebral malaria are associated with elevated levels of cytokines in the brain and adherence of platelets to the microvasculature. Here we demonstrated that the accumulation of platelets in the brain microvasculature can be detected with MRI, using what we believe to be a novel contrast agent, at a time when the pathology is undetectable by conventional MRI. Ligand-induced binding sites (LIBS) on activated platelet glycoprotein IIb/IIIa receptors were detected in the brains of malaria-infected mice 6 days after inoculation with Plasmodium berghei using microparticles of iron oxide (MPIOs) conjugated to a single-chain antibody specific for the LIBS (LIBS-MPIO). No binding of the LIBS-MPIO contrast agent was detected in uninfected animals. A combination of LIBS-MPIO MRI, confocal microscopy, and transmission electron microscopy revealed that the proinflammatory cytokine TNF-α, but not IL-1β or lymphotoxin-α (LT-α), induced adherence of platelets to cerebrovascular endothelium. Peak platelet adhesion was found 12 h after TNF-α injection and was readily detected with LIBS-MPIO contrast-enhanced MRI. Temporal studies revealed that the level of MPIO-induced contrast was proportional to the number of platelets bound. Thus, the LIBS-MPIO contrast agent enabled noninvasive detection of otherwise undetectable cerebral pathology by in vivo MRI before the appearance of clinical disease, highlighting the potential of targeted contrast agents for diagnostic, mechanistic, and therapeutic studies