levels and neuronal death. They can also impair the transport of glutamate in astrocytes.
Pathological studies of MS lesions suggest an important role of macrophages and microglia in MS demyelination. Active or recent plaques have areas of myelin degradation, infiltration by inflammatory cells, and collections of lipid-containing macrophages that may stain for myelin proteins such as myelin basic protein. In chronic plaques, macrophage-like cells remain lipid-laden but no longer express immunor-eactive myelin proteins. Some of these macrophages represent phagocytic microglia and some may be of hematogenous origin. MS lesions are frequently localized in perivascular regions and contain not only demyelinated axons and microglia but also lymphocytes and plasma cells. The presence of MHC II molecules in macrophages and microglia in MS lesions indicates that microglia are activated and can exert phagocytosis and antigen presentation functions. They also express Fc receptors and have an increased number of chemotactic receptors, including C5a and IL8.
Figure 5 Neuropathological hallmarks of HIV infection. (A) Multinucleated giant cells are considered to be histological lesions directly attributed to HIV infection. (B) Microglial nodules, frequently observed in the brain of HIV-infected patients, are associated with opportunistic cerebral infections.
3. Alzheimer's Disease
Alzheimer's disease is a degenerative disorder characterized by memory loss eventually leading to dementia. Pathologically, AD is characterized by the presence of insoluble structures or depositions in cortical regions of the brain, namely b-amyloid (Ab)-containing extracellular plaques and intraneuronal neurofibrillary tangles. The presence of large numbers of activated microglia and reactive astrocytes in brain tissue from AD patients has been interpreted as a secondary event. However, evidence suggests a significant role of these cells in the progression of the disease. Microglia cluster around Ab-containing senile plaques with markedly enhanced MHC II protein expression on microglial cells associated with areas of degenerative pathology. Cytokines such as IL-1, IL-6, and TNF-a also have increased expression in microglia in the vicinity of senile plaques. These cytokines can potentially coordinate the majority of inflammatory changes found in AD brain tissue; however, a classic immune response as defined by the involvement of T cells or immunoglobulins does not appear to occur. The presence of microglia in the vicinity of amyloid plaques suggests a function in phagocytosis and plaque removal. Microglia can also uptake and degrade Ab with a limited rate. In culture studies, synthetic Ab not only recruits and activates microglia but also induces the secretion of cytotoxic products by these cells. Thus, rather than being protective, the activation of micro-glial cells may result in further neurotoxicity. Moreover, microglia can synthesize and secrete Ab. Therefore, the stimulus of Ab production may be Ab.
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