158 Chapter 7 Table 1. Astrocyte involvement in white matter CNS diseases Disease Pathology Detrimental impact on astrocytes Beneficial impact on astrocytes Ref Inflammatory MS Inflammation, myelin loss, neurodegeneration, astrogliosis, astrocyte damage. BBB damage, impaired signal transduction and glutamate clearance. Reduced OPC proliferation Gliosis may aid remyelination and regenerate integrity of BBB, aid remyelination and provide trophic support 5,23-26 NMO Inflammation, myelin loss in optic nerve and spinal cord. Reduction in AQP4 and GFAP. Decreased EAAT2. Impaired water and ion homeostasis, impaired glutamate clearance Stimulation of remyelination, trophic support 24, 27-29 ADEM Widespread CNS inflammation associated with infection. Dependent on infectious agent Infection may trigger protective response via TLR-dependent mechanism 30 AHL Perivascular demyelination, inflammation, oedema, haemorrhages. Hyperreactive astrocytes. Swelling of protoplasmic and fibrous astrocyte end-feet, beading consistent with degeneration. Demyelination is secondary to astrocyte injury indicating a beneficial effect of astrocytes in early disease 31 Infectious PML Cytolytic JC virus induces oligodendrocytes death and focal myelin loss. Abnormal astrocytes with inclusion bodies. Astrocytes aid the spread of JC virus to neighbouring oligodendrocytes Unknown 32-34 SSPE Viral inclusion bodies in neurons, neuronal damage and loss. Virion inclusion in some astrocytes. Infection of (perivascular) astrocytes may aid spread of virus Reactive gliosis in longstanding disease may be beneficial 35,36 Congenital CMV Encephalitis, microglial activation. CMV infection of astrocytes induces TGF-beta known to enhance productive infection. Infection of foetal astrocytes alters uptake and metabolism of glutamate Unknown 37,38
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