Tumor necrosis factor alpha is reparative via TNFR2 [corrected] in the hippocampus and via TNFR1 [corrected] in the striatum after virus-induced encephalitis.

Differentiating between injurious and reparative factors facilitates appropriate therapeutic intervention. We evaluated the role of tumor necrosis factor alpha (TNFalpha) in parenchymal brain pathology resolution following virus-induced encephalitis from a picornavirus, Theiler's murine encephalomyelitis virus (TMEV). We infected the following animals with TMEV for 7 to 270 days: B6/129 TNF(-/-) mice (without TNFalpha expression), B6/129 TNFR1(-/-) mice (without TNFalpha receptor 1 expression), and B6/129 TNFR2(-/-) mice (without TNFalpha receptor 2 expression).

A human antibody that promotes remyelination enters the CNS and decreases lesion load as detected by T2-weighted spinal cord MRI in a virus-induced murine model of MS.

The human monoclonal antibody rHIgM22 enhances remyelination following spinal cord demyelination in a virus-induced murine model of multiple sclerosis. Using three-dimensional T2-weighted in vivo spinal cord magnetic resonance imaging (MRI), we have therefore assessed the extent of spinal cord demyelination, before and after 5 weeks of treatment with rHIgM22, to determine whether antibody enhanced remyelination can be detected by MRI. A significant decrease was seen in T2 high signal lesion volume following antibody treatment.

Dynamics of MRI lesion development in an animal model of viral-induced acute progressive CNS demyelination.

Theiler's murine encephalitis virus (TMEV) infection in mice is an established model of CNS demyelinating diseases. The aim of the study was to determine the chronological pattern of lesion development in this model of monophasic fulminant demyelinating disease. We followed six highly susceptible interferon-gamma receptor knockout mice with serial in vivo brain magnetic resonance imaging (MRI) studies to determine changes in overall T2 lesion load and gadolinium enhancement.

Disappearing "T1 black holes" in an animal model of multiple sclerosis.

Brain MRI in multiple sclerosis (MS) frequently shows areas of hypointensity in the white matter on T1 weighted sequences ("T1 black holes"). These areas are thought to be consistent with irreversible axonal loss. In this study T1 black holes were characterized in Theiler's Murine Encephalitis Virus infection, an established model of demyelinating diseases in mice.

In vivo magnetic resonance imaging of immune cells in the central nervous system with superparamagnetic antibodies.

We developed a novel MRI technique to image immune cell location and homing in vivo to the central nervous system (CNS). Superparamagnetic antibodies specific for cell surface markers allowed imaging of CD4+ T cells, CD8+ T cells, and Mac1+ cells in the CNS of mice infected with Theiler's murine encephalomyelitis virus (TMEV) and in mice with experimental autoimmune encephalomyelitis (EAE). Superparamagnetic antibodies have excellent T2, T2*, and good T1 relaxation properties, which makes them ideal MRI contrast materials.

Gamma interferon is critical for neuronal viral clearance and protection in a susceptible mouse strain following early intracranial Theiler's murine encephalomyelitis virus infection.

We evaluated the role of gamma interferon (IFN-gamma) in protecting neurons from virus-induced injury following central nervous system infection. IFN-gamma(-/-) and IFN-gamma(+/+) mice of the resistant major histocompatibility complex (MHC) H-2(b) haplotype and intracerebrally infected with Theiler's murine encephalomyelitis virus (TMEV) cleared virus infection from anterior horn cell neurons. IFN-gamma(+/+) H-2(b) mice also cleared virus from the spinal cord white matter, whereas IFN-gamma(-/-) H-2(b) mice developed viral persistence in glial cells of the white matter and exhibited associated spinal cord demyelination.

Magnetic resonance imaging of immune cells in inflammation of central nervous system.

Aim: To develop a novel, magnetic resonance-based method for in vivo cell localization in the central nervous system (CNS) of the animals without sacrificing them.

Methods: Cells were labeled in vivo by intravenous injection of cell marker-specific antibodies covalently bound to ultrasmall superparamagnetic iron oxide particles (USPIO). This enabled the visualization of specific cell types by magnetic resonance microscopy (MRM).

Direct comparison of demyelinating disease induced by the Daniel's strain and BeAn strain of Theiler's murine encephalomyelitis virus.

We compared CNS disease following intracerebral injection of SJL mice with Daniel's (DA) and BeAn 8386 (BeAn) strains of Theiler's murine encephalomyelitis virus (TMEV). In tissue culture, DA was more virulent then BeAn. There was a higher incidence of demyelination in the spinal cords of SJL/J mice infected with DA as compared to BeAn.

Interleukin-6 protects anterior horn neurons from lethal virus-induced injury.

We evaluated the role of interleukin-6 (IL-6) in neuronal injury after CNS infection. IL-6-/- and IL-6+/+ mice of resistant major histocompatibility complex (MHC) H-2b haplotype intracerebrally infected with Theiler's virus cleared the infection normally without development of viral persistence, lethal neuronal infection, or late phase demyelination. In contrast, infection of IL-6-/- mice on a susceptible H-2q haplotype resulted in frequent deaths and severe neurologic deficits within 2 weeks of infection as compared with infected IL-6+/+ H-2q littermate controls.