TLR3 agonism re-establishes CNS immune competence during 4-integrin deficiency.

Objective: Natalizumab blocks 4-integrin-mediated leukocyte migration into the central nervous system (CNS). It diminishes disease activity in multiple sclerosis (MS), but carries a high risk of progressive multifocal encephalopathy (PML), an opportunistic infection with JV virus that may be prompted by diminished CNS immune surveillance. The initial host response to viral infections entails the synthesis of type I interferons (IFN) upon engagement of TLR3 receptors.

Immune surveillance of the central nervous system in multiple sclerosis--relevance for therapy and experimental models.

Treatment of central nervous system (CNS) autoimmune disorders frequently involves the reduction, or depletion of immune-competent cells. Alternatively, immune cells are being sequestered away from the target organ by interfering with their movement from secondary lymphoid organs, or their migration into tissues. These therapeutic strategies have been successful in multiple sclerosis (MS), the most prevalent autoimmune inflammatory disorder of the CNS.

Testing effects of glatiramer acetate and fingolimod in an infectious model of CNS immune surveillance.

Immune surveillance of the CNS is critical for preventing infections; however, there is no accepted experimental model to assess the risk of infection when utilizing disease-modifying agents. We tested two approved agents for patients with multiple sclerosis (MS), glatiramer acetate and fingolimod, in an experimental model of CNS immune surveillance. C57BL/6 mice were infected with the ME49 strain of the neuroinvasive parasite Toxoplasma gondii (T.

Direct and consensual murine pupillary reflex metrics: establishing normative values.

Pupillometry is a non-invasive technique, based on well-established neurophysiologic principles, that can be utilized to objectively characterize pathophysiologic demyelinating and neurodegenerative changes involving the pupillary reflex pathway. In animal models of human disorders, pupillometry derived reflex metrics could potentially be used to longitudinally monitor disease activity and responses to pharmacotherapies. These investigations would have important implications for translational initiatives focused on the identification and application of novel neuroprotective and restorative treatments for human diseases such as multiple sclerosis.