Mediation of protection and recovery from experimental autoimmune encephalomyelitis by macrophages expressing the human voltage-gated sodium channel NaV1.5.

Multiple sclerosis (MS) is the most common nontraumatic cause of neurologic disability in young adults. Despite treatment, progressive tissue injury leads to accumulation of disability in many patients. Here, our goal was to develop an immune-mediated strategy to promote tissue repair and clinical recovery in an MS animal model.

Characterization of epithelial V-like antigen in human choroid plexus epithelial cells: potential role in CNS immune surveillance.

Prior work demonstrated that immune surveillance of the brain occurs primarily through the blood-cerebrospinal (CSF) fluid barrier rather than the blood-brain barrier endothelium. Recently, we identified epithelial V-like antigen (EVA), an immunoglobulin-like adhesion molecule, as a regulator of blood-CSF barrier integrity in a mouse model. Here we characterized EVA expression and function in human choroid plexus epithelial cells and analyzed its role in CD4 T lymphocyte adhesion.

Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A.

Voltage-gated sodium channels initiate electrical signaling in excitable cells such as muscle and neurons. They also are expressed in non-excitable cells such as macrophages and neoplastic cells. Previously, in macrophages, we demonstrated expression of SCN8A, the gene that encodes the channel NaV1.

Epithelial V-like antigen regulates permeability of the blood-CSF barrier.

Epithelial V-like antigen (EVA), a CD3-binding immunoglobulin-like protein, regulates embryonic thymic development. Here we demonstrate that EVA is expressed in choroid plexus from mature immune competent and lymphocyte-deficient (RAG-/-) mice. Choroid plexus epithelial cells from RAG-/- mice demonstrated reduced junctional integrity and enhanced permeability that was associated with decreased expression of E-cadherin and EVA mRNA as compared to wild-type mice.

Exacerbation of experimental autoimmune encephalomyelitis after withdrawal of phenytoin and carbamazepine.

Objective: In vitro observations and studies in murine experimental autoimmune encephalomyelitis (EAE) have shown protective effects of sodium channel blockers on central nervous system axons and improved clinical status when treatment is continued throughout the period of observation. Several clinical studies of sodium channel blockers are under way in patients with multiple sclerosis. Here we asked whether a protective effect would persist after withdrawal of a sodium channel blocker.

Expression of the voltage-gated sodium channel NaV1.5 in the macrophage late endosome regulates endosomal acidification.

Voltage-gated sodium channels expressed on the plasma membrane activate rapidly in response to changes in membrane potential in cells with excitable membranes such as muscle and neurons. Macrophages also require rapid signaling mechanisms as the first line of defense against invasion by microorganisms. In this study, our goal was to examine the role of intracellular voltage-gated sodium channels in macrophage function.

Characterization of a severe parenchymal phenotype of experimental autoimmune encephalomyelitis in (C57BL6xB10.PL)F1 mice.

We here describe a novel CD4 T cell adoptive transfer model of severe experimental autoimmune encephalomyelitis in (C57BL6xB10.PL)F1 mice. This FI cross developed severe disease characterized by extensive parenchymal spinal cord and brain periventricular white matter infiltrates.