Copyright (c) 2009 Thomas Jefferson University All rights reserved. http://jdc.jefferson.edu Recent documents in Jefferson Digital Commons en-us Fri, 06 Nov 2009 05:42:49 PST 3600 http://jdc.jefferson.edu/fmfp/18 http://jdc.jefferson.edu/fmfp/18 Thu, 05 Nov 2009 10:45:31 PST The emotional investment required to construct a caring doctor-patient relationship can be justified on humane grounds. Can it also be justified as a direct physiologic intervention? Two lines of evidence point in this direction. People in an empathic relationship exhibit a correlation of indicators of autonomic activity. This occurs between speakers and responsive listeners, members of a coherent group, and bonded pairs of higher social animals. Furthermore, the experience of feeling cared about in a relationship reduces the secretion of stress hormones and shifts the neuroendocrine system toward homeostasis. Because the social engagement of emotions is simultaneously the social engagement of the physiologic substrate of those emotions, the process has been labeled sociophysiology. This process can influence the health of both parties in the doctor-patient relationship, and may be relevant to third parties. Herbert M. Adler http://jdc.jefferson.edu/hpn/vol22/iss3/14 http://jdc.jefferson.edu/hpn/vol22/iss3/14 Thu, 05 Nov 2009 10:43:13 PST http://jdc.jefferson.edu/neurologyfp/27 http://jdc.jefferson.edu/neurologyfp/27 Fri, 30 Oct 2009 13:04:28 PDT Optic neuritis (ON), an inflammatory demyelinating optic nerve disease, occurs in multiple sclerosis (MS). Pathological mechanisms and potential treatments for ON have been studied via experimental autoimmune MS models. However, evidence suggests that virus-induced inflammation is a likely etiology triggering MS and ON; experimental virus-induced ON models are therefore required. We demonstrate that MHV-A59, a mouse hepatitis virus (MHV) strain that causes brain and spinal cord inflammation and demyelination, induces ON by promoting mixed inflammatory cell infiltration. In contrast, MHV-2, a nondemyelinating MHV strain, does not induce ON. Results reveal a reproducible virus-induced ON model important for the evaluation of novel therapies. Kenneth S. Shindler Animals Antigens, CD11b Brain Demyelinating Diseases Fluorescent Antibody Technique, Indirect Immunohistochemistry Mice Mice, Inbred C57BL Murine hepatitis virus Optic Neuritis Spinal Cord http://jdc.jefferson.edu/neurologyfp/26 http://jdc.jefferson.edu/neurologyfp/26 Fri, 30 Oct 2009 12:55:05 PDT BACKGROUND: Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood. METHODS: EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ hybridization, and immunohistochemistry. Cell-type specific expression was examined in isolated astrocytic and microglial cell cultures. Cytokine and chemokine production was measured in IL-17A treated cultures to evaluate the functional status of IL-17RA. RESULTS: Here we report increased IL-17RA expression in the CNS of mice with EAE, and constitutive expression of functional IL-17RA in mouse CNS tissue. Specifically, astrocytes and microglia express IL-17RA in vitro, and IL-17A treatment induces biological responses in these cells, including significant upregulation of MCP-1, MCP-5, MIP-2 and KC chemokine secretion. Exogenous IL-17A does not significantly alter the expression of IL-17RA in glial cells, suggesting that upregulation of chemokines by glial cells is due to IL-17A signaling through constitutively expressed IL-17RA. CONCLUSION: IL-17RA expression is significantly increased in the CNS of mice with EAE compared to healthy mice, suggesting that IL-17RA signaling in glial cells can play an important role in autoimmune inflammation of the CNS and may be a potential pathway to target for therapeutic interventions. Jayasri Das Sarma Animals Animals, Newborn Antigens, CD11b Cells, Cultured Central Nervous System Chemokines Disease Models, Animal Encephalomyelitis, Autoimmune, Experimental Flow Cytometry Gene Expression Regulation Glial Fibrillary Acidic Protein Interleukin-17 Male Mice Mice, Inbred C57BL Myelin-Associated Glycoprotein Neuroglia Protein Array Analysis RNA, Messenger Receptors, Interleukin-17 Time Factors http://jdc.jefferson.edu/neurologyfp/25 http://jdc.jefferson.edu/neurologyfp/25 Fri, 30 Oct 2009 12:45:47 PDT Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Recent studies have demonstrated that significant axonal injury also occurs in MS patients and correlates with neurological dysfunction, but it is not known whether this neuronal damage is a primary disease process, or occurs only secondary to demyelination. In the current studies, neurotropic strains of mouse hepatitis virus (MHV) that induce meningitis, encephalitis, and demyelination in the CNS, an animal model of MS, were used to evaluate mechanisms of axonal injury. The pathogenic properties of genetically engineered isogenic spike protein recombinant demyelinating and nondemyelinating strains of MHV were compared. Studies demonstrate that a demyelinating strain of MHV causes concomitant axonal loss and macrophage-mediated demyelination. The mechanism of axonal loss and demyelination in MHV infection is dependent on successful transport of virus from gray matter to white matter using the MHV host attachment spike glycoprotein. Our data show that axonal loss and demyelination can be independent direct viral cytopathic events, and suggest that similar direct axonal damage may occur in MS. These results have important implications for the design of neuroprotective strategies for CNS demyelinating disease, and our model identifies the spike protein as a therapeutic target to prevent axonal transport of neurotropic viruses. Jayasri Das Sarma Animals Axons Cells, Cultured Disease Models, Animal Inflammation Mediators Mice Mice, Inbred C57BL Multiple Sclerosis Murine hepatitis virus Myelin Sheath Nerve Degeneration http://jdc.jefferson.edu/pacbfp/31 http://jdc.jefferson.edu/pacbfp/31 Thu, 29 Oct 2009 10:42:45 PDT Some strains of mouse hepatitis virus (MHV) can induce chronic inflammatory demyelination in mice that mimics certain pathological features of multiple sclerosis. We have examined neural cell tropism of demyelinating and nondemyelinating strains of MHV in order to determine whether central nervous system (CNS) cell tropism plays a role in demyelination. Previous studies demonstrated that recombinant MHV strains, isogenic other than for the spike gene, differ in the extent of neurovirulence and the ability to induce demyelination. Here we demonstrate that these strains also differ in their abilities to infect a particular cell type(s) in the brain. Furthermore, there is a correlation between the differential localization of viral antigen in spinal cord gray matter and that in white matter during acute infection and the ability to induce demyelination later on. Viral antigen from demyelinating strains is detected initially in both gray and white matter, with subsequent localization to white matter of the spinal cord, whereas viral antigen localization of nondemyelinating strains is restricted mainly to gray matter. This observation suggests that the localization of viral antigen to white matter during the acute stage of infection is essential for the induction of chronic demyelination. Overall, these observations suggest that isogenic demyelinating and nondemyelinating strains of MHV, differing in the spike protein expressed, infect neurons and glial cells in different proportions and that differential tropism to a particular CNS cell type may play a significant role in mediating the onset and mechanisms of demyelination. Jayasri Das Sarma Animals Antigens, Viral Coronavirus Infections Gene Expression Regulation Male Mice Mice, Inbred C57BL Murine hepatitis virus Myelin Sheath Nervous System Diseases Spinal Cord Tropism http://jdc.jefferson.edu/hpn/vol22/iss3/13 http://jdc.jefferson.edu/hpn/vol22/iss3/13 Wed, 28 Oct 2009 07:28:44 PDT http://jdc.jefferson.edu/hpn/vol22/iss3/12 http://jdc.jefferson.edu/hpn/vol22/iss3/12 Wed, 28 Oct 2009 07:28:43 PDT http://jdc.jefferson.edu/hpn/vol22/iss3/11 http://jdc.jefferson.edu/hpn/vol22/iss3/11 Wed, 28 Oct 2009 07:28:42 PDT Joe Couto PharmD, MBA http://jdc.jefferson.edu/hpn/vol22/iss3/10 http://jdc.jefferson.edu/hpn/vol22/iss3/10 Wed, 28 Oct 2009 07:28:42 PDT