Journal of Neuroimmunology RSS feed: Current Issue. The Journal of Neuroimmunology affords a forum for the publication of works applying immunologic methodology to the furtherance of the neurological sciences. Studies on all branches of the neurosciences, particularly fundamental and applied neurobiology, neurology, neuropathology, neurochemistry, neurovirology, neuroendocrinology, neuromuscular research, neuropharmacology and psychology, which involve either immunologic methodology (e.g. immunocytochemistry) or fundamental immunology (e.g. antibody and lymphocyte assays), are considered for publication. Works pertaining to multiple sclerosis, AIDS, amyotrophic lateral sclerosis, Guillain Barré Syndrome, myasthenia gravis, and brain tumors form a major focus. The scope of the Journal is broad, covering both research and clinical problems of neuroscientific interest. A major aim of the Journal is to encourage the development of immunologic approaches to analyse in further depth the interactions and specific properties of nervous tissue elements during development and disease. http://www.jni-journal.com/?rss=yesElsevier Inc.en © 2011 Published by Elsevier Inc. All rights reserved. Journal of Neuroimmunology0165-57282391-228 October 2011 © 2011 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.jni-journal.com/article/PIIS0165572811002803/abstract?rss=yesEditorial Board10.1016/S0165-5728(11)00280-3Journal of Neuroimmunology 239, 1 (2011)2011-10-28Journal of Neuroimmunology2011-10-282391-2S0165-5728(11)X0010-3iiiiiihttp://www.jni-journal.com/article/PIIS016557281100227X/abstract?rss=yesAbstract: Toll-like receptors (TLR) are important innate immune proteins for the identification and clearance of invading pathogen. TLR signal through adaptor proteins, most commonly myeloid differentiation primary response gene 88 (MyD88). Inappropriate response of specific TLR has been implicated in certain autoimmune diseases, such as multiple sclerosis (MS). Activation of TLR2, TLR4, TLR7 and TLR9 plays a role in experimental allergic encephalomyelitis (EAE), a murine model of MS, while TLR3 activation protects from disease. Therefore, TLR-modulation could be an important adjuvant to current treatments. Here, we focus on TLR involved in EAE and MS pathogenesis highlighting specific components targeting TLR that might offer further therapeutic possibilities.Targeting Toll-like receptors: Emerging therapeutics for multiple sclerosis managementM. Gambuzza, N. Licata, E. Palella, D. Celi, V. Foti Cuzzola, D. Italiano, S. Marino, P. Bramanti10.1016/j.jneuroim.2011.08.010Journal of Neuroimmunology 239, 1 (2011)2011-09-05Journal of Neuroimmunology2011-09-052391-2S0165-5728(11)X0010-3Reviews112http://www.jni-journal.com/article/PIIS0165572811002293/abstract?rss=yesAbstract: The adaptive and innate arms of the immune system are the two pillars of host defense against environmental pathogens. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS which is considered to be autoimmune and is thought to result from breakdown in the usual checks and balances of the adaptive immune response. The major pathological outcome of the disease is “the MS plaque” a unique feature of CNS demyelination characterized by the destruction of oligodendrocytes with loss of myelin and underlying axons. The MS plaque is not seen in other inflammatory disorders of the CNS. The prevailing opinion suggests that MS is mediated by the activation of an adaptive immune response which targets neural antigens. Currently, the role of an innate immune in the development of the lesions in MS has remained unclear. We explore the potential cellular elements of the innate immune system and in particular glial cells, which are likely candidates in inducing the specific pathological picture that is evident in MS. Activated microglia and the release of molecules which are detrimental to oligodendrocyte have been suggested as mechanisms by which innate immunity causes demyelination in MS. However a microglia/macrophage centric model does not explain the specificity of lesion development in MS. We propose that activation pathways of receptors of the innate immune system present on oligodendrocytes and astrocytes rather than microglia are central to the pathogenesis of demyelination seen in MS.Role of glial cells in innate immunity and their role in CNS demyelinationSubramaniam Sriram10.1016/j.jneuroim.2011.08.012Journal of Neuroimmunology 239, 1 (2011)2011-09-12Journal of Neuroimmunology2011-09-122391-2S0165-5728(11)X0010-3Reviews1320http://www.jni-journal.com/article/PIIS0165572811002542/abstract?rss=yesAbstract: Virus-induced spinal cord damage results from a cytolytic effect on anterior horn cells or from predominantly cellular immune-mediated damage of long white matter tracts. Infection with the hepatitis virus group, most notably hepatitis C virus, has infrequently been associated with the occurrence of myelitis. The pathogenesis of hepatitis virus-associated myelitis has not been clarified: virus-induced autoimmunity (humoral or cell-mediated, possibly vasculitic) seems the most likely disease mechanism. Limited available information offers no evidence of direct hepatitis virus infection of the spinal cord. Virus neuropenetration may occur after virus-infected mononuclear cells penetrate the blood–brain barrier, but a true neurolytic effect has not been demonstrated. Attacks of acute myelitis usually respond favorably to immunomodulatory therapy. Antiviral therapy plays no confirmed role in the treatment of acute bouts of myelitis, but may limit the relapsing course of HCV-associated myelitis.Highlights: ► The maps generated indicate the existing problems in the physical environment. ► The maps generated functioning as a guide for urbanization. ► The occupations would be most appropriate if they occurred in the favorable areas. ► The multicriterial analysis implies infinite scenarios. ► The favorability maps represent a surface of suitability.Immune-mediated myelitis associated with Hepatitis virus infectionsJoerg-Patrick Stübgen10.1016/j.jneuroim.2011.09.001Journal of Neuroimmunology 239, 1 (2011)2011-09-26Journal of Neuroimmunology2011-09-262391-2S0165-5728(11)X0010-3Reviews2127http://www.jni-journal.com/article/PIIS0165572811002268/abstract?rss=yesAbstract: IL-6 is an important signaling molecule in the CNS. CNS neurons express IL-6 receptors and their signal transduction molecules, consistent with a role for IL-6 in neuronal physiology. Research indicates that IL-6 levels are low in the normal brain but can be significantly elevated in CNS injury and disease. Relatively little is known about how the elevated levels of IL-6 affect neurons. In the current study we show that under conditions of chronic exposure, IL-6 induces alterations in the level of protein expression in developing CNS cells. Such changes may play a role in the altered CNS function observed in CNS conditions associated with elevated levels of IL-6 in the CNS.Neuroadaptive changes in cerebellar neurons induced by chronic exposure to IL-6D.L. Gruol, A. Puro, C. Hao, P. Blakely, E. Janneke, K. Vo10.1016/j.jneuroim.2011.08.009Journal of Neuroimmunology 239, 1 (2011)2011-09-05Journal of Neuroimmunology2011-09-052391-2S0165-5728(11)X0010-3Research Papers2836http://www.jni-journal.com/article/PIIS0165572811002244/abstract?rss=yesAbstract: Immunological responses to protect against excessive inflammation can be regulated by the central nervous system through the cholinergic anti-inflammatory pathway wherein acetylcholine released from vagus nerves can inhibit inflammatory cytokines. Although a role for the α7 nicotinic acetylcholine receptor (α7 nAChR) in mediating this pathway has been suggested, pharmacological modulation of the pathway by selective agonists remains to be further elucidated. In this study, the role of α7 nAChRs in the regulation of TNF-α release was investigated using high affinity and selective α7 nAChR agonists in mouse peritoneal macrophage and human whole blood in vitro, and in mouse serum in vivo. In mouse peritoneal macrophages, LPS-induced TNF-α release in vitro was inhibited by a selective α7 nAChR agonist, A-833834 (5-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1H-indole), and that effect was attenuated by α7 nAChR antagonist methyllycaconitine. The inhibitory effect of A-833834 on LPS-induced TNF-α release was also observed in human whole blood in vitro. I.v. LPS-induced TNF-α release in mouse serum was attenuated following i.p. administration of A-833834. Similarly, i.v. LPS-induced TNF-α release in mouse serum was also attenuated following i.p. administration of A-585539, another α7 nAChR agonist with limited brain penetration, suggesting that these effects are mediated by peripheral α7 nAChRs. A-833834 was also efficacious in suppressing TNF-α release in mouse serum following oral administration in zymosan-induced peritonitis. These studies collectively demonstrate that selectively targeting α7 nAChRs could offer a novel therapeutic modality to treat acute and chronic inflammatory disease states.Role of α7 nicotinic acetylcholine receptors in regulating tumor necrosis factor-α (TNF-α) as revealed by subtype selective agonistsJinhe Li, Suzanne L. Mathieu, Richard Harris, Jianguo Ji, David J. Anderson, John Malysz, William H. Bunnelle, Jeffrey F. Waring, Kennan C. Marsh, Anwar Murtaza, Lisa M. Olson, Murali Gopalakrishnan10.1016/j.jneuroim.2011.08.007Journal of Neuroimmunology 239, 1 (2011)2011-09-12Journal of Neuroimmunology2011-09-122391-2S0165-5728(11)X0010-3Research Papers3743http://www.jni-journal.com/article/PIIS0165572811002232/abstract?rss=yesAbstract: Chronic social disruption stress (SDR) exacerbates acute and chronic phase Theiler's murine encephalomyelitis virus (TMEV) infection, a mouse model of multiple sclerosis. However, the precise mechanism by which this occurs remains unknown. The present study suggests that SDR exacerbates TMEV disease course by priming virus-induced neuroinflammation. It was demonstrated that IL-1β mRNA expression increases following acute SDR; however, IL-6 mRNA expression, but not IL-1β, is upregulated in response to chronic SDR. Furthermore, this study demonstrated SDR prior to infection increases infection related central IL-6 and IL-1β mRNA expression, and administration of IL-6 neutralizing antibody during SDR reverses this increase in neuroinflammation.Social disruption induced priming of CNS inflammatory response to Theiler's virus is dependent upon stress induced IL-6 releaseE.G. Vichaya, E.E. Young, M.A. Frazier, J.L. Cook, C.J. Welsh, M.W. Meagher10.1016/j.jneuroim.2011.08.006Journal of Neuroimmunology 239, 1 (2011)2011-10-17Journal of Neuroimmunology2011-10-172391-2S0165-5728(11)X0010-3Research Papers4452http://www.jni-journal.com/article/PIIS0165572811002281/abstract?rss=yesAbstract: Stimulating sensitized immune cells with a subsequent immune challenge results in potentiated pro-inflammatory responses translating into exacerbated sickness responses (i.e. fever, pain and lethargy). Both corticosterone (CORT) and laparotomy cause sensitization, leading to enhanced sickness-induced neuroinflammation or pain (respectively). However, it is unknown whether this sensitization affects all sickness behaviors and immune cell responses equally. We show that prior CORT and prior laparotomy potentiated LPS-induced fever but not lethargy. Prior CORT, like prior laparotomy, was able to potentiate sickness-induced pain. Release of nitric oxide (NO) from peritoneal macrophages stimulated ex vivo demonstrates that laparotomy, but not CORT sensitizes these cells.Prior laparotomy or corticosterone potentiates lipopolysaccharide-induced fever and sickness behaviorsLeah E. Hains, Lisa C. Loram, Frederick R. Taylor, Keith A. Strand, Julie L. Wieseler, Ruth M. Barrientos, Jennifer J. Young, Matthew G. Frank, Julia Sobesky, Thomas J. Martin, James C. Eisenach, Steven F. Maier, John D. Johnson, Monika Fleshner, Linda R. Watkins10.1016/j.jneuroim.2011.08.011Journal of Neuroimmunology 239, 1 (2011)2011-09-12Journal of Neuroimmunology2011-09-122391-2S0165-5728(11)X0010-3Research Papers5360http://www.jni-journal.com/article/PIIS0165572811002323/abstract?rss=yesAbstract: Dysfunction of the blood–brain barrier (BBB) and blood–spinal cord barrier (BSCB) is a primary characteristic of multiple sclerosis (MS). We evaluated the protective effects of fasudil, a selective ROCK inhibitor, in a model of experimental autoimmune encephalomyelitis (EAE) that was induced by guinea-pig spinal cord. In addition, we studied the effects of fasudil on BBB and BSCB permeability. We found that fasudil partly alleviated EAE-dependent damage by decreasing BBB and BSCB permeability. These results provide rationale for the development of selective inhibitors of Rho kinase as a novel therapy for MS.The effects of fasudil on the permeability of the rat blood–brain barrier and blood–spinal cord barrier following experimental autoimmune encephalomyelitisX.N. Huang, J. Fu, W.Z. Wang10.1016/j.jneuroim.2011.08.015Journal of Neuroimmunology 239, 1 (2011)2011-10-05Journal of Neuroimmunology2011-10-052391-2S0165-5728(11)X0010-3Research Papers6167http://www.jni-journal.com/article/PIIS0165572811002372/abstract?rss=yesAbstract: We tested the hypothesis that neonatal androgenization affects the efficacy of β-adrenoceptor (β-AR)-mediated fine tuning of thymopoiesis in adult female rats by modulating the thymic noradrenaline (NA) level and/or β-AR expression. In adult rats administered with 1000μg testosterone enanthate at postnatal day 2 a higher density of catecholamine (CA)-synthesizing thymic cells, including thymocytes, and a rise in their CA content was found. In addition, in these animals increased thymic noradrenergic nerve fiber fluorescence intensity, reflecting their increased CA content, was detected. These changes were followed by an increase in thymic NA concentration. The rise in thymic NA content in thymic nerve fibers and cells was associated with changes in the expression of mRNA for enzymes controling pivotal steps in NA biosynthesis (tyrosine hydroxylase, dopamine-β-hydroxylase) and inactivation (monoamine oxidase). In contrast, the thymic level of β2-AR mRNA on a per cell basis and the receptor surface density on thymocytes was reduced in testosterone-treated (TT) rats. As a consequence, 14-day-long treatment with propranolol, a β-AR blocker, was ineffective in modulating T-cell differentiation/maturation in TT rats. In conclusion, the study indicates the importance of the neonatal sex steroid milieu for shaping the immunomodulatory capacity of the thymic NA/β-AR signaling system in adult rats.Neonatal androgenization affects the efficiency of β-adrenoceptor-mediated modulation of thymopoiesisKatarina Radojević, Duško Kosec, Milica Perišić, Ivan Pilipović, Biljana Vidić-Danković, Gordana Leposavić10.1016/j.jneuroim.2011.08.020Journal of Neuroimmunology 239, 1 (2011)2011-09-23Journal of Neuroimmunology2011-09-232391-2S0165-5728(11)X0010-3Research Papers6879http://www.jni-journal.com/article/PIIS0165572811002360/abstract?rss=yesAbstract: In this study, we assessed B cell subsets, including Bregs, during stable and active disease in relapsing remitting multiple sclerosis (RRMS) patients and related B cell subsets to vitamin D status. We report that RRMS patients have a decreased percentage of both memory B cells and Bregs compared to healthy controls. During a relapse, the reduction in Bregs involved in particular naïve Bregs. We found no correlation between vitamin D status and B cell subsets. An effect of vitamin D on Bregs cannot be ruled out, since it might be the function that is interfered with instead of relative numbers.Reduction in IL-10 producing B cells (Breg) in multiple sclerosis is accompanied by a reduced naïve/memory Breg ratio during a relapse but not in remissionStephanie Knippenberg, Evelyn Peelen, Joost Smolders, Mariëlle Thewissen, Paul Menheere, Jan Willem Cohen Tervaert, Raymond Hupperts, Jan Damoiseaux10.1016/j.jneuroim.2011.08.019Journal of Neuroimmunology 239, 1 (2011)2011-09-22Journal of Neuroimmunology2011-09-222391-2S0165-5728(11)X0010-3Clinical Neuroimmunology8086http://www.jni-journal.com/article/PIIS0165572811002335/abstract?rss=yesAbstract: LM1 is localized in human peripheral nerve myelin. Antibodies to ganglioside complexes (GSCs) have been reported in Guillain–Barré syndrome (GBS). We investigated IgG antibodies to LM1 and two GSCs (GM1 and LMI, or GD1b and LM1) in the sera of each 40 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and GBS, using ELISA. We detected anti-LM1 antibody in five with GBS and seven with CIDP; anti-GM1/LM1 antibody in three with GBS and one with CIDP; and anti-GD1b/LM1 antibody in two with CIDP. Antibodies to LM1 and LM1-containing GSCs may be among the targets for autoimmunity in GBS and CIDP.Antibodies to LM1 and LM1-containing ganglioside complexes in Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathyMotoi Kuwahara, Seiko Suzuki, Kazuo Takada, Susumu Kusunoki10.1016/j.jneuroim.2011.08.016Journal of Neuroimmunology 239, 1 (2011)2011-09-14Journal of Neuroimmunology2011-09-142391-2S0165-5728(11)X0010-3Clinical Neuroimmunology8790http://www.jni-journal.com/article/PIIS0165572811002256/abstract?rss=yesAbstract: No disease-specific neuronal antibodies have so far been defined in neuro-Behçet's disease (NBD). Immunohistochemistry and immunocytochemistry studies showed antibodies to hippocampal and cerebellar molecular layers and the surface antigens of cultured hippocampal neurons in sera and/or cerebrospinal fluids (CSF) of 13 of 20 NBD and 6 of 20 BD patients but not in multiple sclerosis or headache controls. Screening with a protein macroarray led to identification of stress-induced-phosphoprotein-1 (STIP-1) as an antigenic target. High-titer STIP-1-antibodies were detected in 6 NBD patients' sera but not in controls. These results suggest that neuronal antibodies could be useful as diagnostic biomarkers in NBD.Anti-neuronal and stress-induced-phosphoprotein 1 antibodies in neuro-Behçet's diseaseBurçak Vural, Elif Uğurel, Erdem Tüzün, Murat Kürtüncü, Luigi Zuliani, Filiz Çavuş, Sema İçöz, Ece Erdağ, Ahmet Gül, Ali O. Güre, Angela Vincent, Uğur Özbek, Mefkure Eraksoy, Gülşen Akman-Demir10.1016/j.jneuroim.2011.08.008Journal of Neuroimmunology 239, 1 (2011)2011-08-29Journal of Neuroimmunology2011-08-292391-2S0165-5728(11)X0010-3Clinical Neuroimmunology9197http://www.jni-journal.com/article/PIIS0165572811002359/abstract?rss=yesAbstract: Role of mannose binding lectin (MBL) complement activation pathway, an arm of innate immunity in multiple sclerosis (MS) was evaluated by analyzing the expression of MBL, MBL-associated serine protease-2 (MASP-2), and functional MBL/MASP-2 mediated C4 cleavage (fMBL) in 87 plasma and cerebrospinal fluid (CSF) samples from MS patients and non-MS controls. Median fMBL and MASP-2 plasma levels were higher in MS vs. non-MS cases. These associations remained in an analysis of subtypes of MS disease. These findings suggest a potential activation of MBL complement pathway in MS that may possibly alter the risk or progression of MS disease.Mannose binding lectin mediated complement pathway in multiple sclerosisJanet Y. Kwok, Florin Vaida, Ryan M. Augst, Denise Y. Yu, Kumud K. Singh10.1016/j.jneuroim.2011.08.018Journal of Neuroimmunology 239, 1 (2011)2011-09-12Journal of Neuroimmunology2011-09-122391-2S0165-5728(11)X0010-3Short Communications98100http://www.jni-journal.com/article/PIIS0165572811002219/abstract?rss=yesAbstract: Recent studies have revealed an association between interleukin 28B (IL28B) and response to IFN-alpha treatment in hepatitis C patients. Here we investigated the influence of IL28B polymorphisms in the response to interferon-beta (IFNβ) in multiple sclerosis (MS) patients. We genotyped two SNPs of the IL28B gene (rs8099917 and rs12979860) in 588 MS patients classified into responders (n=281) and non-responders (n=307) to IFNβ. Combined analysis of the study cohorts showed no significant associations between SNPs rs8099917 and rs12979860 and the response to treatment. These findings do not support a role of IL28B polymorphisms in the response to IFNβ in MS patients.IL28B polymorphisms are not associated with the response to interferon-beta in multiple sclerosisS. Malhotra, C. Morcillo-Suárez, D. Brassat, R. Goertsches, J. Lechner-Scott, E. Urcelay, O. Fernández, J. Drulovic, A. García-Merino, F. Martinelli Boneschi, A. Chan, K. Vandenbroeck, A. Navarro, M.F. Bustamante, J. Río, D.A. Akkad, G. Giacalone, A.J. Sánchez, L. Leyva, R. Alvarez-Lafuente, U.K. Zettl, J. Oksenberg, X. Montalban, M. Comabella10.1016/j.jneuroim.2011.08.004Journal of Neuroimmunology 239, 1 (2011)2011-09-02Journal of Neuroimmunology2011-09-022391-2S0165-5728(11)X0010-3Short Communications101104http://www.jni-journal.com/article/PIIS0165572811002311/abstract?rss=yesBehçet's disease (BD) is a vasculitis characterized by hallmark lesions of oral and genital ulcers (). Involvement of parenchymal central nervous system (neuro-BD) is a serious complication commonly characterized by brainstem and/or basal ganglia lesions (). To date, the treatment of neuro-BD remains largely empirical, and may not adequately control the disease (). Given the well-recognized role played by tumor necrosis factor-α (TNFα) in the pathogenesis of active BD (), infliximab (a monoclonal antibody that binds to and neutralizes the activity of TNFα) has been adopted with favorable results in patients resistant to conventional immunosuppressive therapies and in a small placebo controlled study (). A review of published cases reveals that the follow-up of patients under chronic therapy with infliximab is 6.6±4.7months on average (). Therefore, evidence for its sustained safety and efficacy is still lacking. Herein we report on a 34-year-old male patient with a long-standing neuro-BD who achieved a complete remission of the disease under infliximab monotherapy administrated every 6weeks.Infliximab monotherapy in Neuro-Behçet's disease: Four year follow-up in a long-standing case resistant to conventional therapiesAlfonso Fasano, Magda D'Agostino, Giacomo Caldarola, Claudio Feliciani, Clara De Simone10.1016/j.jneuroim.2011.08.014Journal of Neuroimmunology 239, 1 (2011)2011-09-12Journal of Neuroimmunology2011-09-122391-2S0165-5728(11)X0010-3Letter to the editor105107