Oral Administration of Type I Interferon Modulates the Course of Experimental Allergic Neuritis

We investigated the effect of oral administration of type I interferon (IFN) in experimental allergic neuritis (EAN) in Lewis rats immunized with bovine peripheral nerve myelin. Starting at 7 days preceding immunization, rats were fed daily until sacrifice either with 5000 U rat IFN-α/β or mock-IFN. The clinical severity of EAN was significantly reduced in IFN-α/β fed animals compared to mock-IFN fed controls. Demyelination, but not inflammation, was decreased in IFN-α/β fed compared to mock-IFN fed rats at day 20 after immunization. In situ IFN-γ production and inflammation were reduced when evaluated by immunocytochemistry at day 13 after immunization. Spleen cells from IFN-α/β fed compared to mock-IFN fed EAN rats showed significantly reduced proliferation to stimulation with Con A or peripheral nerve myelin. IFN-γ production in draining lymph node cells was significantly reduced after stimulation with bovine peripheral nerve myelin. Our data suggest that oral administration of IFN-α/β reduces the severity of EAN, possibly by a reduction in production.     

Clinical abnormalities of the nipple-areola complex: The role of imaging

Clinical examination of the nipple is part of normal breast screening procedures. Abnormal processes of benign or malignant nature may be reflected by erythema, erosion, swelling or acquired inversion. In patients presenting with a persistent unilateral nipple lesion, it is advisable to collect a sample to exclude Paget's disease of the nipple, a rare form of ductal carcinoma in situ (DCIS). Imaging should be performed to detect breast cancer, which is found in more than 80% of cases, and determine its possible multifocal nature. Breast MRI is indicated if breast-conserving surgery is planned. The main differential diagnoses are erosive adenomatosis and eczema of the nipple. Acquired inverted nipple is generally of inflammatory origin. It is usually diagnosed by conventional breast examination but breast MRI can be helpful when in doubt about possible underlying neoplasia.     

Myelin ultrastructure of sciatic nerve in rat experimental autoimmune neuritis model and its correlation with associated protein expression

To explore the relationship of peripheral nerve ultrastructure and its associated protein expression in experimental autoimmune neuritis (EAN). EAN was established in Lewis rats using an emulsified mixture of P0 peptide 180-199, Mycobacterium tuberculosis, and incomplete Freund’s adjuvant. Rats immunized with saline solution were used as a control group. Sciatic nerve ultrastructure and immunofluorescence histopathology were measured at the neuromuscular severity peak on day 18 post-induction. Cell-specific protein markers were used for immunofluorescence histopathology staining to characterize sciatic nerve cells: CD3 (T cell), Iba-1 (microglia), S100 (myelin), and neurofilament 200 (axon). The results showed that swelling of the myelin lamellae, vesicular disorganization, separation of the myelin lamellae, and an attenuation or disappearance of the axon were observed by transmission electron microscopy in the EAN group. CD3 and Iba-1 increased significantly in the structures characterized by separation or swelling of the myelin lamellae, and increased slightly in the structures characterized by vesicular of the myelin lamellae, S100 decreased in the structures characterized by vesicular disorganization or separation of the myelin lamellae. And neurofilament 200 decreased in the structures characterized by separation of the myelin lamellae. Furthermore, we found that Iba1 were positive in the myelin sheath, and overlapped with S100, which significantly indicated that Schwann cells played as macrophage-like cells during the disease progression of ENA. Our findings may be a significant supplement for the knowledge of EAN model, and may offer a novel sight on the treatment of Guillain-Barré syndrome.     

Untangling syntactic and sensory processing: an ERP study of music perception

The present study investigated music-syntactic processing with chord sequences that ended on either regular or irregular chord functions. Sequences were composed such that perceived differences in the cognitive processing between syntactically regular and irregular chords could not be due to the sensory processing of acoustic factors like pitch repetition, pitch commonality (the major component of "sensory dissonance"), or roughness. Three experiments with independent groups of subjects were conducted: a behavioral experiment and two experiments using electroencephalography. Irregular chords elicited an early right anterior negativity (ERAN) in the event-related brain potentials (ERPs) under both task-relevant and task-irrelevant conditions. Behaviorally, participants detected around 75% of the irregular chords, indicating that these chords were only moderately salient. Nevertheless, the irregular chords reliably elicited clear ERP effects. Amateur musicians were slightly more sensitive to musical irregularities than nonmusicians, supporting previous studies demonstrating effects of musical training on music-syntactic processing. The findings indicate that the ERAN is an index of music-syntactic processing and that the ERAN can be elicited even when irregular chords are not detectable based on acoustical factors such as pitch repetition, sensory dissonance, or roughness.     

Experimental autoimmune neuritis induces differential microglia activation in the rat spinal cord

The reactive spatial and temporal activation pattern of parenchymal spinal cord microglia was analyzed in rat experimental autoimmune neuritis (EAN). We observed a differential activation of spinal cord microglial cells. A significant increase in ED1⁺ microglia predominantly located in the dorsal horn grey matter of lumbar and thoracic spinal cord levels was observed on Day 12. As revealed by morphological criteria and by staining with further activation markers [allograft inflammatory factor 1 (AIF-1), EMAPII, OX6, P2X₄R], reactive microglia did not reach a macrophage-like state of full activation. On Day 12, a significant proliferative response could be observed, affecting all spinal cord areas and including ED1⁺ microglial cells and a wide range of putative progenitor cells. Thus, in rat EAN, a reactive localized and distinct microglial activation correlating with a generalized proliferative response could be observed.     

Expression of interleukin-16 in sciatic nerves, spinal roots and spinal cords of experimental autoimmune neuritis rats

Experimental autoimmune neuritis (EAN) is a well-known animal model of Guillain-Barré Syndrome. In this study, we studied the spatiotemporal expression of interleukin-16 (IL-16) in the nervous system of EAN rats and pharmacological effects of minocycline on IL-16 expressions in EAN rats. In sciatic nerves and dorsal/ventral roots of EAN rats, IL-16⁺ cells, identified as macrophages and T cells, were mainly found to concentrate around blood vessels. However, in spinal cords, IL-16⁺ microglial cells were mainly found in lumbar dorsal horns. Massive IL-16⁺ cell accumulation in sciatic nerves and spinal roots was temporally correlated with severity of neurological signs of EAN. Furthermore, a strong correlation of IL-16⁺ cell accumulation with local demyelination in perivascular areas of sciatic nerves, and significant reduction of IL-16⁺ cell numbers in sciatic nerves and spinal cords by minocycline suggested a pathological contribution of IL-16⁺ cells in EAN. Taken together, robust IL-16⁺ cell accumulation in the nervous system and its temporal correlation with severity of neurological signs in EAN might suggest a pathological role of IL-16 in EAN, which makes IL-16 a potential pharmacological target.     

Toll-like receptor-2, CD14 and heat-shock protein 70 in inflammatory lesions of rat experimental autoimmune neuritis

Experimental autoimmune neuritis (EAN) is a well-known animal model of Guillain-Barré syndrome (GBS) characterized by inflammation and demyelination in the peripheral nervous system. Toll-like receptors (TLRs) together with their co-receptors form the first line of the self-defense, and play important roles in innate immune responses and inflammation. TLRs can be activated by endogenous ligands, like heat shock protein 70 (HSP70). In this study, we examined the spatiotemporal expressions of TLR2, CD14 and Hsp70 in EAN rats using immunohistochemistry and RT-PCR. A significant up-regulation of TLR2, CD14 and Hsp70 was seen in sciatic nerves of EAN rats and correlated with disease severity. Furthermore, activated macrophages were the main cellular resource of TLR2, CD14 and Hsp70 in EAN. Our results suggest that TLR2-, CD14- or Hsp70-based immunomodulation might have potential in the control of unwanted innate immune system activation in inflammatory neuropathies.     

Immunopathogenesis and treatment of the guillain-barré syndrome—part I

The etiology of the Guillain-Barré syndrome (GBS) still remains elusive. Recent years have witnessed important advances in the delineation of the mechanisms that may operate to produce nerve damage. Evidence gathered from cell biology, immunology, and immunopathology studies in patients with GBS and animals with experimental autoimmune neuritis (EAN) indicate that GBS results from aberrant immune responses against components of peripheral nerve. Autoreactive T lymphocytes specific for the myelin antigens PO and P2 and circulating antibodies to these antigens and various glycoproteins and glycolipids have been indentified but their pathogenic role remains unclear. The multiplicity of these factors and the involvement of several antigen nonspecific proinflammatory mechanisms suggest that a complex interaction of immune pathways results in nerve damage. Data on disturbed humoral immunity with particular emphasis on glycolipid antibodies and on activation of autoreactive T lymphocytes and macrophages will be reviewed. Possible mechanisms underlying initiation of peripheral nerve-directed immune responses will be discussed with particular emphasis on the recently highlighted association with Campylobacter jejuni infection.© 1995 John Wiley &Sons, Inc.     

TNF-α receptor 1 deficiency reduces antigen-presenting capacity of Schwann cells and ameliorates experimental autoimmune neuritis in mice

Tumor necrosis factor-α (TNF-α) is a pleiotropic pro-inflammatory cytokine with potentially neurodestructive effects and plays a pivotal role in autoimmune demyelinating disease. To address the role of TNF-α in the pathogenesis of experimental autoimmune neuritis (EAN), the current study investigated the antigen-presenting capacity of Schwann cells (SCs) in EAN induced by P0 protein peptide 106–125 in TNF-α recepter 1 deficient (TNFR1^−/−) mice. The antigen-presenting capacity of SCs was assessed by the expression of MHC class II (MHCII), CD40, CD80 and CD86 molecules on activated SCs as well as by induction of T cell proliferation in co-cultures of P0 protein peptide 106–125 specific T cells with activated SCs. In addition, the expression of inducible nitric oxide synthase (iNOS) was measured in activated SCs by flow cytometry. TNFR1^−/− EAN mice developed significantly delayed and reduced clinical signs of EAN compared to wild type EAN mice. In parallel, the expression of MHCII, CD80 and iNOS on SCs were decreased in TNFR1^−/− mice compared to wild type mice. Likewise, proliferation of P0 protein peptide 106–125 specific T cells simulated by activated SCs of TNFR1^−/− EAN mice was lower than that of wild type EAN mice. Our data suggest that TNF-α may exert pro-inflammatory effects in EAN via TNFR1 by up-regulating the antigen-presenting function and iNOS production of SCs.