In vivo imaging in autoimmune diseases in the central nervous system

Intravital imaging is becoming more popular and is being used to visualize cellular motility and functions. In contrast to in vitro analysis, which resembles in vivo analysis, intravital imaging can be used to observe and analyze cells directly in vivo. In this review, I will summarize recent imaging studies of autoreactive T cell infiltration into the central nervous system (CNS) and provide technical background. During their in vivo journey, autoreactive T cells interact with many different cells. At first, autoreactive T cells interact with endothelial cells in the airways of the lung or with splenocytes, where they acquire a migratory phenotype to infiltrate into the CNS. After arriving at the CNS, they interact with endothelial cells of the leptomeningeal vessels or the choroid plexus before passing through the blood-brain barrier. CNS-infiltrating T cells become activated by recognizing endogenous autoantigens presented by local antigen-presenting cells (APCs). This activation was visualized in vivo by using protein-based sensors. One such sensor detects changes in intracellular calcium concentration as an early marker of T cell activation. Another sensor detects translocation of Nuclear factor of activated T cells (NFAT) from cytosol to nucleus as a definitive sign of T cell activation. Importantly, intravital imaging is not just used to visualize cellular behavior. Together with precise analysis, intravital imaging deepens our knowledge of cellular functions in living organs and also provides a platform for developing therapeutic treatments

Collective Excitations and Nonequilibrium Phase Transition in Dissipative Fermionic Superfluids

We predict a new mechanism to induce collective excitations of a fermionic superfluid via sudden switch-on of two-body loss, for which we extend the BCS theory to fully incorporate quantum jumps. We find that such dissipation induces an amplitude oscillation of the superfluid order parameter accompanied by chirped phase rotation, which highlights the role of dissipation in a superfluid as a consequence of particle loss. We demonstrate that when the dissipation is introduced to one of the two superfluids coupled via a Josephson junction, it gives rise to a relative-phase mode analogous to the Leggett mode, which can be detected from time evolution of the Josephson current. We find that the coupled system exhibits a nonequilibrium dissipative phase transition characterized by the vanishing dc Josephson current. The dissipation-induced collective modes can be realized with ultracold fermionic atoms undergoing inelastic collisions.Comment: 13 pages, 7 figure

Post-CNS-inflammation expression of CXCL12 promotes the endogenous myelin/neuronal repair capacity following spontaneous recovery from multiple sclerosis-like disease

Background: Demyelination and axonal degeneration, hallmarks of multiple sclerosis (MS), are associated with the central nervous system (CNS) inflammation facilitated by C-X-C motif chemokine 12 (CXCL12) chemokine. Both in MS and in experimental autoimmune encephalomyelitis (EAE), the deleterious CNS inflammation has been associated with upregulation of CXCL12 expression in the CNS. We investigated the expression dynamics of CXCL12 in the CNS with progression of clinical EAE and following spontaneous recovery, with a focus on CXCL12 expression in the hippocampal neurogenic dentate gyrus (DG) and in the corpus callosum (CC) of spontaneously recovered mice, and its potential role in promoting the endogenous myelin/neuronal repair capacity. Methods: CNS tissue sections from mice with different clinical EAE phases or following spontaneous recovery and in vitro differentiated adult neural stem cell cultures were analyzed by immunofluorescent staining and confocal imaging for detecting and enumerating neuronal progenitor cells (NPCs) and oligodendrocyte precursor cells (OPCs) and for expression of CXCL12. Results: Our expression dynamics analysis of CXCL12 in the CNS with EAE progression revealed elevated CXCL12 expression in the DG and CC, which persistently increases following spontaneous recovery even though CNS inflammation has subsided. Correspondingly, the numbers of NPCs and OPCs in the DG and CC, respectively, of EAE-recovered mice increased compared to that of naive mice (NPCs, p 20 %) of the CXCL12(+) NPCs and OPCs co-express the CXCL12 receptor, CXCR4, and their numbers significantly increase with recovery from EAE not only relative to naive mice (p < 0.0002) but also to mice with ongoing EAE (p < 0.004). Conclusions: These data link CXCL12 expression in the DG and CC of EAE-recovering mice to the promotion of neuro/oligodendrogenesis generating CXCR4(+)CXCL12(+) neuronal and oligodendrocyte progenitor cells endowed with intrinsic neuro/oligondendroglial differentiation potential. These findings highlight the post-CNS-inflammation role of CXCL12 in augmenting the endogenous myelin/neuronal repair capacity in MS-like disease, likely via CXCL12/CXCR4 autocrine signaling

Live imaging of effector cell trafficking and autoantigen recognition within the unfolding autoimmune encephalomyelitis lesion

We tracked pathogenic myelin basic protein-specific CD4+ effector T cells in early central nervous system (CNS) lesions of experimental autoimmune encephalomyelitis (EAE) by combining two-photon imaging and fluorescence video microscopy. We made two key observations: (a) the majority of the cells (65%) moved fast (maximal speed 25 μm/min) and apparently nondirected through the compact tissue; and (b) a second group of effector T cells (35%) appeared tethered to a fixed point. Polarization of T cell receptor and adhesion molecules (lymphocyte function-associated antigen 1) towards this fixed point suggests the formation of immune synapses. Nonpathogenic, ovalbumin-specific T cells were not tethered in the CNS and did not form synapse-like contacts, but moved through the tissue. After intrathecal injection of antigen, 40% of ovalbumin-specific T cells became tethered. Conversely, injection of anti–major histocompatibility complex class II antibodies profoundly reduced the number of stationary pathogenic T cells within the CNS (to 15%). We propose that rapid penetration of the CNS parenchyma by numerous autoimmune effector T cells along with multiple autoantigen-presentation events are responsible for the fulminate development of clinical EAE

Pathological Examination of Experimentally Induced Periodontal Polyp in Mice

The mechanism in the formation of periodontal polyp has been established in several histological studies but details on cell differentiation and/or proliferation have not been elucidated. In the present study, we established a convenient and possible experimental system using ddY mice. Briefly, pentobarbital sodium (Somnopentyl) was injected into the abdominal cavity of the mouse followed by access cavity preparation on maxillary first molar using low speed ½ round bur (Merufa Inc), exposing the pulp and then allowed to perforate the floor of the pulp chamber. Observation was done over time until 6 months using micro CT (m_CT) image photography. Results with transmission image using m_CT showed theexpansion in the width of the periodontal ligament in the furcation area. The lesion was excised as one mass and examined histopathologically. The granulation tissue was covered with stratified squamous epithelium. The present experimental technique has been confirmed to be effective in analyzing the formation of periodontal polyp induced by mechanical perforation

Development of the WBL System to Complement Lectures for Teacher Professional Development

In this study, a Web Based-Learning system to complement lectures for teacher professional development was developed and evaluated by five points of view. The WBL courses using prior inference task were developed by Mashiko (2001) to exploit the lectures. The system including the courses had three function modes, (1) administrator mode, (2) learners mode and (3) instructor mode, are integrated using RDBMS. The learners estimated usefulness and practicability of the system for professional development of teachers especially the interaction in the online asynchronous forum with the face pictures of learners was valued.International Conference on Computers in Education (ICCE\u2702) , december 3-6, Auckland, New Zealan

Reactions to Bioabsorbable Suture Thread Embedded in Rat Subcutaneous Tissue

We examined the subcutaneous tissue reactions in rats to bioabsorbable suture thread using histopathological methods. Using Wister rats, Vicryl®, a bioabsorbable suture thread, was embedded into the subcutaneous tissue and histopathological examination was carried out after 4 weeks. Cholesterin crystals were used for the control. Furthermore, immunohistochemistry for CD68 was done. Histopathological examination showed proliferation of granulation tissues inboth experimental and control groups. The majority of cells in the granulation tissues were macrophages and giant cells. Fibroblasts were also observed in the proliferating granulation tissues surrounding the embedded bioabsorbable suturethread. Immunohistochemistry revealed that macrophages and giant cells were positive to CD68. The results suggest that the embedded bioabsorbable suture thread is not only fabricated to undergo absorption but also for phagocytosis bymacrophages and foreign body giant cells