Abstract

The use of mycophenolate mofetil (MMF) for a variety of immune-mediated diseases in veterinary medicine has been described. However, there is only a small number of cases documenting its use in dogs with meningoencephalomyelitis of unknown aetiology (MUE). We hypothesized that the use of MMF and corticosteroids in dogs with MUE results in comparable survival data to other published treatment protocols and is associated with limited adverse effects. A retrospective study of medical case records of dogs clinically diagnosed with MUE recorded signalment, neuroanatomic localization, magnetic resonance imaging findings, cerebrospinal fluid analysis results, medications administered, follow-up neurologic examinations, survival and adverse events. Variables were compared between dogs which were treated with MMF within 30 days of diagnosis (immediate group) vs. dogs in which MMF therapy was started >30 days after diagnosis (delayed group). Twenty-five cases of MUE were identified. The overall median survival time from diagnosis was 731 days (range 43–1672 days). After 1 month of MMF treatment, 92% of dogs showed improvement on a neurological examination. There was no significant effect of any recorded parameter on survival, including delayed vs. immediate initiation of MMF treatment. Dogs with delayed treatment had significantly lower clinical remission rates than dogs with immediate treatment at 6 months after starting MMF. Adverse events were identified in two cases (8%) and were characterized by mild gastrointestinal signs (vomiting and decreased appetite). Administration of MMF appears safe in dogs with MUE. The use of MMF results in comparable survival times to alternate immunosuppressive protocols.

Abstract

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.