Constitutive activity of NF-kappa B in myeloid cells drives pathogenicity of monocytes and macrophages during autoimmune neuroinflammation

The NF-κB/REL-family of transcription factors plays a central role in coordinating the expression of a wide variety of genes controlling immune responses including autoimmunity of the central nervous system (CNS). The inactive form of NF-κB consists of a heterodimer which is complexed with its inhibitor, IκB. Conditional knockout-mice for IκBα in myeloid cells (lysMCreIκBαfl/fl) have been generated and are characterized by a constitutive activation of NF-κB proteins allowing the study of this transcription factor in myelin-oligodendrocyte-glycoprotein induced experimental autoimmune encephalomyelitis (MOG-EAE), a well established experimental model for autoimmune demyelination of the CNS

Neurons are MHC Class I-Dependent Targets for CD8 T Cells upon Neurotropic Viral Infection

Following infection of the central nervous system (CNS), the immune system is faced with the challenge of eliminating the pathogen without causing significant damage to neurons, which have limited capacities of renewal. In particular, it was thought that neurons were protected from direct attack by cytotoxic T lymphocytes (CTL) because they do not express major histocompatibility class I (MHC I) molecules, at least at steady state. To date, most of our current knowledge on the specifics of neuron-CTL interaction is based on studies artificially inducing MHC I expression on neurons, loading them with exogenous peptide and applying CTL clones or lines often differentiated in culture. Thus, much remains to be uncovered regarding the modalities of the interaction between infected neurons and antiviral CD8 T cells in the course of a natural disease. Here, we used the model of neuroinflammation caused by neurotropic Borna disease virus (BDV), in which virus-specific CTL have been demonstrated as the main immune effectors triggering disease. We tested the pathogenic properties of brain-isolated CD8 T cells against pure neuronal cultures infected with BDV. We observed that BDV infection of cortical neurons triggered a significant up regulation of MHC I molecules, rendering them susceptible to recognition by antiviral CTL, freshly isolated from the brains of acutely infected rats. Using real-time imaging, we analyzed the spatio-temporal relationships between neurons and CTL. Brain-isolated CTL exhibited a reduced mobility and established stable contacts with BDV-infected neurons, in an antigen- and MHC-dependent manner. This interaction induced rapid morphological changes of the neurons, without immediate killing or impairment of electrical activity. Early signs of neuronal apoptosis were detected only hours after this initial contact. Thus, our results show that infected neurons can be recognized efficiently by brain-isolated antiviral CD8 T cells and uncover the unusual modalities of CTL-induced neuronal damage

Promoting remyelination in multiple sclerosis-recent advances

We review the current state of knowledge of remyelination in multiple sclerosis (MS), concentrating on advances in the understanding of the pathology and the regenerative response, and we summarise progress on the development of new therapies to enhance remyelination aimed at reducing progressive accumulation of disability in MS. We discuss key target pathways identified in experimental models, as although most identified targets have not yet progressed to the stage of being tested in human clinical trials, they may provide treatment strategies for demyelinating diseases in the future. Finally, we discuss some of the problems associated with testing this class of drugs, where they might fit into the therapeutic arsenal and the gaps in our knowledge

Difficulties in preventing repeated genital self-mutilation

© 2016, University of Kragujevac, Faculty of Science. All rights reserved. Self-mutilation is self-inflicted and intentional damage done to one’s body or one’s body parts without a conscious suicidal intention. The first case of genital self-mutilation was published in 1846, and the first scientific description of genital self-mutilation was written by Stroch in 1901. Since the first case has been described, there have been a relatively small number of described cases of genital self-mutilation in both genders; there have been an even smaller number of cases of repeated genital self-mutilation and only a few descriptions of repetitive forms of male genital self-mutilation in the literature. The aim of our study is to present difficulties in preventing repeated male genital self-mutilation of a patient with an intellectual disability who was diagnosed and treated for epilepsy and psychosis in early adult life and had a previous history of self-destructive behaviour during childhood. Previous literature does not contain many repeated cases of male genital self-mutilation. After evaluating the contribution of each individual factor in the aetiology of self-mutilation, we concluded that every individual factor is significant in the aetiology of selfmutilation; however, no single factor, as well as all the factors put together, is not enough for prevention of self-mutilation. Our conclusion is that all the presented factors in our research (intellectual disability, epilepsy, psychosis, self-destructive tendencies in childhood) have their place in the aetiology of male genital selfmutilation, but none of them are determining factors. This confirms that it is necessary to conduct further research in the field of aetiology of male genital self-mutilation, which would contribute towards more adequate prevention