Croatian medical journal
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Croatian medical journal · Apr 2019
ReviewNecroptosis is one of the modalities of cell death accompanying ischemic brain stroke: from pathogenesis to therapeutic possibilities.
Due to very limited therapeutic options, ischemic brain injury is one of the leading causes of death and lifelong disability worldwide, which imposes enormous public health burden. One of the main events occurring with ischemic brain stroke is cell death. Necroptosis is a type of cell death described as a regulated necrosis characterized by cell membrane disruption mediated by phosphorylated mixed lineage kinase like protein (MLKL). ⋯ We also review articles describing positive effects obtained by reducing necroptosis, including the reduction of infarct volume and improved functional recovery in animal models. Since necroptosis is characterized by cell content leakage and subsequent inflammation, in addition to reducing cell death, inhibition of necroptosis in ischemic brain stroke also reduces some inflammatory cytokines. By comparing various approaches in inhibition of necroptosis, we analyze the achieved effects from the perspective of controlling necroptosis as a part of future therapeutic interventions in brain ischemia.
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Croatian medical journal · Apr 2019
ReviewSex differences in early communication development: behavioral and neurobiological indicators of more vulnerable communication system development in boys.
Perhaps due to different roles they have had in social groups during evolution, men and women differ in their verbal abilities. These differences are also (if not even more) present in children, both in the course of typical and pathological development. Beside the fact that girls have a well-documented advantage in early language development, almost all developmental disorders primarily affecting communication, speech, and language skills are more frequent in boys. ⋯ The aim of this review is to present the sex differences in typical communication and language development and in the prevalence of communication-related neurodevelopmental disorders. Also, a special focus is put on data from the field of neuroscience that might provide insight into the neurobiological mechanisms that can add to the understanding of this phenomenon. We argue that the functional organization of the female brain gives women an inherent advantage in the acquisition of communication and language system over men.
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Increasing evidence suggests that B cells contribute both to the regulation of normal autoimmunity and to the pathogenesis of immune mediated diseases, including multiple sclerosis (MS). B cells in MS are skewed toward a pro-inflammatory profile, and contribute to MS pathogenesis by antibody production, antigen presentation, T cells stimulation and activation, driving autoproliferation of brain-homing autoreactive CD4+ T cells, production of pro-inflammatory cytokines, and formation of ectopic meningeal germinal centers that drive cortical pathology and contribute to neurological disability. The recent interest in the key role of B cells in MS has been evoked by the profound anti-inflammatory effects of rituximab, a chimeric monoclonal antibody (mAb) targeting the B cell surface marker CD20, observed in relapsing-remitting MS. ⋯ Another promising approach is the inhibition of Bruton's tyrosine kinase, a key enzyme that mediates B cell activation and survival, by agents such as evobrutinib. On the other hand, targeting B cell cytokines with the fusion protein atacicept increased MS activity, highlighting the complex and not fully understood role of B cells and humoral immunity in MS. Finally, all other approved therapies for MS, some of which have been designed to target T cells, have some effects on the frequency, phenotype, or homing of B cells, which may contribute to their therapeutic activity.
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Croatian medical journal · Apr 2019
ReviewGlia in amyotrophic lateral sclerosis and spinal cord injury: common therapeutic targets.
The toolkit for repairing damaged neurons in amyotrophic lateral sclerosis (ALS) and spinal cord injury (SCI) is extremely limited. Here, we reviewed the in vitro and in vivo studies and clinical trials on nonneuronal cells in the neurodegenerative processes common to both these conditions. ⋯ Given the fundamental regulatory functions of glia, pathogenic mechanisms in neuroinflammation represent promising therapeutic targets. We also discussed neuroprotective, immunosuppressive, and stem-cell based approaches applicable to both ALS and SCI.