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Cardiac arrest (CA) is a life-threatening condition that requires immediate medical attention. Considerable advances in resuscitation have led to an increasing number of patients who survive the initial arrest event. However, among this growing patient population, morbidity and mortality rates remain strikingly high. This has been attributed to post-CA syndrome of which an imbalanced immune response is a crucial component. Using a murine CA model, we have shown that a profound immunosuppressive phase, characterized by severe lymphopenia, ensues following the initial pro-inflammatory response after CA. In the current study, we found that T and B lymphopoiesis was greatly impaired, as evidenced by the rapid and marked depletion of double-positive T cells and pre-B cells in the thymus and bone marrow, respectively. Our data then demonstrated that pharmacologic suppression of glucocorticoid signaling after CA significantly attenuated lymphopoiesis impairment, thereby mitigating post-CA lymphopenia. Lastly, we showed that specific deletion of the glucocorticoid receptor in T or B cells largely prevented the CA-induced depletion of immature lymphocyte populations in the thymus or bone marrow, respectively. Together, our findings indicate that glucocorticoid signaling mediates post-CA impairment of lymphopoiesis, a key contributor to post-CA immunosuppression. [ABSTRACT FROM AUTHOR]

Excitotoxic cell death because of the massive release of glutamate and ATP contributes to the secondary extension of cellular and tissue loss following traumatic spinal cord injury (SCI). Evidence from blockage experiments suggests that over‐expression and activation of purinergic receptors, especially P2X7, produces excitotoxicity in neurodegenerative diseases and trauma of the central nervous system. We hypothesize that the down‐regulation of specific miRNAs after the SCI contributes to the over‐expression of P2X7 and that restorative strategies can be used to reduce the excitotoxic response. In the present study, we have employed bioinformatic analyses to identify microRNAs whose down‐regulation following SCI can be responsible for P2X7 over‐expression and excitotoxic activity. Additional luciferase assays validated microRNA‐135a‐5p (miR‐135a) as a posttranscriptional modulator of P2X7. Moreover, gene expression analysis in spinal cord samples from a rat SCI model confirmed that the decrease in miR‐135a expression correlated with P2X7 over‐expression after injury. Transfection of cultures of Neuro‐2a neuronal cell line with a miR‐135a inhibitory sequences (antagomiR‐135a), simulating the reduction of miR‐135a observed after SCI, resulted in the increase of P2X7 expression and the subsequent ATP‐dependent rise in intracellular calcium concentration. Conversely, a restorative strategy employing miR‐135a mimicked reduced P2X7 expression, attenuating the increase in intracellular calcium concentration that depends on this receptor and protecting cells from excitotoxic death. Therefore, we conclude that miR‐135a is a potential therapeutic target for SCI and that restoration of its expression may reduce the deleterious effects of ATP‐dependent excitotoxicity induced after a traumatic spinal cord injury. [ABSTRACT FROM AUTHOR]

Trauma to the spinal cord causes permanent disability to more than 180,000 people every year worldwide.The initial mechanical damage triggers a complex set of secondary events involving the neural, vascular, and immune systems that largely determine the functional outcome of the spinal cord injury (SCI). Cellular and biochemical mechanisms responsible for this secondary injury largely depend on activation and inactivation of specific gene programs. Recent studies indicate that microRNAs function as gene expression switches in key processes of the SCI. Microarray data from rodent contusion models reveal that SCI induces changes in the global microRNA expression patterns. Variations in microRNA abundance largely result from alterations in the expression of the cells at the damaged spinal cord. However, microRNA expression levels after SCI are also influenced by the infiltration of immune cells to the injury site and the death and migration of specific neural cells after injury. Evidences on the role of microRNAs in the SCI pathophysiology have come from different sources. Bioinformatic analysis of microarray data has been used to identify specific variations in microRNA expression underlying transcriptional changes in target genes, which are involved in key processes in the SCI. Direct evidences on the role of microRNAs in SCI are scarcer, although recent studies have identified several microRNAs (miR-21, miR-486, miR-20) involved in key mechanisms of the SCI such as cell death or astrogliosis, among others. From a clinical perspective, different evidences make clear that microRNAs can be potent therapeutic tools to manipulate cell state and molecular processes in order to enhance functional recovery. The present article reviews the actual knowledge on how injury affects microRNA expression and the meaning of these changes in the SCI pathophysiology, to finally explore the clinical potential of microRNAs in the SCI. [ABSTRACT FROM AUTHOR]

The mature mammalian brain has long been thought to be a structurally rigid, static organ since the era of Ramón y Cajal in the early 20th century. Evidence accumulated over the past three decades, however, has completely overturned this long-held view. We now know that new neurons and glia are continuously added to the brain at postnatal stages, even in mature adults of various mammalian species, including humans. Moreover, these newly added cells contribute to structural plasticity and play important roles in higher order brain function, as well as repair after damage. A major source of these new neurons and glia is neural stem cells (NSCs) that persist in specialized niches in the brain throughout life. With this new view, our understanding of normal brain physiology and interventional approaches to various brain disorders has changed markedly in recent years. This article provides a brief overview on the historical changes in our understanding of the developmental dynamics of neurogenesis and gliogenesis in the postnatal and adult mammalian brain and discusses the roles of NSCs and other progenitor populations in such cellular dynamics in health and disease of the postnatal mammalian brain. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cell Differentiation and Reversion Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cells and Disease., (© 2019 Wiley Periodicals, Inc.)