Severity- and Time-Dependent Activation of Microglia in Spinal Cord Injury.

A spinal cord injury (SCI) initiates a number of cascades of biochemical reactions and intercellular interactions, the outcome of which determines the regenerative potential of the nervous tissue and opens up capacities for preserving its functions. The key elements of the above-mentioned processes are microglia. Many assumptions have been put forward, and the first evidence has been obtained, suggesting that, depending on the severity of SCI and the post-traumatic period, microglia behave differently. In this regard, we conducted a study to assess the microglia behavior in the model of mild, moderate and severe SCI in vitro for various post-traumatic periods. We reported for the first time that microglia make a significant contribution to both anti- and pro-inflammatory patterns for a prolonged period after severe SCI (60 dpi), while reduced severities of SCI do not lead to prolonged activation of microglia. The study also revealed the following trend: the greater the severity of the SCI, the lower the proliferative and phagocytic activity of microglia, which is true for all post-traumatic periods of SCI.

Immunogenic Properties of MVs Containing Structural Hantaviral Proteins: An Original Study.

Hemorrhagic fever with renal syndrome (HFRS) is an emerging infectious disease that remains a global public health threat. The highest incidence rate is among zoonotic disease cases in Russia. Most cases of HFRS are reported in the Volga region of Russia, which commonly identifies the Puumala virus (PUUV) as a pathogen. HFRS management is especially challenging due to the lack of specific treatments and vaccines. This study aims to develop new approaches for HFRS prevention. Our goal is to test the efficacy of microvesicles (MVs) as PUUV nucleocapsid (N) and glycoproteins (Gn/Gc) delivery vehicles. Our findings show that MVs could deliver the PUUV N and Gn/Gc proteins in vitro. We have also demonstrated that MVs loaded with PUUV proteins could elicit a specific humoral and cellular immune response in vivo. These data suggest that an MV-based vaccine could control HFRS.

Application of neurotrophic and proangiogenic factors as therapy after peripheral nervous system injury.

The intrinsic ability of peripheral nerves to regenerate after injury is extremely limited, especially in case of severe injury. This often leads to poor motor function and permanent disability. Existing approaches for the treatment of injured nerves do not provide appropriate conditions to support survival and growth of nerve cells. This drawback can be compensated by the use of gene therapy and cell therapy-based drugs that locally provide an increase in the key regulators of nerve growth, including neurotrophic factors and extracellular matrix proteins. Each growth factor plays its own specific angiotrophic or neurotrophic role. Currently, growth factors are widely studied as accelerators of nerve regeneration. Particularly noteworthy is synergy between various growth factors, that is essential for both angiogenesis and neurogenesis. Fibroblast growth factor 2 and vascular endothelial growth factor are widely known for their proangiogenic effects. At the same time, fibroblast growth factor 2 and vascular endothelial growth factor stimulate neural cell growth and play an important role in neurodegenerative diseases of the peripheral nervous system. Taken together, their neurotrophic and angiogenic properties have positive effect on the regeneration process. In this review we provide an in-depth overview of the role of fibroblast growth factor 2 and vascular endothelial growth factor in the regeneration of peripheral nerves, thus demonstrating their neurotherapeutic efficacy in improving neuron survival in the peripheral nervous system.

Increasing Severity of Spinal Cord Injury Results in Microglia/Macrophages With Annular-Shaped Morphology and No Change in Expression of CD40 and Tumor Growth Factor-ß During the Chronic Post-injury Stage.

Determination of the quantitative composition of phenotypically and morphologically different populations of resident microglia and infiltrating macrophages in spinal cord injury (SCI) of various degrees of severity could lead to much needed novel therapeutic interventions in neurotrauma. In this regard, we investigated the CD40 and TGF-ß expressing populations of microglia/macrophages and their morphological states in a rat model of SCI of varying severity. We are the first to describe the annular-shaped microglia/macrophages, the morphology of which was formed due to the spatial orientation of the processes that form round or oval micro-territories, which include disintegrating myelin fibers. This type of cell morphology was found only in the injured spinal cord and mainly in the white matter. At the same time, an assessment of the number of annular-shaped microglia/macrophages and the diameter of micro-territories formed by their processes showed an elevation in these indicators as the severity of SCI increased. While we did not find significant quantitative changes in the populations of Iba1+/CD40+ and Iba1+/TGF-ß+ microglia/macrophages with increased severity of SCI in the chronic period (60 dpi), we did determine changes in the expression of cytokines and mRNAs of genes-encoding microglial marker proteins, finding the greatest changes on days 7 and 14 after SCI between experimental groups with varying severity.

Bioinformatic Study of Transcriptome Changes in the Mice Lumbar Spinal Cord After the 30-Day Spaceflight and Subsequent 7-Day Readaptation on Earth: New Insights Into Molecular Mechanisms of the Hypogravity Motor Syndrome.

The hypogravity motor syndrome (HMS) is one of the deleterious impacts of weightlessness on the human body in orbital space missions. There is a hypothesis that disorders of musculoskeletal system as part of HMS arise in consequence of changes in spinal motor neurons. The study was aimed at bioinformatic analysis of transcriptome changes in lumbar spinal cords of mice after a 30-day spaceflight aboard biosatellite Bion-M1 (space group, S) and subsequent 7-day readaptation to the Earth's gravity (recovery group, R) when compared with control mice (C group) housed in simulated biosatellite conditions on the Earth. Gene ontology and human phenotype ontology databases were used to detect biological processes, molecular functions, cellular components, and human phenotypes associated with HMS. Our results suggest resemblance of molecular changes developing in space orbit and during the postflight recovery to terrestrial neuromuscular disorders. Remarkably, more prominent transcriptome changes were revealed in R vs. S and R vs. C comparisons that are possibly related to the 7-day recovery period in the Earth's gravity condition. These data may assist with establishment of HMS pathogenesis and proposing effective preventive and therapeutic options.