Levels of small extracellular vesicles in patients treated with hyperbaric oxygenation.

Introduction: Hyperbaric oxygen (HBO2) therapy involves the inhalation of pure oxygen in a pressure chamber under increased ambient pressure. Recent research indicates that circulating small extracellular vesicles (sEVs) play important roles in human physiology and pathology. Therefore, the objective of this pilot study was to monitor the impact of HBO2 therapy on the levels of circulating sEVs in the serum of patients with necrotizing soft-tissue infections (NSTI), aseptic bone necrosis (ABN) or idiopathic sudden sensory neural hearing loss (ISSNHL). Material and methods: Serum-derived sEVs were isolated and quantified in 80 patients before and after HBO2 therapy applied for NSTI, ISSNHL and ABN patients as well as in normal controls who received neither HBO2 therapy nor steroids. Results: We observed a significant increase of circulating sEVs in patients with ISSNHL after HBO2 therapy (p < 0.05), as well as significantly elevated levels of sEVs after HBO2 therapy compared to patients with NSTI (p < 0.05) and ABN (p < 0.01). Conclusions: The increase in the levels of sEVs in ISSNHL may be evidence for both the intended reduction of inflammation as a result of steroid therapy and the inhibitory effect of oxidative stress induced by HBO2 therapy. Thus, sEVs released during HBO2 therapy might play an important biological role in mediating the response to therapy and might be a promising approach to gain further insights into the therapeutic efficacy of HBO2 therapy.

Modulation of LPS-Induced Neurodegeneration by Intestinal Helminth Infection in Ageing Mice.

Parasitic helminths induce a transient, short-term inflammation at the beginning of infection, but in persistent infection may suppress the systemic immune response by enhancing the activity of regulatory M2 macrophages. The aim of the study was to determine how nematode infection affects age-related neuroinflammation, especially macrophages in the nervous tissue. Here, intraperitoneal LPS-induced systemic inflammation resulting in brain neurodegeneration was enhanced by prolonged Heligmosomoides polygyrus infection in C57BL/6 mice. The changes in the brain coincided with the increase in M1 macrophages, reduced survivin level, enhanced APP and GFAP expression, chitin-like chains deposition in the brain and deterioration behaviour manifestations. These changes were also observed in transgenic C57BL/6 mice predisposed to develop neurodegeneration typical for Alzheimer's disease in response to pathogenic stimuli. Interestingly, in mice infected with the nematode only, the greater M2 macrophage population resulted in better results in the forced swim test. Given the growing burden of neurodegenerative diseases, understanding such interactive associations can have significant implications for ageing health strategies and disease monitoring.

Evaluation of the effects of hyperbaric on human attention functions based on eye movements recorded using an infrared camera.

BACKGROUND: This study aimed to assess the influence of elevated atmospheric pressure on the functions of attention of medical personnel working in hyperbaric chambers. We enrolled 15 participants who met the inclusion criteria. The test consisted of performing the same medical procedure under 2 conditions. For each of these test conditions, right eye movements were recorded using an oculograph. The obtained results revealed a relationship between elevated atmospheric pressure and the ability of medical personnel to focus. OBJECTIVES: To assess the influence of hyperbaric oxygen (HBO2) on visual attention in medical personnel during medical activities performed under normobaric (1 absolute atmosphere (1 ATA)) and hyperbaric (4 ATA) conditions inside a hyperbaric chamber. MATERIAL AND METHODS: Each participant had a valid license to act as a medical attendant during therapeutic hyperbaric sessions. Fifteen individuals, 10 men and 5 women aged between 28 and 65 years, participated in the study. The participants were asked to perform a medical procedure involving the preparation of a syringe with a drug administered by an infusion pump under 2 test conditions: 1 ATA corresponding to the atmospheric pressure on land, and 4 ATA corresponding to an underwater depth of 30 m. The order of test conditions was random. Both test conditions were performed inside a hyperbaric chamber. RESULTS: The number of fixations in the area of interest (AOI) varied between stages (1, 2 and 3) and task conditions (1 ATA and 4 ATA), with lower values for the 4 ATA condition. Under 1 ATA, 30% of eye fixations were in the AOI, as compared to only 6% under 4 ATA. CONCLUSIONS: The obtained results indicate that elevated atmospheric pressure has negative effects on the attention of medical personnel.

Global brain c-Fos profiling reveals major functional brain networks rearrangements after alcohol reexposure.

Many fundamental questions on alcohol use disorder (AUD) are frequently difficult to address by examining a single brain structure, but should be viewed from the whole brain perspective. c-Fos is a marker of neuronal activation. Global brain c-Fos profiling in rodents represents a promising platform to study brain functional networks rearrangements in AUD. We used a mouse model of alcohol drinking in IntelliCage. We trained mice to voluntarily drink alcohol, next subjected them to withdrawal and alcohol reexposure. We have developed a dedicated image computational workflow to identify c-Fos-positive cells in three-dimensional images obtained after whole-brain optical clearing and imaging in the light-sheet microscope. We provide a complete list of 169 brain structures with annotated c-Fos expression. We analyzed functional networks, brain modularity and engram index. Brain c-Fos levels in animals reexposed to alcohol were different from both control and binge drinking animals. Structures involved in reward processing, decision making and characteristic for addictive behaviors, such as precommissural nucleus, nucleus Raphe, parts of colliculus and tecta stood out particularly. Alcohol reexposure leads to a massive change of brain modularity including a formation of numerous smaller functional modules grouping structures involved in addiction development. Binge drinking can lead to substantial functional remodeling in the brain. We provide a list of structures that can be used as a target in pharmacotherapy but also point to the networks and modules that can hold therapeutic potential demonstrated by a clinical trial in patients.

Trends of stroke hospitalisation and fatality rates in young vs. elderly people in Poland during 2010-2019 decade.

INTRODUCTION: Since the turn of the century, epidemiological studies have shown an increase in stroke hospitalisation rates among young adults in contrast to a decline in rates seen among the older population. The aim of the present study was to investigate the trends of stroke hospitalisation rates and case fatality ratios (CFR) over the decade starting in 2010 in different age groups of the Polish population. MATERIAL AND METHODS: The patients were identified on the basis of the Polish National Health Fund that gathers all the data of the Hospital Discharge Registry as well as the National Cause of Death Registry of patients with stroke who were hospitalised between 2010 and 2019 and who were diagnosed according to the International Classification of Diseases - Tenth Revision (ICD-10) with haemorrhagic stroke (HS; codes I61* and I62*) and ischaemic stroke (IS; codes I63*). RESULTS: From a total nationwide cohort of 799,132 stroke patients (86.2% with IS and 13.8% with HS) treated between 2010 and 2019, a group of 22,329 patients (2.79%) aged 18-44 years was selected, among whom 69.6% had IS and 30.4% had HS. We documented a statistically significant increase in the IS hospitalisation rate in young adults alongside a decrease of this rate in those aged > 64. Among young adults with IS, the highest increase (p = 0.001) was observed for those aged 35-44 in 2019 (up to 39.2), and was significant each year starting from 2017 (2017-2019: p < 0.01). In the case of HS, the annual number of patients did not change significantly. In 2019 (compared to 2010), a decrease in 30-day, 90-day and 1-year CFR was noted in all age groups of patients with IS and HS. Stroke aetiology of IS was diagnosed in 60% of patients. More than 40% of patients with IS were discharged with the diagnosis of stroke of unspecified cause. CONCLUSIONS: In the case of IS, opposite trends of hospitalisation rates in younger and older age groups were documented, with the highest increase of IS in patients aged 35-44. A decline in CFR was observed for both IS and HS in all age groups.

Effectiveness of Hyperbaric Oxygen Therapy in SARS-CoV-2 Pneumonia: The Primary Results of a Randomised Clinical Trial.

Mortality in COVID-19 is mainly associated with respiratory failure, cytokine storm, and macrophage activation. Oxygenation and anti-inflammatory effects of Hyperbaric Oxygen Therapy (HBOT) suggest that it is a promising adjunct treatment for COVID-19. Repeated sessions of HBO with standard COVID-19 therapy were used to reduce the inflammation and increase oxygenation. We evaluated the safety and efficacy of HBOT in avoiding the replacement ventilation and/or ECMO and its effect on the inflammatory process. Twenty-eight moderate-to-severe COVID-19 patients were randomized into control or HBOT group. HBOT patients participated in 5 hyperbaric sessions (60 min). Before and after each session blood gas levels and vital parameters were monitored. Blood samples were collected for extended biochemical tests, blood morphology and immunological assays. There were 3 deaths in the control, no deaths in the HBOT group. No adverse events leading to discontinuation of HBOT were observed and patients receiving HBOT required lower oxygen delivery. We observed decrease in CRP, ferritin and LDH and increase in CD3 in HBOT group compared to control. This study confirmed the feasibility and safety of HBOT in patients with COVID-19 and indicated HBOT can lead to alleviation of inflammation and partial restoration of T cell responses.

Effect of Hyperbaric Oxygenation on Blood Cytokines and Arginine Derivatives; No Evidence for Induction of Inflammation or Endothelial Injury.

(1) Background: Hyperbaric oxygen therapy (HBOT) uses 100% oxygen delivered at 1.5-3 times the atmospheric pressure in a specialised chamber to achieve supraphysiological oxygen tension in blood and tissues. Besides its target, HBOT may affect inflammation, endothelial function or angiogenesis. This study analysed the effect of HBOT on blood concentrations of factors that may affect these processes in patients with necrotizing soft-tissue infections (NSTI), aseptic bone necrosis (ABN) and idiopathic sudden sensory neural hearing loss (ISSNHL). (2) Methods: Concentrations asymmetric dimethylarginine (ADMA) and other arginine derivatives were measured with liquid chromatography/mass spectrometry, whereas ELISA was used to quantitate vascular endothelial growth factor (VEGF) and cytokines (IL-1, IL-4, IL-6, IL-10, TGF-ß) before and after HBOT in 80 patients (NSTI n = 21, ISSNHL n = 53, ABN n = 6). (3) Results: While some differences were noted between patient groups in ADMA and other arginine derivatives as well as in cytokine concentrations, HBOT did not affect any of these parameters. (4) Conclusions: While cytokines and arginine derivatives concentrations were modified by underlying pathology, hyperbaric oxygenation did not immediately modify it suggesting that it is neutral for inflammation and is not inducing endothelial injury.

Afferent Connections of Cytoarchitectural Area 6M and Surrounding Cortex in the Marmoset: Putative Homologues of the Supplementary and Pre-supplementary Motor Areas.

Cortical projections to the caudomedial frontal cortex were studied using retrograde tracers in marmosets. We tested the hypothesis that cytoarchitectural area 6M includes homologues of the supplementary and pre-supplementary motor areas (SMA and pre-SMA) of other primates. We found that, irrespective of the injection sites' location within 6M, over half of the labeled neurons were located in motor and premotor areas. Other connections originated in prefrontal area 8b, ventral anterior and posterior cingulate areas, somatosensory areas (3a and 1-2), and areas on the rostral aspect of the dorsal posterior parietal cortex. Although the origin of afferents was similar, injections in rostral 6M received higher percentages of prefrontal afferents, and fewer somatosensory afferents, compared to caudal injections, compatible with differentiation into SMA and pre-SMA. Injections rostral to 6M (area 8b) revealed a very different set of connections, with increased emphasis on prefrontal and posterior cingulate afferents, and fewer parietal afferents. The connections of 6M were also quantitatively different from those of the primary motor cortex, dorsal premotor areas, and cingulate motor area 24d. These results show that the cortical motor control circuit is conserved in simian primates, indicating that marmosets can be valuable models for studying movement planning and control.

Histology-Based Average Template of the Marmoset Cortex With Probabilistic Localization of Cytoarchitectural Areas.

The rapid adoption of marmosets in neuroscience has created a demand for three dimensional (3D) atlases of the brain of this species to facilitate data integration in a common reference space. We report on a new open access template of the marmoset cortex (the Nencki-Monash, or NM template), representing a morphological average of 20 brains of young adult individuals, obtained by 3D reconstructions generated from Nissl-stained serial sections. The method used to generate the template takes into account morphological features of the individual brains, as well as the borders of clearly defined cytoarchitectural areas. This has resulted in a resource which allows direct estimates of the most likely coordinates of each cortical area, as well as quantification of the margins of error involved in assigning voxels to areas, and preserves quantitative information about the laminar structure of the cortex. We provide spatial transformations between the NM and other available marmoset brain templates, thus enabling integration with magnetic resonance imaging (MRI) and tracer-based connectivity data. The NM template combines some of the main advantages of histology-based atlases (e.g. information about the cytoarchitectural structure) with features more commonly associated with MRI-based templates (isotropic nature of the dataset, and probabilistic analyses). The underlying workflow may be found useful in the future development of 3D brain atlases that incorporate information about the variability of areas in species for which it may be impractical to ensure homogeneity of the sample in terms of age, sex and genetic background.

Open access resource for cellular-resolution analyses of corticocortical connectivity in the marmoset monkey.

Understanding the principles of neuronal connectivity requires tools for efficient quantification and visualization of large datasets. The primate cortex is particularly challenging due to its complex mosaic of areas, which in many cases lack clear boundaries. Here, we introduce a resource that allows exploration of results of 143 retrograde tracer injections in the marmoset neocortex. Data obtained in different animals are registered to a common stereotaxic space using an algorithm guided by expert delineation of histological borders, allowing accurate assignment of connections to areas despite interindividual variability. The resource incorporates tools for analyses relative to cytoarchitectural areas, including statistical properties such as the fraction of labeled neurons and the percentage of supragranular neurons. It also provides purely spatial (parcellation-free) data, based on the stereotaxic coordinates of 2 million labeled neurons. This resource helps bridge the gap between high-density cellular connectivity studies in rodents and imaging-based analyses of human brains.

Unidirectional monosynaptic connections from auditory areas to the primary visual cortex in the marmoset monkey.

Until the late twentieth century, it was believed that different sensory modalities were processed by largely independent pathways in the primate cortex, with cross-modal integration only occurring in specialized polysensory areas. This model was challenged by the finding that the peripheral representation of the primary visual cortex (V1) receives monosynaptic connections from areas of the auditory cortex in the macaque. However, auditory projections to V1 have not been reported in other primates. We investigated the existence of direct interconnections between V1 and auditory areas in the marmoset, a New World monkey. Labelled neurons in auditory cortex were observed following 4 out of 10 retrograde tracer injections involving V1. These projections to V1 originated in the caudal subdivisions of auditory cortex (primary auditory cortex, caudal belt and parabelt areas), and targeted parts of V1 that represent parafoveal and peripheral vision. Injections near the representation of the vertical meridian of the visual field labelled few or no cells in auditory cortex. We also placed 8 retrograde tracer injections involving core, belt and parabelt auditory areas, none of which revealed direct projections from V1. These results confirm the existence of a direct, nonreciprocal projection from auditory areas to V1 in a different primate species, which has evolved separately from the macaque for over 30 million years. The essential similarity of these observations between marmoset and macaque indicate that early-stage audiovisual integration is a shared characteristic of primate sensory processing.