Regeneration of the larval sea star nervous system by wounding induced respecification to the sox2 lineage

The ability to restore lost body parts following traumatic injury is a fascinating area of biology that challenges current understanding of the ontogeny of differentiation. The origin of new cells needed to regenerate lost tissue, and whether they are pluripotent stem cells, tissue-specific stem cells or have de- or trans- differentiated, remains one of the most important open questions in regeneration. Additionally, it is not clearly known whether developmental gene regulatory networks (GRNs) are reused to direct specification in these cells or whether regeneration specific networks are deployed. Echinoderms, including sea stars, have extensive ability for regeneration and have therefore been the subject of many thorough studies on the ultrastructural and molecular properties of cells needed for regeneration. However, the technologies for obtaining transgenic echinoderms are limited and tracking cells involved in regeneration, and thus identifying the cellular sources and potencies has proven challenging. In this study we develop new transgenic tools to follow the fate of populations of cells in the regenerating bipinnaria larva of the sea star Patira minaita. We show that the larval serotonergic nervous system can regenerate following decapitation. Using a BAC-transgenesis approach with photoconvertible fluorescent proteins, we show that expression of the pan ectodermal marker, sox2, is induced in previously sox2 minus cells at the wound site, even when cell division is inhibited. sox2+ cells give rise to new sox4+ neural precursors that then proceed along an embryonic neurogenesis pathway to reform the anterior nervous systems. sox2+ cells contribute to only neural and ectoderm lineages, indicating that these progenitors maintain their normal, embryonic lineage restriction. This indicates that sea star larval regeneration uses a combination of existing lineage restricted stem cells, as well as respecification of cells into neural lineages, and at least partial reuse of developmental GRNs to regenerate their nervous system.

A Levee to the Flood: Pre-injury Neuroinflammation and Immune Stress Influence Traumatic Brain Injury Outcome

Increasing evidence demonstrates that aging influences the brain's response to traumatic brain injury (TBI), setting the stage for neurodegenerative pathology like Alzheimer's disease (AD). This topic is often dominated by discussions of post-injury aging and inflammation, which can diminish the consideration of those same factors before TBI. In fact, pre-TBI aging and inflammation may be just as critical in mediating outcomes. For example, elderly individuals suffer from the highest rates of TBI of all severities. Additionally, pre-injury immune challenges or stressors may alter pathology and outcome independent of age. The inflammatory response to TBI is malleable and influenced by previous, coincident, and subsequent immune insults. Therefore, pre-existing conditions that elicit or include an inflammatory response could substantially influence the brain's ability to respond to traumatic injury and ultimately affect chronic outcome. The purpose of this review is to detail how age-related cellular and molecular changes, as well as genetic risk variants for AD affect the neuroinflammatory response to TBI. First, we will review the sources and pathology of neuroinflammation following TBI. Then, we will highlight the significance of age-related, endogenous sources of inflammation, including changes in cytokine expression, reactive oxygen species processing, and mitochondrial function. Heightened focus is placed on the mitochondria as an integral link between inflammation and various genetic risk factors for AD. Together, this review will compile current clinical and experimental research to highlight how pre-existing inflammatory changes associated with infection and stress, aging, and genetic risk factors can alter response to TBI.

A multilayer network model of neuron-astrocyte populations in vitro reveals mGluR5 inhibition is protective following traumatic injury

Astrocytes communicate bidirectionally with neurons, enhancing synaptic plasticity and promoting the synchronization of neuronal microcircuits. Despite recent advances in understanding neuron-astrocyte signaling, little is known about astrocytic modulation of neuronal activity at the population level, particularly in disease or following injury. We used high-speed calcium imaging of mixed cortical cultures in vitro to determine how population activity changes after disruption of glutamatergic signaling and mechanical injury. We constructed a multilayer network model of neuron-astrocyte connectivity, which captured distinct topology and response behavior from single cell type networks. mGluR5 inhibition decreased neuronal, but did not on its own disrupt functional connectivity or network topology. In contrast, injury increased the strength, clustering, and efficiency of neuronal but not astrocytic networks, an effect that was not observed in networks pre-treated with mGluR5 inhibition. Comparison of spatial and functional community structure revealed that functional connectivity is largely independent of spatial proximity at the microscale, but mechanical injury increased the spatial-functional correlation. Finally, we found that astrocyte segments of the same cell often belong to separate functional communities based on neuronal connectivity, suggesting that astrocyte segments function as independent entities. Our findings demonstrate the utility of multilayer network models for characterizing the multiscale connectivity of two distinct but functionally dependent cell populations.

Clinical Characteristics Associated with Physical Violence in the Elderly: A Retrospective Multicenter Analysis

Background: Elder abuse is predicted to increase with the rapid population ageing in many countries. Violent injury is influenced by individual factors as well as interpersonal and social relationships, with different manifestations based on changes in the socioeconomic position of older adults. We comparatively investigated the clinical and injury characteristics of physical violence in the elderly with those in another age group. Methods: We included elderly patients (age ≥65 years) who visited six emergency departments (ED) with violence-induced injuries in 2017. The control group comprised patients aged 45–64 years, selected by 1:2 matching based on hospital and sex. Data were extracted from the National Emergency Department Information System and electronic medical records. Both groups were compared for injury mechanism, injury location, activity during injury, diagnosis, and clinical outcomes. Results: Among the 316,944 patients who presented to the 6 ED, 89,178 (28.1%) had traumatic injuries, and 1.6% and 4.5% of injuries were sustained due to violence in the ≥65 and 45–64 year age groups, respectively. There were no significant intergroup differences in the perpetrator (P=0.27), body parts affected (P=0.63), and diagnosis (P=0.23), whereas the older adult group had a significantly higher proportion of traumatic injury by fall (P=0.01), at road and traffic facilities (P=0.01), during work (P=0.01), and multiple injuries (P<0.01). Conclusion: The increase in non-regular workers in the elderly after retirement may have increased the risk of traumatic workplace injuries. As workplace injuries may be a new risk factor for physical violence in the elderly, institutional workplace injury prevention policy is needed.

Identifying Blunt Force Traumatic Injury on Thermally Altered Remains: A Pilot Study Using Sus scrofa

In forensic scenarios involving homicide, human remains are often exposed to fire as a means of disposal and/or obscuring identity. Burning human remains can result in the concealment of traumatic injury, the creation of artifacts resembling injury, or the destruction of preexisting trauma. Since fire exposure can greatly influence trauma preservation, methods to differentiate trauma signatures from burning artifacts are necessary to conduct forensic analyses. Specifically, in the field of forensic anthropology, criteria to distinguish trauma from fire signatures on bone is inconsistent and sparse. This study aims to supplement current forensic anthropological literature by identifying criteria found to be the most diagnostic of fire damage or blunt force trauma. Using the skulls of 11 adult pigs (Sus scrofa), blunt force trauma was manually produced using a crowbar and flat-faced hammer. Three specimens received no impacts and were utilized as controls. All skulls were relocated to an outdoor, open-air fire where they were burned until a calcined state was achieved across all samples. Results from this experiment found that blunt force trauma signatures remained after burning and were identifiable in all samples where reassociation of fragments was possible. This study concludes that distinct patterns attributed to thermal fractures and blunt force fractures are identifiable, allowing for diagnostic criteria to be narrowed down for future analyses.

A Clinical Study on Traumatic Pericarditis and Traumatic Reticuloperitonitis in Twelve Holstein Friesian Cattle

Background: Traumatic injury caused by swallowed sharp foreign object is one of the common conditions in dairy animal resulting into development of traumatic pericarditis (TP) and traumatic reticuloperitonitis (TRP). Under field conditions both conditions mimic the same clinical signs making it difficult to differentiate as well as render to choose ideal therapeutic management. The present study was aimed to evaluate clinical, hematobiochemical and ultrasonographic changes in cattle to clinically differentiate between TP and TRP cases. Methods: From the period of January 2020 to December 2020, total twelve Holstein Friesian cattle were investigated for TP and TRP. In the present study, six animals each suffering from TP and TRP were included along with six normal healthy animals as control. Different clinical signs, haemato-biochemical parameters and ultrasonographical findings were recorded in each group and comparative analysis was done. Result: Brisket edema, bilateral jugular vein engorgement and arched back conditions were most reported clinical signs in both the groups. Significant changes were recorded in the values of red blood cells, lymphocyte, blood urea nitrogen, creatinine and SGOT between both the groups. Significant drop in hemoglobin level was observed in TP affected group. No significant changes were observed in white blood cells, packed cell volume, monocyte counts and eosinophil counts. Significant increase in fibrinogen concentration recorded in both the groups. In ultrasonography, accumulation of anechoic fluid around heart in TP and reticular wall thickening in TRP was most consistent findings.