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.

Anatomical and Biochemical Traits Associated with Field Resistance of Onion Cultivars to Onion Thrips and the Effect of Mechanical Injury on the Level of Biochemical Compounds in Onion Leaves

Thrips tabaci Lind. is a global pest and also represents a serious threat to onion production in Poland. In 2 years (2015–2016) of field studies, 8 onion cultivars were evaluated to characterize the resistance to onion thrips and to determine if any biochemical and anatomical features of onion plants are associated with antixenotic and/or antibiotic mechanisms of resistance. Additionally, the influence of mechanical injury on the content of several biochemical compounds in onion leaves was made. The resistance to thrips colonization during the migration period, abundance, and thrips damage throughout the whole vegetation season was determined. We identified two cultivars, Tęcza and Wenta, resistant to thrips colonization and abundance, and one cultivar Wenta resistant to thrips damage. A positive correlation between concentrations of the reducing sugars and thrips abundance and conversely negative relationships between the total phenolic content and thrips damage was confirmed in both years. We suspect that a thinner epidermal layer, a smaller area of epidermal and mesophilic cells, and a lower diameter of vascular bundles may favor the resistance of onion cultivars to thrips. Thrips foraging resulted in a decrease in the content of soluble sugars, sucrose, and plant pigments in the leaves of all onion varieties.

Mechanical Stretching-Induced Traumatic Brain Injury Is Mediated by the Formation of GSK-3β-Tau Complex to Impair Insulin Signaling Transduction

Traumatic brain injury confers a significant and growing public health burden. It is a major environmental risk factor for dementia. Nonetheless, the mechanism by which primary mechanical injury leads to neurodegeneration and an increased risk of dementia-related diseases is unclear. Thus, we aimed to investigate the effect of stretching on SH-SY5Y neuroblastoma cells that proliferate in vitro. These cells retain the dopamine-β-hydroxylase activity, thus being suitable for neuromechanistic studies. SH-SY5Y cells were cultured on stretchable membranes. The culture conditions contained two groups, namely non-stretched (control) and stretched. They were subjected to cyclic stretching (6 and 24 h) and 25% elongation at 1 Hz. Following stretching at 25% and 1 Hz for 6 h, the mechanical injury changed the mitochondrial membrane potential and triggered oxidative DNA damage at 24 h. Stretching decreased the level of brain-derived neurotrophic factors and increased amyloid-β, thus indicating neuronal stress. Moreover, the mechanical injury downregulated the insulin pathway and upregulated glycogen synthase kinase 3β (GSK-3β)S9/p-Tau protein levels, which caused a neuronal injury. Following 6 and 24 h of stretching, GSK-3βS9 was directly bound to p-TauS396. In contrast, the neuronal injury was improved using GSK-3β inhibitor TWS119, which downregulated amyloid-β/p-Taus396 phosphorylation by enhancing ERK1/2T202/Y204 and AktS473 phosphorylation. Our findings imply that the neurons were under stress and that the inactivation of the GSK3β could alleviate this defect.

How the Severity and Mechanism of Recurrent Laryngeal Nerve Dysfunction during Monitored Thyroidectomy Impact on Postoperative Voice

Intraoperative neuromonitoring can qualify and quantify RLN function during thyroid surgery. This study investigated how the severity and mechanism of RLN dysfunction during monitored thyroid surgery affected postoperative voice. This retrospective study analyzed 1021 patients that received standardized monitored thyroidectomy. Patients had post-dissection RLN(R2) signal <50%, 50–90% and >90% decrease from pre-dissection RLN(R1) signal were classified into Group A-no/mild, B-moderate, and C-severe RLN dysfunction, respectively. Demographic characteristics, RLN injury mechanisms(mechanical/thermal) and voice analysis parameters were recorded. More patients in the group with higher severity of RLN dysfunction had malignant pathology results (A/B/C = 35%/48%/55%, p = 0.017), received neck dissection (A/B/C = 17%/31%/55%, p < 0.001), had thermal injury (p = 0.006), and had asymmetric vocal fold motion in long-term postoperative periods (A/B/C = 0%/8%/62%, p < 0.001). In postoperative periods, Group C patients had significantly worse voice outcomes in several voice parameters in comparison to Group A/B. Thermal injury was associated with larger voice impairments compared to mechanical injury. This report is the first to discuss the severity and mechanism of RLN dysfunction and postoperative voice in patients who received monitored thyroidectomy. To optimize voice and swallowing outcomes after thyroidectomy, avoiding thermal injury is mandatory, and mechanical injury must be identified early to avoid a more severe dysfunction.

Influence of overweight on the course of a mechanical injury

A literature review deals with the importance of overweight in victims with severe mechanical injury. Mechanical trauma remains an important medical and social problem for humanity. The course of injury and its consequences depend not only on the nature of the trauma, but also on the initial status of victim. The individual characteristics of the patient (gender, age, concomitant somatic pathology, etc.) and the treatment strategy are of great importance, in particular the timing and extent of surgical interventions. In this aspect, the role of overweight, which is a serious health problem worldwide, deserves attention. Many clinical studies and meta-analyses have shown the impact of overweight and obesity on the severity of certain injuries, the course of the post-traumatic period, the frequency of general and local complications, and mortality. Most studies have found that obesity is a marker of a negative prognosis in abdominal injury, and increases the risk of major complications and death. Obesity has been found to be a risk factor for wound complications, intra-abdominal hypertension and abdominal compartment syndrome, acute kidney injury, infectious complications, deep vein thrombosis, thromboembolism and pneumonia. Obese patients who underwent laparotomy for abdominal trauma had higher mortality, longer duration of hospital treatment, and longer duration of stay in the intensive care unit. In addition, obesity impedes interventional manipulations (the placement of the central venous catheter, tracheal intubation, ventilation) and surgical interventions (fracture stabilization, abdominal and thoracic interventions), and reduces the diagnostic value of traditional methods for examination of patients. The negative impact of overweight and obesity should be taken into account when planning diagnostic and treatment strategy, but needs to be further investigated.

Modeling links softening of myelin and spectrin scaffolds of axons after a concussion to increased vulnerability to repeated injuries

Damage to the microtubule lattice, which serves as a rigid cytoskeletal backbone for the axon, is a hallmark mechanical initiator of pathophysiology after concussion. Understanding the mechanical stress transfer from the brain tissue to the axonal cytoskeleton is essential to determine the microtubule lattice’s vulnerability to mechanical injury. Here, we develop an ultrastructural model of the axon’s cytoskeletal architecture to identify the components involved in the dynamic load transfer during injury. Corroborative in vivo studies were performed using a gyrencephalic swine model of concussion via single and repetitive head rotational acceleration. Computational analysis of the load transfer mechanism demonstrates that the myelin sheath and the actin/spectrin cortex play a significant role in effectively shielding the microtubules from tissue stress. We derive failure maps in the space spanned by tissue stress and stress rate to identify physiological conditions in which the microtubule lattice can rupture. We establish that a softer axonal cortex leads to a higher susceptibility of the microtubules to failure. Immunohistochemical examination of tissue from the swine model of single and repetitive concussion confirms the presence of postinjury spectrin degradation, with more extensive pathology observed following repetitive injury. Because the degradation of myelin and spectrin occurs over weeks following the first injury, we show that softening of the myelin layer and axonal cortex exposes the microtubules to higher stress during repeated incidences of traumatic brain injuries. Our predictions explain how mechanical injury predisposes axons to exacerbated responses to repeated injuries, as observed in vitro and in vivo.