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

2022 ◽  
pp. 1-46
Author(s):  
Margaret E. Schroeder ◽  
Danielle S. Bassett ◽  
David F. Meaney
Keyword(s):  
Functional Connectivity ◽  
Network Model ◽  
High Speed ◽  
Traumatic Injury ◽  
Population Level ◽  
Mechanical Injury ◽  
Spatial Proximity ◽  
Multilayer Network ◽  
Population Activity

Abstract 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.

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

2019 ◽  
Author(s):  
M.E. Schroeder ◽  
D. S. Bassett ◽  
D. F. Meaney
Keyword(s):  
Network Model ◽  
High Speed ◽  
Traumatic Injury ◽  
Network Models ◽  
Population Level ◽  
Multilayer Network ◽  
Population Activity ◽  
Functional Community ◽  
Single Cell Type

AbstractDespite 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 signaling and mechanical injury. We constructed a multilayer network model of neuron-astrocyte connectivity, which captured unique topology and response behavior not evident from analysis of single cell type networks. mGluR5 inhibition decreased neuronal, but not astrocytic, activity and functional connectivity following traumatic injury, and also altered higher-order topological properties of multilayer networks. Comparison of spatial and functional community structure revealed that astrocyte segments of the same cell often belong to separate functional communities based on neural connectivity. Our findings demonstrate the utility of multilayer network models for characterizing the multiscale connectivity of two distinct but functionally dependent cell populations.

Method to enhance traffic capacity for multilayer networks

2020 ◽  
Vol 34 (13) ◽  
pp. 2050140
Author(s):  
Yongqiang Zhang ◽  
Yaming Li ◽  
Min Li ◽  
Jinlong Ma
Keyword(s):  
Network Model ◽  
High Speed ◽  
Great Influence ◽  
Packet Transmission ◽  
Multilayer Network ◽  
Transmission Effect ◽  
Traffic Capacity ◽  
Network Load ◽  
Simulation Results ◽  
High Degree

The network structure acquires great influence on the traffic capacity for complex network. Since the nodes with high degree usually bear large load in the process of packet transmission, we propose a new multilayer network model which can balance the load of low-speed and high-speed layers. The simulation results show that compared with the randomly select nodes multilayer network model, the new network model makes the multilayer network load more balanced, thereby enhancing traffic capacity of the network and reducing the possibility of congestion. This network model gives full play to the transmission advantages of the high-speed layer of the multilayer network, and can reduce the consumption of resources while achieving the same transmission effect, which is of guiding significance for the planning of network lines.

TRAUMATIC INJURY OF ASTROCYTES: AN IN VITRO STUDY

2018 ◽  
Vol 18 (04) ◽  
pp. 1850040
Author(s):  
YI HUA ◽  
CHRISTINA L. WILSON ◽  
SHENGMAO LIN ◽  
DIGANTA DUTTA ◽  
SRIVATSAN KIDAMBI ◽  
...  
Keyword(s):  
High Speed ◽  
Imaging System ◽  
Traumatic Injury ◽  
High Speed Imaging ◽  
Response Curves ◽  
Cortical Astrocytes ◽  
Strain And Strain Rate ◽  
Wide Range ◽  
Membrane Strain

The objective of this work is to determine the injury criterion for primary rat cortical astrocytes through an in vitro traumatic injury model. The compressed air pressure was used to reproduce typical blast pressure profile, which could induce biaxial strain up to 100% in millisecond for cells cultured on flexible membrane utilizing a controlled cellular injury (CCI) device. The nominal pressure and time settings could be adjusted to accommodate a wide range of membrane strain and strain rate, which was estimated from finite element models. The relationship between the peak membrane displacement/strain and the nominal settings of the CCI device was then established. The model was calibrated using both high-speed imaging system and a theoretical model. The viability and morphology of the astrocytes were characterized and correlated with the strain level. Three different regimes were identified in the stretch-induced dose-response curves of the primary cortical astrocytes, with a sharp decline from live to dead in a narrow range of membrane strain (18%–35%). The level of actin organization of the astrocytes decreased as the membrane strain increased. This work could facilitate the understanding of cellar behaviors subjected to mild blast loadings and the potential tissue engineering therapeutics.

scholarly journals Disulfide HMGB1 acts via TLR2/4 receptors to reduce the numbers of oligodendrocyte progenitor cells after traumatic injury in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
R. Ved ◽  
F. Sharouf ◽  
B. Harari ◽  
M. Muzaffar ◽  
S. Manivannan ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Culture Medium ◽  
Traumatic Injury ◽  
High Mobility ◽  
Oligodendrocyte Progenitor Cells ◽  
Therapeutic Approaches ◽  
Mature Oligodendrocyte ◽  
Oligodendrocyte Progenitor ◽  
Tlr Signalling

AbstractTraumatic brain injury (TBI) is associated with poor clinical outcomes; autopsy studies of TBI victims demonstrate significant oligodendrocyte progenitor cell (OPC) death post TBI; an observation, which may explain the lack of meaningful repair of injured axons. Whilst high-mobility group box-1 (HMGB1) and its key receptors TLR2/4 are identified as key initiators of neuroinflammation post-TBI, they have been identified as attractive targets for development of novel therapeutic approaches to improve post-TBI clinical outcomes. In this report we establish unequivocal evidence that HMGB1 released in vitro impairs OPC response to mechanical injury; an effect that is pharmacologically reversible. We show that needle scratch injury hyper-acutely induced microglial HMGB1 nucleus-to-cytoplasm translocation and subsequent release into culture medium. Application of injury-conditioned media resulted in significant decreases in OPC number through anti-proliferative effects. This effect was reversed by co-treatment with the TLR2/4 receptor antagonist BoxA. Furthermore, whilst injury conditioned medium drove OPCs towards an activated reactive morphology, this was also abolished after BoxA co-treatment. We conclude that HMGB1, through TLR2/4 dependant mechanisms, may be detrimental to OPC proliferation following injury in vitro, negatively affecting the potential for restoring a mature oligodendrocyte population, and subsequent axonal remyelination. Further study is required to assess how HMGB1-TLR signalling influences OPC maturation and myelination capacity.

scholarly journals NeuroHeal Improves Muscle Regeneration after Injury

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 22
Author(s):  
Sara Marmolejo-Martínez-Artesero ◽  
David Romeo-Guitart ◽  
Vanesa Venegas ◽  
Mario Marotta ◽  
Caty Casas
Keyword(s):  
Satellite Cell ◽  
Muscle Regeneration ◽  
Cell Biology ◽  
Fiber Type ◽  
Traumatic Injury ◽  
Injury Rate ◽  
Scar Tissue ◽  
Medical Problem ◽  
Preclinical Model

Musculoskeletal injuries represent a challenging medical problem. Although the skeletal muscle is able to regenerate and recover after injury, the process engaged with conservative therapy can be inefficient, leading to a high re-injury rate. In addition, the formation of scar tissue implies an alteration of mechanical properties in muscle. There is still a need for new treatments of the injured muscle. NeuroHeal may be one option. Published studies demonstrated that it reduces muscle atrophy due to denervation and disuse. The main objective of the present work was to assess the potential of NeuroHeal to improve muscle regeneration after traumatic injury. Secondary objectives included characterizing the effect of NeuroHeal treatment on satellite cell biology. We used a rat model of sport-induced injury in the gastrocnemius and analyzed the effects of NeuroHeal on functional recovery by means of electrophysiology and tetanic force analysis. These studies were accompanied by immunohistochemistry of the injured muscle to analyze fibrosis, satellite cell state, and fiber type. In addition, we used an in vitro model to determine the effect of NeuroHeal on myoblast biology and partially decipher its mechanism of action. The results showed that NeuroHeal treatment advanced muscle fiber recovery after injury in a preclinical model of muscle injury, and significantly reduced the formation of scar tissue. In vitro, we observed that NeuroHeal accelerated the formation of myotubes. The results pave the way for novel therapeutic avenues for muscle/tendinous disorders.

scholarly journals Influence of hinge length and distribution number on the camber and cornering properties of a non-pneumatic tire

2020 ◽  
Vol 12 (12) ◽  
pp. 168781402098468
Author(s):  
Xianbin Du ◽  
Youqun Zhao ◽  
Yijiang Ma ◽  
Hongxun Fu
Keyword(s):  
Neural Network ◽  
Network Model ◽  
Adaptive Learning ◽  
High Speed ◽  
Back Propagation ◽  
Lateral Force ◽  
Learning Ability ◽  
Vehicle Performance ◽  
Neural Network Theory ◽  
Bp Neural Network Model

The camber and cornering properties of the tire directly affect the handling stability of vehicles, especially in emergencies such as high-speed cornering and obstacle avoidance. The structural and load-bearing mode of non-pneumatic mechanical elastic (ME) wheel determine that the mechanical properties of ME wheel will change when different combinations of hinge length and distribution number are adopted. The camber and cornering properties of ME wheel with different hinge lengths and distributions were studied by combining finite element method (FEM) with neural network theory. A ME wheel back propagation (BP) neural network model was established, and the additional momentum method and adaptive learning rate method were utilized to improve BP algorithm. The learning ability and generalization ability of the network model were verified by comparing the output values with the actual input values. The camber and cornering properties of ME wheel were analyzed when the hinge length and distribution changed. The results showed the variation of lateral force and aligning torque of different wheel structures under the combined conditions, and also provided guidance for the matching of wheel and vehicle performance.

scholarly journals Turnover of the Active Fraction of IRS1 Involves Raptor-mTOR- and S6K1-Dependent Serine Phosphorylation in Cell Culture Models of Tuberous Sclerosis

2006 ◽  
Vol 26 (17) ◽  
pp. 6425-6434 ◽  
Author(s):  
O. Jameel Shah ◽  
Tony Hunter
Keyword(s):  
Cell Culture ◽  
Tuberous Sclerosis ◽  
High Speed ◽  
Serine Phosphorylation ◽  
Feedback Signal ◽  
Insulin Receptor Substrates ◽  
Igf I ◽  
Culture Models ◽  
Cell Culture Models

ABSTRACT The TSC1-TSC2/Rheb/Raptor-mTOR/S6K1 cell growth cassette has recently been shown to regulate cell autonomous insulin and insulin-like growth factor I (IGF-I) sensitivity by transducing a negative feedback signal that targets insulin receptor substrates 1 and 2 (IRS1 and -2). Using two cell culture models of the familial hamartoma syndrome, tuberous sclerosis, we show here that Raptor-mTOR and S6K1 are required for phosphorylation of IRS1 at a subset of serine residues frequently associated with insulin resistance, including S307, S312, S527, S616, and S636 (of human IRS1). Using loss- and gain-of-function S6K1 constructs, we demonstrate a requirement for the catalytic activity of S6K1 in both direct and indirect regulation of IRS1 serine phosphorylation. S6K1 phosphorylates IRS1 in vitro on multiple residues showing strong preference for RXRXXS/T over S/T,P sites. IRS1 is preferentially depleted from the high-speed pellet fraction in TSC1/2-deficient mouse embryo fibroblasts or in HEK293/293T cells overexpressing Rheb. These studies suggest that, through serine phosphorylation, Raptor-mTOR and S6K1 cell autonomously promote the depletion of IRS1 from specific intracellular pools in pathological states of insulin and IGF-I resistance and thus potentially in lesions associated with tuberous sclerosis.

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