Traumatic injury elicits JNK-mediated human astrocyte retraction in vitro

Neuroscience ◽  
2014 ◽  
Vol 274 ◽  
pp. 1-10 ◽  
Author(s):  
C. Augustine ◽  
G. Cepinskas ◽  
D.D. Fraser
Keyword(s):  
Traumatic Injury ◽  
Human Astrocyte

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 Palm Fruit Bioactives modulate human astrocyte activity in vitro altering the cytokine secretome reducing levels of TNFα, RANTES and IP-10

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Robert P. Weinberg ◽  
Vera V. Koledova ◽  
Kirsten Schneider ◽  
T. G. Sambandan ◽  
Adlai Grayson ◽  
...  
Keyword(s):  
Palm Fruit ◽  
Human Astrocyte

Passive Mechanical Analysis of Engineered Myotube Fibers

2009 ◽  
Author(s):  
Ryan A. Koppes ◽  
Nathan R. Schiele ◽  
Douglas M. Swank ◽  
Douglas B. Chrisey ◽  
David T. Corr
Keyword(s):  
Mechanical Properties ◽  
Genetic Disease ◽  
Traumatic Injury ◽  
Mechanical Analysis ◽  
Muscular Tissue ◽  
Surgical Excisions ◽  
Potential Remedy ◽  
Cell Versus

The loss of functional muscle as a product of genetic disease, traumatic injury, or surgical excisions results in a physiological deficiency that still remains without an effective clinical treatment [1]. Engineering of functional tissue in vitro for replacement in vivo might pose as a potential remedy for this clinical demand. By approaching tissue engineering from the bottom-up, geometrically directing myoblast growth provides a means for constructing tissue replacements cell-by-cell versus the traditional decellularized construct that remains limited by its size and ability to deliver cellular nutrients. Furthermore, geometrically controlling the growth of myoblasts allows for direct manipulation of the structural and mechanical properties inherent to muscular tissue.

Proliferation of Cells From a Mouse Model of Regeneration

2013 ◽  
Author(s):  
Kristen Lynch ◽  
Tabassum Ahsan
Keyword(s):  
Regenerative Medicine ◽  
Stromal Cells ◽  
Military Veterans ◽  
Traumatic Injury ◽  
Limb Regeneration ◽  
Specific Response ◽  
Complex Structures ◽  
Epimorphic Regeneration ◽  
In Vitro Techniques

The ability to induce limb regeneration in humans is of growing interest in the field of regenerative medicine, particularly due to the increased number of amputees among military veterans. Unfortunately, mammals have limited regenerative capabilities as compared to amphibians, which can re-establish complex structures after traumatic injury. There have been a few clinically documented cases of digit regeneration in children [1], indicating that the potential to regenerate is not completely absent in humans. Mammalian models of epimorphic regeneration is primarily limited to the mouse digit, which has a level-specific response in that amputation at the terminal phalangeal element (P3) results in regeneration, but not at the next more proximal joint (P2) (Figure 1). Recently primary stromal cells were isolated from each of these mouse joints (P3 and P2, respectively) [2], which provides a unique opportunity to utilize in vitro techniques to identify differences in one of the phenotypes prevalent at the amputation plane of a regenerating and non-regenerating region.

The AMPAR antagonist perampanel regulates neuronal necroptosis via Akt/GSK3β signaling after acute traumatic injury in cortical neurons

2020 ◽  
Vol 19 ◽  
Author(s):  
Tao Chen ◽  
Li-Kun Yang ◽  
Jie Zhu ◽  
Chun-Hua Hang ◽  
Yu-Hai Wang
Keyword(s):  
Traumatic Brain Injury ◽  
Protective Effect ◽  
Neuronal Death ◽  
Cortical Neurons ◽  
Therapeutic Potential ◽  
Traumatic Injury ◽  
Neuroprotective Effects ◽  
Stroke Models ◽  
Cultured Cortical Neurons

Background: Perampanel is a highly selective and non-competitive α-amino-3-hydroxy-5 -methyl-4-isoxazole propionate (AMPA) receptor (AMPAR) antagonist, which has been licensed as an orally administered antiepileptic drug in more than 55 countries. Recently, perampanel was found to exert neuroprotective effects in hemorrhagic and ischemic stroke models. Objective: In this study, the protective effect of perampanel was investigated. Method: The protective effect of perampanel was investigated in an in vitro traumatic neuronal injury (TNI) model in primary cultured cortical neurons. Conclusion: Our present data suggest that necroptosis plays a key role in the pathogenesis of neuronal death after TNI, and that perampanel might have therapeutic potential for patients with traumatic brain injury (TBI).

scholarly journals Differentiated HASTR/ci35 cells: A promising in vitro human astrocyte model for facilitating CNS drug development studies

2018 ◽  
Vol 137 (4) ◽  
pp. 350-358 ◽  
Author(s):  
Keita Kitamura ◽  
Ryo Ito ◽  
Kenta Umehara ◽  
Hanae Morio ◽  
Kosuke Saito ◽  
...  
Keyword(s):  
Drug Development ◽  
Development Studies ◽  
Human Astrocyte

scholarly journals Facilitating Reparative Dentin Formation Using Apigenin Local Delivery in the Exposed Pulp Cavity

2021 ◽  
Vol 12 ◽  
Author(s):  
Yam Prasad Aryal ◽  
Chang-Yeol Yeon ◽  
Tae-Young Kim ◽  
Eui-Seon Lee ◽  
Shijin Sung ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Traumatic Injury ◽  
Local Delivery ◽  
Protease Production ◽  
Mice Model ◽  
Reparative Dentin ◽  
Dentin Formation ◽  
Reparative Dentin Formation

Apigenin, a natural product belonging to the flavone class, affects various cell physiologies, such as cell signaling, inflammation, proliferation, migration, and protease production. In this study, apigenin was applied to mouse molar pulp after mechanically pulpal exposure to examine the detailed function of apigenin in regulating pulpal inflammation and tertiary dentin formation. In vitro cell cultivation using human dental pulp stem cells (hDPSCs) and in vivo mice model experiments were employed to examine the effect of apigenin in the pulp and dentin regeneration. In vitro cultivation of hDPSCs with apigenin treatment upregulated bone morphogenetic protein (BMP)- and osteogenesis-related signaling molecules such as BMP2, BMP4, BMP7, bone sialoprotein (BSP), runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN) after 14 days. After apigenin local delivery in the mice pulpal cavity, histology and cellular physiology, such as the modulation of inflammation and differentiation, were examined using histology and immunostainings. Apigenin-treated specimens showed period-altered immunolocalization patterns of tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), NESTIN, and transforming growth factor (TGF)-β1 at 3 and 5 days. Moreover, the apigenin-treated group showed a facilitated dentin-bridge formation with few irregular tubules after 42 days from pulpal cavity preparation. Micro-CT images confirmed obvious dentin-bridge structures in the apigenin-treated specimens compared with the control. Apigenin facilitated the reparative dentin formation through the modulation of inflammation and the activation of signaling regulations. Therefore, apigenin would be a potential therapeutic agent for regenerating dentin in exposed pulp caused by dental caries and traumatic injury.

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.

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