scholarly journals Regional Differences in Viral Growth and Central Nervous System Injury Correlate with Apoptosis

2004 ◽  
Vol 78 (10) ◽  
pp. 5466-5475 ◽  
Author(s):  
Sarah M. Richardson-Burns ◽  
Kenneth L. Tyler
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cortical Neurons ◽  
Fatty Acid Synthase ◽  
Central Nervous System Injury ◽  
Antigenic Variant ◽  
Viral Yield ◽  
Induced Apoptosis ◽  
Restricted Pattern

ABSTRACT Infection of neonatal mice with reovirus T3 Dearing (T3D), the prototypic neurotropic reovirus, causes fatal encephalitis associated with neuronal injury and virus-induced apoptosis throughout the brain. T3D variant K (VarK) is an antigenic variant that has a nearly 1 million-fold reduction in neurovirulence following intracerebral (i.c.) inoculation compared to T3D and a restricted pattern of central nervous system injury with damage limited to the hippocampus, sparing other brain regions. We wished to determine whether the restricted pattern of VarK-induced injury was due to a reduced capacity to replicate in or injure cortical, as opposed to hippocampal, tissue. We found that following i.c. inoculation, VarK grew to similar titers as T3D in the hippocampus but had significantly lower titers in the cortex. Both viruses grew to identical titers and infected the same percentage of cells in mouse primary hippocampal cultures (MHC). In mouse primary cortical cultures (MCC) both the number of infected cells and the viral yield per infected cell were significantly lower for VarK than T3D. VarK-induced apoptosis was limited to the hippocampus in vivo, and in vitro both viruses induced apoptosis equally in MHC but VarK induced significantly less apoptosis than T3D in MCC. Growth of T3D in MCC was reduced to levels comparable to those of VarK following treatment of MCC with caspase inhibitors. Conversely, induction of apoptosis in VarK-infected MCC with fatty acid synthase-activating antibody significantly enhanced viral yield. These results suggest that the decreased neurovirulence of VarK may be due to its failure to efficiently induce apoptosis in cortical neurons.

scholarly journals PTMAc-PEG-PTMAc hydrogel modified by RGDC and hyaluronic acid promotes neural stem cells' survival and differentiation in vitro

RSC Advances ◽  
2017 ◽  
Vol 7 (65) ◽  
pp. 41098-41104 ◽  
Author(s):  
Ruirui Yang ◽  
Caixia Xu ◽  
Tao Wang ◽  
Yuanqi Wang ◽  
Jingnan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Hyaluronic Acid ◽  
Neural Stem Cells ◽  
Biological Properties ◽  
Central Nervous System Injury ◽  
Bioactive Molecules

The enhancement of the biological properties of hydrogels by surface modifying with bioactive molecules is of great significance, especially for the treatment of central nervous system injury by combining engrafted cells.

scholarly journals Oxidative Stress Induces Disruption of the Axon Initial Segment

ASN NEURO ◽  
2017 ◽  
Vol 9 (6) ◽  
pp. 175909141774542 ◽  
Author(s):  
Kareem C. Clark ◽  
Brooke A. Sword ◽  
Jeffrey L. Dupree
Keyword(s):  
Oxidative Stress ◽  
Central Nervous System ◽  
Nervous System ◽  
Cortical Neurons ◽  
Initial Segment ◽  
Reactive Oxygen ◽  
Axon Initial Segment ◽  
Voltage Dependent ◽  
Reversible Loss

The axon initial segment (AIS), the domain responsible for action potential initiation and maintenance of neuronal polarity, is targeted for disruption in a variety of central nervous system pathological insults. Previous work in our laboratory implicates oxidative stress as a potential mediator of structural AIS alterations in two separate mouse models of central nervous system inflammation, as these effects were attenuated following reactive oxygen species scavenging and NADPH oxidase-2 ablation. While these studies suggest a role for oxidative stress in modulation of the AIS, the direct effects of reactive oxygen and nitrogen species (ROS/RNS) on the stability of this domain remain unclear. Here, we demonstrate that oxidative stress, as induced through treatment with 3-morpholinosydnonimine (SIN-1), a spontaneous ROS/RNS generator, drives a reversible loss of AIS protein clustering in primary cortical neurons in vitro. Pharmacological inhibition of both voltage-dependent and intracellular calcium (Ca2+) channels suggests that this mechanism of AIS disruption involves Ca2+ entry specifically through L-type voltage-dependent Ca2+ channels and its release from IP3-gated intracellular stores. Furthermore, ROS/RNS-induced AIS disruption is dependent upon activation of calpain, a Ca2+-activated protease previously shown to drive AIS modulation. Overall, we demonstrate for the first time that oxidative stress, as induced through exogenously applied ROS/RNS, is capable of driving structural alterations in the AIS complex.

scholarly journals Protrudin functions as a scaffold in the endoplasmic reticulum to support axon regeneration in the adult central nervous system

2020 ◽  
Author(s):  
Veselina Petrova ◽  
Craig S. Pearson ◽  
James R. Tribble ◽  
Andrea G. Solano ◽  
Evan Reid ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Endoplasmic Reticulum ◽  
Nervous System ◽  
Cortical Neurons ◽  
Binding Properties ◽  
Adult Central Nervous System ◽  
Low Levels ◽  
Cellular Components

SummaryAdult mammalian central nervous system axons have intrinsically poor regenerative capacity, so axonal injury has permanent consequences. One approach to enhancing regeneration is to increase the axonal supply of growth molecules and organelles. We achieved this by expressing the adaptor molecule Protrudin which is normally found at low levels in non-regenerative neurons. Elevated Protrudin expression enabled robust central nervous system regeneration both in vitro in primary cortical neurons and in vivo in the injured adult optic nerve. Protrudin overexpression facilitated the accumulation of endoplasmic reticulum, integrins and Rab11 endosomes in the distal axon, whilst removing Protrudin’s endoplasmic reticulum localization, kinesin-binding or phosphoinositide-binding properties abrogated the regenerative effects. These results demonstrate that Protrudin promotes regeneration by functioning as a scaffold to link axonal organelles, motors and membranes, establishing important roles for these cellular components in mediating regeneration in the adult central nervous system.

scholarly journals Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Veselina Petrova ◽  
Craig S. Pearson ◽  
Jared Ching ◽  
James R. Tribble ◽  
Andrea G. Solano ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Endoplasmic Reticulum ◽  
Nervous System ◽  
Cortical Neurons ◽  
Binding Properties ◽  
Adaptor Molecule ◽  
Low Levels ◽  
Cellular Components

Abstract Adult mammalian central nervous system axons have intrinsically poor regenerative capacity, so axonal injury has permanent consequences. One approach to enhancing regeneration is to increase the axonal supply of growth molecules and organelles. We achieved this by expressing the adaptor molecule Protrudin which is normally found at low levels in non-regenerative neurons. Elevated Protrudin expression enabled robust central nervous system regeneration both in vitro in primary cortical neurons and in vivo in the injured adult optic nerve. Protrudin overexpression facilitated the accumulation of endoplasmic reticulum, integrins and Rab11 endosomes in the distal axon, whilst removing Protrudin’s endoplasmic reticulum localization, kinesin-binding or phosphoinositide-binding properties abrogated the regenerative effects. These results demonstrate that Protrudin promotes regeneration by functioning as a scaffold to link axonal organelles, motors and membranes, establishing important roles for these cellular components in mediating regeneration in the adult central nervous system.

Brain benzodiazepine levels following intravenous administration of [3H]diazepam: Relationship to the potentiation of purinergic depression of central nervous system neurons

1979 ◽  
Vol 57 (9) ◽  
pp. 1040-1042 ◽  
Author(s):  
Phil Skolnick ◽  
Steven M. Paul ◽  
Paul J. Marangos
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Intravenous Injection ◽  
Cortical Neurons ◽  
Benzodiazepine Receptors ◽  
Time Schedule ◽  
Adenosine Uptake ◽  
Cerebral Cortical Neurons

Levels of [3H] benzodiazepine were measured in rat cerebral cortex following intravenous injection of [3H]diazepam using a dose and time schedule reported to elicit a marked potentiation of the depressant effects of iontophoretically applied 5′-AMP to rat cerebral cortical neurons. The levels of [3H]benzodiazepine obtained strongly suggest (i) that blockade of adenosine uptake as a mechanism for this potentiation is not consistent with the potency of diazepam as an inhibitor of adenosine uptake in vitro, and (ii) that a potentiative interaction of adenosine and diazepam may reflect the binding of these compounds to benzodiazepine receptors.

An in vitro model of the inhibition of axon growth in the lesion scar formed after central nervous system injury

2010 ◽  
Vol 43 (2) ◽  
pp. 177-187 ◽  
Author(s):  
Junko Kimura-Kuroda ◽  
Xichuan Teng ◽  
Yukari Komuta ◽  
Nozomu Yoshioka ◽  
Kazunori Sango ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
In Vitro Model ◽  
Axon Growth ◽  
Central Nervous System Injury ◽  
Vitro Model

Neural Stem Cells to Glial Cells an Important Factor for Brain Injury

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Glial Cells ◽  
Brain Injuries ◽  
The Body ◽  
The Central Nervous System ◽  
Near Future

Stem cells have the capacity to differentiate into any type of cell or organ. Stems cell originate from any part of the body, including the brain. Brain cells or rather neural stem cells have the capacitive advantage of differentiating into the central nervous system leading to the formation of neurons and glial cells. Neural stem cells should have a source by editing DNA, or by mixings chemical enzymes of iPSCs. By this method, a limitless number of neuron stem cells can be obtained. Increase in supply of NSCs help in repairing glial cells which in-turn heal the central nervous system. Generally, brain injuries cause motor and sensory deficits leading to stroke. With all trials from novel therapeutic methods to enhanced rehabilitation time, the economy and quality of life is suppressed. Only PSCs have proven effective for grafting cells into NSCs. Neurons derived from stem cells is the only challenge that limits in-vitro usage in the near future.

scholarly journals Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2104 ◽  
Author(s):  
Eleonora Ficiarà ◽  
Shoeb Anwar Ansari ◽  
Monica Argenziano ◽  
Luigi Cangemi ◽  
Chiara Monge ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Tumors ◽  
Ad Hoc ◽  
Superparamagnetic Iron Oxide ◽  
Conventional Radiotherapy ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.

scholarly journals Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age

2021 ◽  
Vol 22 (4) ◽  
pp. 1725
Author(s):  
Diego Delgado ◽  
Ane Miren Bilbao ◽  
Maider Beitia ◽  
Ane Garate ◽  
Pello Sánchez ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cellular Response ◽  
Platelet Rich Plasma ◽  
Biological Response ◽  
In Vitro Models ◽  
Molecular Composition ◽  
Cellular Models ◽  
The Central Nervous System

Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor’s health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the differences between PRP from young and elderly donors. Two different PRP pools were prepared from donors 65–85 and 20–25 years old. The cellular and molecular composition of both PRPs were analyzed. Subsequently, the cellular response was evaluated in CNS in vitro models, studying proliferation, neurogenesis, synaptogenesis, and inflammation. While no differences in the cellular composition of PRPs were found, the molecular composition of the Young PRP showed lower levels of inflammatory molecules such as CCL-11, as well as the presence of other factors not found in Aged PRP (GDF-11). Although both PRPs had effects in terms of reducing neural progenitor cell apoptosis, stabilizing neuronal synapses, and decreasing inflammation in the microglia, the effect of the Young PRP was more pronounced. In conclusion, the molecular composition of the PRP, conditioned by the age of the donors, affects the magnitude of the biological response.

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