scholarly journals The Future of Neurotoxicology: A Neuroelectrophysiological Viewpoint

2021 ◽  
Vol 3 ◽  
Author(s):  
David W. Herr
Keyword(s):  
Nervous System ◽  
Predictive Accuracy ◽  
Critical Role ◽  
Sensory Perception ◽  
Clinical Applications ◽  
Adverse Outcomes ◽  
Human Populations ◽  
Predictive Toxicology ◽  
The Brain

Neuroelectrophysiology is an old science, dating to the 18th century when electrical activity in nerves was discovered. Such discoveries have led to a variety of neurophysiological techniques, ranging from basic neuroscience to clinical applications. These clinical applications allow assessment of complex neurological functions such as (but not limited to) sensory perception (vision, hearing, somatosensory function), and muscle function. The ability to use similar techniques in both humans and animal models increases the ability to perform mechanistic research to investigate neurological problems. Good animal to human homology of many neurophysiological systems facilitates interpretation of data to provide cause-effect linkages to epidemiological findings. Mechanistic cellular research to screen for toxicity often includes gaps between cellular and whole animal/person neurophysiological changes, preventing understanding of the complete function of the nervous system. Building Adverse Outcome Pathways (AOPs) will allow us to begin to identify brain regions, timelines, neurotransmitters, etc. that may be Key Events (KE) in the Adverse Outcomes (AO). This requires an integrated strategy, from in vitro to in vivo (and hypothesis generation, testing, revision). Scientists need to determine intermediate levels of nervous system organization that are related to an AO and work both upstream and downstream using mechanistic approaches. Possibly more than any other organ, the brain will require networks of pathways/AOPs to allow sufficient predictive accuracy. Advancements in neurobiological techniques should be incorporated into these AOP-base neurotoxicological assessments, including interactions between many regions of the brain simultaneously. Coupled with advancements in optogenetic manipulation, complex functions of the nervous system (such as acquisition, attention, sensory perception, etc.) can be examined in real time. The integration of neurophysiological changes with changes in gene/protein expression can begin to provide the mechanistic underpinnings for biological changes. Establishment of linkages between changes in cellular physiology and those at the level of the AO will allow construction of biological pathways (AOPs) and allow development of higher throughput assays to test for changes to critical physiological circuits. To allow mechanistic/predictive toxicology of the nervous system to be protective of human populations, neuroelectrophysiology has a critical role in our 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.

Environmental exposures impact the nervous system in a life stage-specific manner

Neuroforum ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Julia Tigges ◽  
Tamara Schikowski ◽  
Ellen Fritsche
Keyword(s):  
Nervous System ◽  
Life Stage ◽  
Environmental Pollutants ◽  
Toxicity Assessment ◽  
Test Methods ◽  
Adverse Outcomes ◽  
Assessment Process ◽  
Health Concern ◽  
Adverse Health Effects

Abstract Exposure to environmental pollutants like chemicals or air pollution is major health concern for the human population. Especially the nervous system is a sensitive target for environmental toxins with exposures leading to life stage-dependent neurotoxicity. Developmental and adult neurotoxicity are characterized by specific adverse outcomes ranging from neurodevelopmental disorders to neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. The risk assessment process for human health protection is currently undergoing a paradigm change toward new approach methods that allow mechanism-based toxicity assessment. As a flagship project, an in vitro battery of test methods for developmental neurotoxicity evaluation is currently supported by the Organization for Economic Co-operation and Development (OECD). A plethora of stem cell-based methods including brain spheres and organoids are currently further developed to achieve time- and cost-saving tools for linking MoA-based hazards to adverse health effects observed in humans.

Understanding the Physiology of the Blood-Brain Barrier: In Vitro Models

Physiology ◽  
1998 ◽  
Vol 13 (6) ◽  
pp. 287-293 ◽  
Author(s):  
Gerald A. Grant ◽  
N. Joan Abbott ◽  
Damir Janigro
Keyword(s):  
Central Nervous System ◽  
Tissue Culture ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Blood Brain ◽  
Brain Tissue Culture ◽  
The Brain

Endothelial cells exposed to inductive central nervous system factors differentiate into a blood-brain barrier phenotype. The blood-brain barrier frequently obstructs the passage of chemotherapeutics into the brain. Tissue culture systems have been developed to reproduce key properties of the intact blood-brain barrier and to allow for testing of mechanisms of transendothelial drug permeation.

Kirlian Experimental Analysis and IoT

2021 ◽  
Vol 10 (2) ◽  
pp. 29-43
Author(s):  
Rohit Rastogi ◽  
Mamta Saxena ◽  
Devendra K. Chaturvedi ◽  
Mayank Gupta ◽  
Akshit Rajan Rastogi ◽  
...  
Keyword(s):  
Nervous System ◽  
Energy Levels ◽  
Critical Role ◽  
The Body ◽  
Extensive Literature ◽  
Entire Body ◽  
Body Parts ◽  
Sodium Potassium ◽  
Charged Ions ◽  
The Brain

Our entire body, including the brain and nervous system, works with the help of various kinds of biological stuff which includes positively charged ions of elements like sodium, potassium, and calcium. The different body parts have different energy levels, and by measuring the energy level, we can also measure the fitness of an individual. Moreover, this energy and fitness are directly related to mental health and the signals being transmitted between the brain and other parts of the body. Various activities like walking, talking, eating, and thinking are performed with the help of these transmission signals. Another critical role played by them is that it helps in examining the mechanisms of cells present at various places in the human body and signaling the nervous system and brain if they are properly functioning or not. This manuscript is divided into two parts where, in the first part, it provides the introduction, background, and extensive literature survey on Kirlian experiments to measure the human's organ energy.

scholarly journals Computational toxicology

2015 ◽  
Vol 34 (12) ◽  
pp. 1304-1309 ◽  
Author(s):  
RT Naven ◽  
S Louise-May
Keyword(s):  
Critical Role ◽  
Pharmaceutical Research ◽  
In Vitro Models ◽  
New Drugs ◽  
Data Sets ◽  
Predictive Toxicology ◽  
Drug Induced ◽  
Chemical Toxicology

Predictive toxicology plays a critical role in reducing the failure rate of new drugs in pharmaceutical research and development. Despite recent gains in our understanding of drug-induced toxicity, however, it is urgent that the utility and limitations of our current predictive tools be determined in order to identify gaps in our understanding of mechanistic and chemical toxicology. Using recently published computational regression analyses of in vitro and in vivo toxicology data, it will be demonstrated that significant gaps remain in early safety screening paradigms. More strategic analyses of these data sets will allow for a better understanding of their domain of applicability and help identify those compounds that cause significant in vivo toxicity but which are currently mis-predicted by in silico and in vitro models. These ‘outliers’ and falsely predicted compounds are metaphorical lighthouses that shine light on existing toxicological knowledge gaps, and it is essential that these compounds are investigated if attrition is to be reduced significantly in the future. As such, the modern computational toxicologist is more productively engaged in understanding these gaps and driving investigative toxicology towards addressing them.

scholarly journals LATENT HERPES SIMPLEX VIRUS IN THE CENTRAL NERVOUS SYSTEM OF RABBITS AND MICE

1973 ◽  
Vol 138 (3) ◽  
pp. 740-744 ◽  
Author(s):  
F. B. Knotts ◽  
M. L. Cook ◽  
J. G. Stevens
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Organ Cultures ◽  
The Central Nervous System ◽  
Simplex Virus ◽  
The Brain

Herpes simplex virus (HSV) type 1 induces a long-standing latent infection in the central nervous system of mice and rabbits. The infection was extablished in the brain stems of rabbits after corneal inoculation of the virus, and in the spinal cords of mice after rear footpad infection. In these animals, infectious virus could not be recovered by direct isolation from tissues; it was detected only after the tissues were maintained as organ cultures in vitro.

scholarly journals Drug Penetration into the Central Nervous System: Pharmacokinetic Concepts and In Vitro Model Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1542
Author(s):  
Felix Neumaier ◽  
Boris D. Zlatopolskiy ◽  
Bernd Neumaier
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Model Systems ◽  
Pharmacokinetic Parameters ◽  
Special Focus ◽  
Drug Penetration ◽  
The Central Nervous System ◽  
The Brain

Delivery of most drugs into the central nervous system (CNS) is restricted by the blood–brain barrier (BBB), which remains a significant bottleneck for development of novel CNS-targeted therapeutics or molecular tracers for neuroimaging. Consistent failure to reliably predict drug efficiency based on single measures for the rate or extent of brain penetration has led to the emergence of a more holistic framework that integrates data from various in vivo, in situ and in vitro assays to obtain a comprehensive description of drug delivery to and distribution within the brain. Coupled with ongoing development of suitable in vitro BBB models, this integrated approach promises to reduce the incidence of costly late-stage failures in CNS drug development, and could help to overcome some of the technical, economic and ethical issues associated with in vivo studies in animal models. Here, we provide an overview of BBB structure and function in vivo, and a summary of the pharmacokinetic parameters that can be used to determine and predict the rate and extent of drug penetration into the brain. We also review different in vitro models with regard to their inherent shortcomings and potential usefulness for development of fast-acting drugs or neurotracers labeled with short-lived radionuclides. In this regard, a special focus has been set on those systems that are sufficiently well established to be used in laboratories without significant bioengineering expertise.

scholarly journals Glymphatics: A Transformative Development in Medical Neuroscience Relevant to Injuries in Military Central Nervous System

2021 ◽  
Author(s):  
James Meyerhoff ◽  
Nabarun Chakraborty ◽  
Rasha Hammamieh
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Sleep Deprivation ◽  
Brain Edema ◽  
Critical Role ◽  
Spatial Relationship ◽  
Military Operations ◽  
Glymphatic System ◽  
The Brain

ABSTRACT Introduction The glia-operated glymphatic system, analogous to but separate from the lymphatics in the periphery, is unique to brain and retina, where it is very closely aligned with the arteriolar system. This intimate relationship leads to a “blood vessel like” distribution pattern of glymphatic vessels in the brain. The spatial relationship of glymphatics, including their essential component aquaporin-4 with vascular pericytes of brain arterioles is critical to functionality and is termed “polarization”. Materials and Methods We review the available literature on the factors affecting the resting state of glymphatics under normal conditions, including the important role of sleep in supporting normal glymphatic function (including waste removal) as well as the critical role of “polarization” under normal conditions. We then examine the effects of traumatic brain injury (TBI) or seizures on the glymphatic system and its state of “polarization”. Results Injury, such as TBI, can disrupt polarization resulting in “depolarization” leading to brain edema. Conclusion Damage to the glymphatic system might explain the brain edema so often seen following TBI or other insult. Moreover, similar damage should be expected in response to seizures, which can often be associated with chemical exposures as well as with TBI. Military operations, whether night operations or continuous operations, quite often impose limitations on sleep. As glymphatic function is sleep-dependent, sleep deprivation alone could compromise glymphatic function, as well, and might in addition, explain some of the well-known performance deficits associated with sleep deprivation. Possible effects of submarine and diving operations, chemical agents (including seizures), as well as high altitude exposure and other threats should be considered. In addition to the brain, the retina is also served and protected by the glymphatic system. Accordingly, the effect of military-related risks (e.g., exposure to laser or other threats) to retinal glymphatic function should also be considered. An intact glymphatic system is absolutely essential to support normal central nervous system functionality, including cognition. This effects a broad range of military threats on brain and retinal glymphatics should be explored. Possible preventive and therapeutic measures should be proposed and evaluated, as well.

Astroglial contribution to tau-dependent neurodegeneration

2019 ◽  
Vol 476 (22) ◽  
pp. 3493-3504 ◽  
Author(s):  
Marta Sidoryk-Węgrzynowicz ◽  
Lidia Strużyńska
Keyword(s):  
Nervous System ◽  
Synaptic Transmission ◽  
Neurofibrillary Tangles ◽  
Neuronal Survival ◽  
Critical Role ◽  
Proper Function ◽  
Neuronal Dysfunction ◽  
Neuronal Function ◽  
Glutamate Homeostasis ◽  
The Brain

Astrocytes, by maintaining an optimal environment for neuronal function, play a critical role in proper function of mammalian nervous system. They regulate synaptic transmission and plasticity and protect neurons against toxic insults. Astrocytes and neurons interact actively via glutamine-glutamate cycle (GGC) that supports neuronal metabolic demands and neurotransmission. GGC deficiency may be involved in different diseases of the brain, where impaired astrocytic control of glutamate homeostasis contributes to neuronal dysfunction. This includes tau-dependent neurodegeneration, where astrocytes lose key molecules involved in regulation of glutamate/glutamine homeostasis, neuronal survival and synaptogenesis. Astrocytic dysfunction in tauopathy appears to precede neurodegeneration and overt tau neuropathology such as phosphorylation, aggregation and formation of neurofibrillary tangles. In this review, we summarize recent studies demonstrating that activation of astrocytes is strictly associated with neurodegenerative processes including those involved in tau related pathology. We propose that astrocytic dysfunction, by disrupting the proper neuron-glia signalling early in the disease, significantly contributes to tauopathy pathogenesis.

Biochemistry

1936 ◽  
Vol 82 (339) ◽  
pp. 431-433
Author(s):  
J. H. Quastel
Keyword(s):  
Nervous System ◽  
Brain Tissue ◽  
Brain Slice ◽  
Brain Slices ◽  
Ringer Solution ◽  
Living Animal ◽  
Dominant Form ◽  
Straight Line ◽  
The Brain

I want to speak of the work we have been doing in Cardiff on the metabolism of the nervous system. The work was carried out there because of the importance of the narcosis treatment. It seemed to us there a pity that a treatment such as that should be given up because of the considerable toxicity possible in relation to it. The research was undertaken to see if we could diminish the toxicity, at the same time seeking an idea as to how narcotics work. I ask that you will realize that the main substance burned by the brain is glucose. The dominant form of metabolism in the nervous system is connected with the breakdown of glucose and lactic acid, and this can be proved by experiment in the living animal and with brain-tissue in vitro. In doing experiments we are not able to carry out work with human brain, because we cannot get human tissue fresh enough, so we have to carry out experiments with animals. They are carried out in this way. We cut slices of the cortex of the brain as soon as the animal is dead, that is to say, within ten minutes of death the brain is out and slices have been cut. They are placed in a physiological medium in the presence of glucose, and we follow the metabolism of that tissue, which allows us to estimate the amount of oxygen being taken up by the brain. If luminal, chloretone, hyoscine or somnifaine be placed with the brain-tissue, then the respiration, instead of being at the usual level, starts lower down, and maintains a straight line. We wanted to see whether this action is reversible or irreversible. If the latter, then on removing the brain-slices from the narcotic it should no longer behave like a normal piece of tissue. Actually, when the brain-slice is removed and placed in Ringer solution, with no narcotic, the respiration goes up and becomes equal to that shown by the slice which had no narcotic. That is to say, the process is reversible.

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