scholarly journals Testing methods for the assessment of chemical neurotoxic effects on the developing organisms in pre- and postnatal period

2021 ◽  
Vol 54 (1) ◽  
pp. 41-51
Author(s):  
IO Rashkivska ◽  
NM Nedopytanska ◽  
PG Zhminko ◽  
NО Kornuta ◽  
YaV Kolyanchuk

Aim of the research. Analysis of approaches to the assessment of neurotoxic effects of chemicals during ontogenesis. The dangerous tendency of the increase in the incidence of pathology of the nervous system in the child and the mother, who during pregnancy was exposed to neurotoxicants, necessitates the protection of the child’s body from such a negative effect of chemicals. One of the possible preventive ways to solve this problem is screening of xenobiotics before their widespread application, as well as identification of their ability to cause neurotoxic effects on the body during its development, and banning substances, neurotoxic effects of which on the development of progeny are proven. Materials and Methods. Detection of adverse effects at the stage of foetal development and then at the beginning of the functioning of a nervous system in the postnatal period requires complex experimental studies in laboratory animals, which are described in the recommendations of OECD guideline 426 (OECD Guideline for Testing of Chemicals; Guideline 426: Developmental Neurotoxicity Study, 2007). The OECD guideline 426 protocol provides for a wide range of methods for assessing sensory, motor, behavioural and cognitive functions. Conclusions. Analysis of data given in publications and methodological approaches to research and evaluation of neurotoxic effects of chemicals on the developing organism showed that to obtain representative results it is important to take into account all factors that may affect the result, select adequate informative tests and comply with all requirements. In Ukraine, international methodological approaches to the study of neurotoxic effects of pesticides on the body at the stage of development in the process of ontogenesis are applied at the L.I. Medved’s Research Center of Preventive Toxicology, Food and Chemical Safety, Ministry of Health, Ukraine (State Enterprise), Kyiv, Ukraine. Key Words: nervous system, neurotoxic effects, OECD guideline 426, neurobehavioral tests.

Author(s):  
Steven J. Gill ◽  
Michael H. Nathanson

Anaesthesia induces changes in many organ systems within the body, though clearly none more so than the central nervous system. The physiology of the normal central nervous system is complex and the addition of chronic pathology and polypharmacy creates a significant challenge for the anaesthetist. This chapter demonstrates a common approach for the anaesthetist and specific considerations for a wide range of neurological conditions. Detailed preoperative assessment is essential to gain understanding of the current symptomatology and neurological deficit, including at times restrictions on movement and position. Some conditions may pose challenges relating to communication, capacity, and consent. As part of the consent process, patients may worry that an anaesthetic may aggravate or worsen their neurological disease. There is little evidence to support this understandable concern; however, the risks and benefits must be considered on an individual patient basis. The conduct of anaesthesia may involve a preference for general or regional anaesthesia and requires careful consideration of the pharmacological and physiological impact on the patient and their disease. Interactions between regular medications and anaesthetic drugs are common. Chronically denervated muscle may induce hyperkalaemia after administration of succinylcholine. Other patients may have an altered response to non-depolarizing agents, such as those suffering from myasthenia gravis. The most common neurological condition encountered is epilepsy. This requires consideration of the patient’s antiepileptic drugs, often relating to hepatic enzyme induction or less commonly inhibition and competition for protein binding, and the effect of the anaesthetic technique and drugs on the patient’s seizure risk. Postoperative care may need to take place in a high dependency unit, especially in those with limited preoperative reserve or markers of frailty, and where the gastrointestinal tract has been compromised, alternative routes of drug delivery need to be considered. Overall, patients with chronic neurological conditions require careful assessment and preparation, a considered technique with attention to detail, and often higher levels of care during their immediate postoperative period.


2021 ◽  
Author(s):  
Aml M. Erhuma

The Hypothalamic – Pituitary – Adrenal (HPA) Axis is a unique system that mediates an immediate reactivity to a wide range of stimuli. It has a crucial role in synchronizing the behavioral and hormonal responses to internal and external threats, therefore, increases the chance of survival. It also enables the body systems to adapt to challenges put up by the pregnancy. Since the early stages of pregnancy and throughout delivery, HPA axis of the mother continuously navigates that of the fetus, and both have a specific cross talk even beyond the point of delivery and during postnatal period. Any disturbance in the interaction between the maternal and fetal HPA axes can adversely affect both. The HPA axis is argued to be the mechanism through which maternal stress and other suboptimal conditions during prenatal period can program the fetus for chronic disease in later life. In this chapter, the physiological and non-physiological communications between maternal and fetal HPA axes will be addressed while highlighting specific and unique aspects of this pathway.


2021 ◽  
Vol 17 (2) ◽  
pp. 6-15
Author(s):  
L.A. Dziak ◽  
O.S. Tsurkalenko ◽  
K.V. Chekha ◽  
V.M. Suk

Coronavirus infection is a systemic pathology resulting in impairment of the nervous system. The involvement of the central nervous system in COVID-19 is diverse by clinical manifestations and main mechanisms. The mechanisms of interrelations between SARS-CoV-2 and the nervous system include a direct virus-induced lesion of the central nervous system, inflammatory-mediated impairment, thrombus burden, and impairment caused by hypoxia and homeostasis. Due to the multi-factor mechanisms (viral, immune, hypoxic, hypercoagulation), the SARS-CoV-2 infection can cause a wide range of neurological disorders involving both the central and peripheral nervous system and end organs. Dizziness, headache, altered level of consciousness, acute cerebrovascular diseases, hypogeusia, hyposmia, peripheral neuropathies, sleep disorders, delirium, neuralgia, myalgia are the most common signs. The structural and functional changes in various organs and systems and many neurological symptoms are determined to persist after COVID-19. Regardless of the numerous clinical reports about the neurological and psychiatric symptoms of COVID-19 as before it is difficult to determine if they are associated with the direct or indirect impact of viral infection or they are secondary to hypoxia, sepsis, cytokine reaction, and multiple organ failure. Penetrated the brain, COVID-19 can impact the other organs and systems and the body in general. Given the mechanisms of impairment, the survivors after COVID-19 with the infection penetrated the brain are more susceptible to more serious diseases such as Parkinson’s disease, cognitive decline, multiple sclerosis, and other autoimmune diseases. Given the multi-factor pathogenesis of COVID-19 resulting in long-term persistence of the clinical symptoms due to impaired neuroplasticity and neurogenesis followed by cholinergic deficiency, the usage of Neuroxon® 1000 mg a day with twice-day dosing for 30 days. Also, a long-term follow-up and control over the COVID-19 patients are recommended for the prophylaxis, timely determination, and correction of long-term complications.


2016 ◽  
Author(s):  
Virginie Uhlmann ◽  
Pavan Ramdya ◽  
Ricard Delgado-Gonzalo ◽  
Richard Benton ◽  
Michael Unser

AbstractUnderstanding the biological underpinnings of movement and action requires the development of tools for precise, quantitative, and high-throughput measurements of animal behavior. Drosophila melanogaster provides an ideal model for developing such tools: the fly has unparalleled genetic accessibility and depends on a relatively compact nervous system to generate sophisticated limbed behaviors including walking, reaching, grooming, courtship, and boxing. Here we describe a method that uses active contours to semi-automatically track body and leg segments from video image sequences of unmarked, freely behaving Drosophila. We show that this approach is robust to wide variations in video spatial and temporal resolution and that it can be used to measure leg segment motions during a variety of locomotor and grooming behaviors. FlyLimbTracker, the software implementation of this method, is open-source and our approach is generalizable. This opens up the possibility of tracking leg movements in other species by modifications of underlying active contour models.Author SummaryIn terrestrial animals, including humans, fundamental actions like locomotion and grooming emerge from the displacement of multiple limbs through space. Therefore, precise measurements of limb movements are critical for investigating and, ultimately, understanding the neural basis for behavior. The vinegar fly, Drosophila melanogaster, is an attractive animal model for uncovering general principles about limb control since its genome and nervous system are easy to manipulate. However, existing methods for measuring leg movements in freely behaving Drosophila have significant drawbacks: they require complicated experimental setups and provide limited information about each leg. Here we report a new method - and provide its open-source software implementation, FlyLimbTracker - for tracking the body and leg segments of freely behaving flies using only computational image processing approaches. We illustrate the power of this method by tracking fly limbs during five distinct walking and grooming behaviors and from videos across a wide range of spatial and temporal resolutions. Our approach is generalizable, allowing researchers to use and customize our software for limb tracking in Drosophila and in other species.


A novel magnetic field and radio frequency (1.7 MHz) pulse sequence is described for a whole body n.m.r. imaging machine under construction. Selective excitation is used to obtain signals from successive lines of proton spins (water) across the body to build up an image of a transverse section. The images display spin concentration and spin-lattice relaxation time, T 1 , separately. For a 50 % change in T 1 to be discerned in the human trunk, a spatial resolution of 2 cm 3 is expected for a 2 min scan and 0.5 cm 3 for a 30 min scan. Very preliminary images at the present incomplete stage of development show the geometrical accuracy and T 1 discrimination: an in vivo image demonstrates some of the difficulties to be overcome. In vitro measurements of normal rabbit tissue samples have been made at 24 MHz to map the T 1 distributions that can be expected from normal subjects. The transposition of this information from rabbit to man, and from 24 MHz to 2.5 MHz have been checked and the comparison shown to be meaningful. Of pathological samples, human breast tumour and human liver metastases offer a good contrast to their surrounding tissue, and an experimental investigation has shown that tissue immediately surrounding a tumour also has an elevated T 1 value. A wide range of abnormalities that are associated with abnormal fluid formation in the body may be amenable to imaging by the n.m.r. technique. Potential hazards are believed to be small in the present generation of equipment.


2021 ◽  
Vol 32 (2) ◽  
pp. 120-137
Author(s):  
Firoz Ahmed Quraishi ◽  
Aminur Rahman ◽  
Furial Quraishi Twinkle

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) is causing a worldwide pandemic of COVID-19 within a short span of time. Although patients with COVID-19 primarily present with fever and respiratory illness; a wide range of symptoms involving different systems have been described. While the neurological sequelae of the virus remain poorly understood, there are a growing number of reports of neurological manifestation of COVID-19.The neurological manifestation including both central and peripheral nervous system are increasingly reported in a very subset of COVID-19 patients. The SARS-CoV-2 enters the body mainly via the ACE- 2 receptors within the respiratory system, which causes the body to initiate an immunologic response against potential damage to non-renewable cells. There’s increasing evidence of accumulating that COVID-19, particularly in severe cases, can have neurological consequences although respiratory symptoms nearly always develop before neurological ones. Patients with pre-existing neurological conditions could also be at elevated risk for COVID-19 associated neurological symptoms. The neurological presentations of COVID-19 patients maybe acute and post-acute state. The acute presentations are classified into specific (such as stroke, encephalitis, acute polyneuropathy, etc.) and nonspecific (such as delirium, headache, dizziness, etc.) symptoms with anatomical involvement of either central nervous system including brain or spinal cord, and/or peripheral nervous system, neuromuscular junctions or muscles. Several neurological symptoms have also been demonstrated in post-acute or long covid-19 syndrome. There is a possibility to overlook or misinterpretation of, neurological symptoms in some COVID-19 patients. In infants and young children, the foremost common CNS phenomena are febrile seizures; in adults, non-focal abnormalities will be either neurological or constitutional. To date, neurological manifestations of COVID-19 are described largely within the disease trajectory, and also the long-term effects of such manifestations still remain unexplored and unfolded. This article is intended to review the possible neuro-invasive routes of SARS-CoV-2 and its mechanisms which initiate the neurological damage with neurological presentations of COVID-19 patients. Bangladesh J Medicine July 2021; 32(2) : 120-137


Development ◽  
1990 ◽  
Vol 110 (3) ◽  
pp. 885-896
Author(s):  
P.D. Vize ◽  
A. Vaughan ◽  
P. Krieg

The N-myc proto-oncogene is expressed in a wide range of tissues during mammalian embryogenesis. This observation, along with the oncogenic capacity of this gene, has led to the suggestion that N-myc plays an important role in early development. However, due to the complexity of the expression pattern and the difficulty of manipulating mammalian embryos, little progress has been made towards understanding the developmental function of this gene. To enable a more detailed analysis of the role of this gene in early development, a study of the Xenopus homologue of N-myc was undertaken. Xenopus N-myc cDNA clones were isolated from a neurula library using a murine N-myc probe. Analysis of the timing of expression of N-myc mRNA and of the distribution of N-myc protein during Xenopus development indicate that this gene may be playing an important role in the formation of a number of embryonic structures, including the nervous system. N-myc is initially expressed as a maternal RNA, but this mRNA is degraded by the gastrula stage of development. Zygotic expression does not commence until late neurula. Examination of the distribution of the N-myc protein by whole-mount immunohistochemistry indicates that the early embryonic expression occurs in the central nervous system, the neural crest, the somites and the epidermis. Later expression is mostly within the head and somites. Specific structures within the head that express the protein include the eye, otic vesicle, fore and hindbrain and a number of cranial nerves. The results demonstrate that while N-myc is expressed in the developing nervous system of Xenopus, the timing of expression indicates that it is unlikely to be involved in regulation of the very first stages of neurogenesis.


2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Bo Wang ◽  
Yanli Du

Cadmium (Cd) is a heavy metal that has received considerable concern environmentally and occupationally. Cd has a long biological half-life mainly due to its low rate of excretion from the body. Thus, prolonged exposure to Cd will cause toxic effect due to its accumulation over time in a variety of tissues, including kidneys, liver, central nervous system (CNS), and peripheral neuronal systems. Cd can be uptaken from the nasal mucosa or olfactory pathways into the peripheral and central neurons; for the latter, Cd can increase the blood brain barrier (BBB) permeability. However, mechanisms underlying Cd neurotoxicity remain not completely understood. Effect of Cd neurotransmitter, oxidative damage, interaction with other metals such as cobalt and zinc, estrogen-like, effect and epigenetic modification may all be the underlying mechanisms. Here, we review thein vitroandin vivoevidence of neurotoxic effects of Cd. The available finding indicates the neurotoxic effects of Cd that was associated with both biochemical changes of the cell and functional changes of central nervous system, suggesting that neurotoxic effects may play a role in the systemic toxic effects of the exposure to Cd, particularly the long-term exposure.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Nasrin Hosseini ◽  
Shabnam Nadjafi ◽  
Behnaz Ashtary

Abstract The sudden and storming onset of coronavirus 2 infection (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) was associated by severe acute respiratory syndrome. Recently, corona virus disease 19 (COVID-19) has appeared as a pandemic throughout the world. The mutational nature of the virus, along with the different means of entering and spreading throughout the body has involved different organs. Thus, patients are faced with a wide range of symptoms and signs. Neurological symptoms, such as anosmia, agnosia, stroke, paralysis, cranial nerve deficits, encephalopathy, meningitis, delirium and seizures, are reported as common complications affecting the course of the disease and its treatment. In this review, special attention was paid to reports that addressed the acute or chronic neurological manifestations in COVID-19 patients who may present acute respiratory syndrome or not. Moreover, we discussed the central (CNS) and peripheral nervous system (PNS) complications in SARS-Cov2-infected patients, and also the pathophysiology of neurological abnormalities in COVID-19.


Author(s):  
Wiktor Djaczenko ◽  
Carmen Calenda Cimmino

The simplicity of the developing nervous system of oligochaetes makes of it an excellent model for the study of the relationships between glia and neurons. In the present communication we describe the relationships between glia and neurons in the early periods of post-embryonic development in some species of oligochaetes.Tubifex tubifex (Mull. ) and Octolasium complanatum (Dugès) specimens starting from 0. 3 mm of body length were collected from laboratory cultures divided into three groups each group fixed separately by one of the following methods: (a) 4% glutaraldehyde and 1% acrolein fixation followed by osmium tetroxide, (b) TAPO technique, (c) ruthenium red method.Our observations concern the early period of the postembryonic development of the nervous system in oligochaetes. During this period neurons occupy fixed positions in the body the only observable change being the increase in volume of their perikaryons. Perikaryons of glial cells were located at some distance from neurons. Long cytoplasmic processes of glial cells tended to approach the neurons. The superimposed contours of glial cell processes designed from electron micrographs, taken at the same magnification, typical for five successive growth stages of the nervous system of Octolasium complanatum are shown in Fig. 1. Neuron is designed symbolically to facilitate the understanding of the kinetics of the growth process.


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