Types of Mammalian Cell Culture Systems and Testing Strategies for Predicting In Vivo Neurotoxicity

Neurotoxicology and its Relation to Developmental Neurotoxicity

Critically Discuss The Major Types Of Mammalian Cell Culture Systems, Together With The Testing Strategies Used To Enhance Their Effectiveness To Predict In Vivo Neurotoxicity.

The understanding that chemical, biochemical and certain physical agents have a negative influence on the organism during their development and progressive maturity is termed as neurotoxicology. Neurotoxicology defines effect by certain chemical products which are directly harmful to the nervous system, such as asbestos, mercury, toxins or ethanol.

Similar to the adult nervous system, the infant nervous system is considered to be more sensitive towards chemical exposure. For many regulatory bodies, roles are needed to be measured as neurotoxicity is a significant health risk goal. Neurotoxicity studies are used to identify possible neurotoxicants contributing to health risks.

Monitoring of Neurotoxicity is often seen as a locational toxicity aspect of the organ; central nervous system (CNS) is one of the initial target body systems. Exposure of pesticide and drug in utero can also have a deleterious effect of the nervous system by the impact of neurotoxic development (Burke et al., 2017). 

The higher vulnerability of the developing brain occurs due to the complex developmental processes of neural progenitor cells, including their commitment and distinction of the proliferation of neuronal and nerve cells; migration, differentiation into the different neuronal and glial subtypes; synaptogenesis; pruneing; myelination; networking and terminal functioning neuronal cells and glial maturation. One difficulty in assessing developmental neurotoxicity (DNT) caused by an exogenous chemical is that it is not only based on the type of exposure (dose, duration) but also on the stage of development of the brain at the time of exposure that occurs during neurodevelopment. Moreover, at least six months after birth, the immature's blood brain barrier (BBB) is not fully formed, thereby enabling a chemical to enter a fetal/neonatal brain.

While research is increasing on the potential toxic properties of nanomaterials, the developmental toxicity field has remained uninvestigated. The embryonic stem cell analysis is an in vitro diagnostic procedure used to examine chemicals ' embryotoxic potential by evaluating their ability to prevent embryonic stem cell differentiation into spontaneously contracting cardiomyocytes. To examine whether nanomaterials are effective enough to inhibit differentiation in the embryonic stem cell process, four well known silica nanoparticles of different sizes were used. Distributions of nanoparticles and dispersion characteristics were determined in the stem cell culture medium, before and during incubation by means of transmission electron microscopy (TEM) and dynamic light scattering (Park  et al., 2009).

Testing Strategies for Neurotoxicity Studies

The first-tier evaluation is designed to test the potential of chemicals in the first steps of a risk-taking cycle for the identification of danger to generate certain neurotoxic effects. The next step is the diagnosis of Neurotoxicities, such as structural or operational disturbance and neuronal impairment degree and location. The study of the quantitative association between the dosage (applied dose) and the target of the toxic behaviors (application) and the dose-to-biological response was conducted during a risk assessment (second phase). The analysis of chemically formed action pathways is the third and final step of neurotoxicity chemistry (Legradi et al., 2018).

Discussion of evidence from studies on neurocognitive animal treatment from low to moderate levels for the identification of prolonged or long-term exposure was noted. Therefore, evaluation of the development of the brain, attention, impulse, motility, fatigue and anxiety effects of the operation was done.

Neurotoxicity control is dependent on in vivo animal testing methodology. The Organization for Economic Cooperation and Development (OECD) holds four test guidelines (TGs) that describe in vivo neurotoxicity studies. Compounds with acute exposure continue, TG 418 requires a single oral administration for hens and is then followed for a period of 21 days. Delayed organophosphorus neurotoxicity is the key speculations which involve hen's behavior, body weight, overall phenotype and microscope. Chemicals provide 28-day daily dose analysis, TG 419, including a 28-day regular oral dosage of organophosphorous toxin for hens of biochemical and histopathological trials. TG 424, a standard oral dosage of rats for immediate, vital or harmful treatment (28 days, 90 days or one year or longer), involving executive tests and histopathological evaluations of nervous tissue systems (Legradi et al., 2018).

The research includes in-vitro methods. Neurotoxicology experiments and research include in-vitro system tests for primary glial and neural tissues in specific areas of the brain; cell line scans for cancers of glial cells or blood tumor, hippocampus monitoring and organotyping of a variety of other cells (Wu et al., 2019).

Toxicity research is under- pressure to meet various alternative demands the regulation of a vast number of common chemicals, where most of them lack adequate toxicity evidence. The analysis of every year's tremendous number of new chemicals and innovative science include nanomaterial science, the evaluation of potentially damaging effects for all critical endpoints and production stages. Therefore it can be concluded, the guidelines by OECD DNT is the best accepted science for evaluating the ability for DNT in public health risk management, and data generated with this protocol are valid and accurate for evaluating these endpoints.

References

Burke, R.D., Todd, S.W., Lumsden, E., Mullins, R.J., Mamczarz, J., Fawcett, W.P., Gullapalli, R.P., Randall, W.R., Pereira, E.F. and Albuquerque, E.X., 2017. Developmental neurotoxicity of the organophosphorus insecticide chlorpyrifos: from clinical findings to preclinical models and potential mechanisms. Journal of neurochemistry, 142, pp.162-177.

Legradi, J.B., Di Paolo, C., Kraak, M.H.S., Van Der Geest, H.G., Schymanski, E.L., Williams, A.J., Dingemans, M.M.L., Massei, R., Brack, W., Cousin, X. and Begout, M.L., 2018. An ecotoxicological view on neurotoxicity assessment. Environmental Sciences Europe, 30(1), p.46.

Park, M.V., Annema, W., Salvati, A., Lesniak, A., Elsaesser, A., Barnes, C., McKerr, G., Howard, C.V., Lynch, I., Dawson, K.A. and Piersma, A.H., 2009. In vitro developmental toxicity test detects inhibition of stem cell differentiation by silica nanoparticles. Toxicology and applied pharmacology, 240(1), pp.108-116.

Wu, L., Zhao, H., Weng, H. and Ma, D., 2019. Lasting effects of general anesthetics on the brain in the young and elderly:“mixed picture” of neurotoxicity, neuroprotection and cognitive impairment. Journal of anesthesia, 33(2), pp.321-335.