Classification of advanced methods for evaluating neurotoxicity

Han, Kwan Hee; Woo, Dong Ho

doi:10.1007/s13273-021-00161-6

Cited by 3 publications

(1 citation statement)

References 84 publications

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“…Brains affected by neurodegenerative diseases have elevated levels of pro-inflammatory cytokines [ 6 ]. In addition, LPS-treated mice display increased neuronal death and impaired synaptic plasticity [ 7 , 8 ], suggesting that the regulation of LPS-induced neuroinflammation could be important in providing a potential strategy to reduce or prevent the development of neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of Bcl-2 on Lipopolysaccharide-Induced Neuroinflammation in Cortical Neural Stem Cells

Park

Han

2022

IJMS

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Neuroinflammation is involved in the pathogenesis of neurodegenerative diseases due to increased levels of pro-inflammatory cytokines in the central nervous system (CNS). Chronic neuroinflammation induced by neurotoxic molecules accelerates neuronal damage. B-cell lymphoma 2 (Bcl-2) is generally accepted to be an important anti-apoptotic factor. However, the role of Bcl-2 in neuroprotection against neuroinflammation remains to be determined. The purpose of this study was to investigate the neuroprotective effect of Bcl-2 on lipopolysaccharide (LPS)-induced neuroinflammation in cortical neural stem cells (NSCs). LPS decreased mRNA and protein levels of Tuj-1, a neuron marker, and also suppressed neurite outgrowth, indicating that LPS results in inhibition of neuronal differentiation of NSCs. Furthermore, LPS treatment inhibited Bcl-2 expression during neuronal differentiation; inhibition of neuronal differentiation by LPS was rescued by Bcl-2 overexpression. LPS-induced pro-inflammatory cytokines, including interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α), were decreased by Bcl-2 overexpression. Conversely, Bcl-2 siRNA increased the LPS-induced levels of IL-6 and TNF-α, and decreased neuronal differentiation of NSCs, raising the possibility that Bcl-2 mediates neuronal differentiation by inhibiting the LPS-induced inflammatory response in NSC. These results suggest that Bcl-2 has a neuroprotective effect by inhibiting the LPS-induced inflammatory response in NSCs.

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Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of Bcl-2 on Lipopolysaccharide-Induced Neuroinflammation in Cortical Neural Stem Cells

Park

Han

2022

IJMS

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Cross-conjugated polymers as fluorescent probes for intracellular potassium ion detection

Wang

Pan

Shen

et al. 2023

Sensors and Actuators B: Chemical

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Practical Aspects of Assessing Toxic Lesions of the Peripheral Nervous System in Preclinical Studies in Rodents: A Review

Ilinskii,

Tyunin,

Chepur

et al. 2024

Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo pr

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INTRODUCTION. In the current practice of preclinical safety studies of pharmacologically active substances, standard neurotoxicity assessment procedures are mainly aimed at diagnosing higher nervous activity and behavioural disorders. However, it is the structures of the peripheral nervous system that are particularly susceptible to drug-induced neurotoxicity, which renders these structures an easy target and leads to a high incidence of neurotoxic side effects. These circumstances dictate the importance of refining methodological approaches to the assessment of toxic injury in the peripheral nervous system.AIM. The study aimed to analyse the current methodological level of clinical and functional tests for assessing the toxic effects of pharmacologically active substances on the structures of the peripheral nervous system, as well as to formulate practical recommendations for using these tests in preclinical studies in rodents.DISCUSSION. Rodents are considered the optimal test system for preclinical studies of pharmacologically active substances, but it is impossible to reproduce the entire neurological examination that is conducted to identify clinical equivalents of neurotoxicity in humans using these animals. This article presents a systematic approach to using available diagnostic tests to increase the translatability of data. The article briefly describes the neurological deficits due to adverse drug reactions in humans, as well as the main toxidromes that can also occur in animals. Based on a literature review and experience, the authors provide practical recommendations for performing basic tests to study the strength and tone of muscles, the state of physiological reflexes, the coordination of movements, and various types of sensitivities in rodents. The article provides a brief overview of the diagnostic utility of electrophysiological testing for identifying toxic damage to the peripheral nervous system. The following tests are recommended as a minimum list of primary screening techniques for detecting neurotoxic side effects in study animals: a resting posture assessment, the beam walking test, the horizontal bar test, the digit abduction score assay, the tail flick test, and the Preyer reflex test.CONCLUSIONS. The results of a comprehensive assessment of neurological deficits in rodent experiments should be analysed from a clinically relevant perspective— that is, with a focus on topical diagnosis and common pathological process components. It is advisable to verify the pathological process at the level of the peripheral nervous system using a set of electrophysiological techniques.

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Classification of advanced methods for evaluating neurotoxicity

Cited by 3 publications

References 84 publications

Neuroprotective Effect of Bcl-2 on Lipopolysaccharide-Induced Neuroinflammation in Cortical Neural Stem Cells

Neuroprotective Effect of Bcl-2 on Lipopolysaccharide-Induced Neuroinflammation in Cortical Neural Stem Cells

Cross-conjugated polymers as fluorescent probes for intracellular potassium ion detection

Practical Aspects of Assessing Toxic Lesions of the Peripheral Nervous System in Preclinical Studies in Rodents: A Review

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