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The tripeptide glutathione (γ-glutamylcysteinylglycine; GSH) is the most abundant antioxidant thiol in the brain. GSH plays a critical role in protecting brain cells from oxidative stress and xenobiotics, as well as maintaining the thiol redox state. High levels of GSH are present in the ce ...

Oxidative stress results from an imbalance between production of reactive oxygen and nitrogen species (ROS and RNS, respectively) and endogenous antioxidant defense mechanisms. Increased generation of ROS/RNS is implicated in the pathogenesis of a variety of human diseases, inc ...

Nitric oxide (NO) is a free radical molecule with a short half-life (

Astrocytes, the most abundant cell type in the brain, proliferate during brain development. While it is generally accepted that mature astrocytes do not proliferate, neural stem cells, which have characteristics of astrocytes, retain the ability of self-renewal. Furthermore, astr ...

In vitro test methods can provide a rapid approach for the screening of large numbers of chemicals for their potential to produce toxicity. In order to identify potential developmental neurotoxicants, assessment of critical neurodevelopmental processes, such as neuronal differ ...

Cell signaling is a complex process which controls basic cellular activities and coordinates actions to �maintain normal cellular homeostasis. Alterations in signaling processes have been associated with �neurological diseases, such as Alzheimer’s and cerebellar ataxia, as ...

There is a growing concern about the effects of chemicals on the developing nervous system. Chemical exposure at critical periods of development can be associated with effects ranging from subtle to profound on the structure and/or function of the nervous system. Understanding critical ...

Parkinson’s disease (PD) is the second most common neurodegenerative diseases, which occurs in both inheritable and sporadic forms. The interplay of the genetic mutations and environmental exposure to disease risk factors contributes to the pathogenic events leading to the demise of ...

Investigation of mechanisms responsible for dopaminergic neuron death is critical for understanding the pathogenesis of Parkinson’s disease, yet this is often quite challenging technically. Here, we describe detailed methods for culturing primary mesencephalic dopamin ...

The ability to quantify changes of synaptic structure, whether associated with the formation of synapse in early development or the degeneration of synapses in adult life in an in vitro culture system, is important for understanding the underlying mechanisms. Astrocytes play a vital role ...

Damage to the central nervous system (CNS) is selective, likely reflecting the intrinsic properties of �individual cell types. Targets of chemical injury are diverse hence assessing neurotoxicity is extremely difficult. Overcoming this obstacle requires a general screen or “mar ...

Serum-free aggregating brain cell cultures are free-floating three-dimensional primary cell cultures able to reconstitute spontaneously a histotypic brain architecture to reproduce critical steps of brain development and to reach a high level of structural and functional m ...

The developing nervous system is particularly susceptible to toxicants, and exposure during development may result in long-lasting neurological impairments. The damage can range from subtle to severe, and it may impose substantial burdens on affected individuals, their famili ...

Microglial cells are the resident immune cells of the central nervous system. Progress in the recent decade has clearly established that microglial cells participate or even actively drive neurological disease. Much of our current knowledge has been generated by investigating micr ...

Molecular chaperones assist the folding of nascent proteins during translation into their correct conformations. Neurotoxic metals such as copper (Cu) and lead (Pb) may produce a deficiency in chaperone function that compromises protein secretion and exacerbates protein aggr ...

Primary neuronal cultures and neuronal cell lines derived from rodents are widely used to study basic physiological properties of neurons, and represent a useful tool to study the potential neurotoxicity of chemicals. While short-term culturing of neurons can be a very straightforwa ...

The blood brain barrier regulates the transport of chemicals from entering and leaving the brain. Brain capillaries establish the barrier and restrict transport into the brain by providing a physical and chemical barrier. The physical barrier is due to tight membrane junctions separat ...

This introductory Chapter provides a brief overview of the field of neurotoxicology and of the role played by in vitro approaches in investigations on mechanisms of neurotoxicity and of developmental neurotoxicity, and in providing suitable models for neurotoxicity screening.

Developmental neurotoxicity (DNT) of environmental chemicals is a serious threat to human health. So far, DNT testing is performed in animals. Such in vivo testing is time-consuming, expensive, and uses large numbers of animals. Moreover, species differences (rat–human) bear the probl ...

Glia-neuron sandwich cocultures are “in vitro” cell systems suitable to evaluate cell-to-cell interactions relaying on the release of soluble factors, such as proinflammatory cytokines. This chapter presents a protocol to obtain a sandwich coculture from primary rat glial cells and ...