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Radiotracer Labeling of Brain Slices
Published in Avital Schurr, Benjamin M. Rigor, BRAIN SLICES in BASIC and CLINICAL RESEARCH, 2020
George C. Newman, Frank E. Hospod, Clifford S. Patlak, Hui Qi
A primary motivation for using brain slices is the ease of selectively altering the extracellular environment of the tissue. A large number of studies have utilized this advantage to model ischemia by reducing buffer pO2 and/or glucose. Two particularly systematic studies illustrate the value of this approach. In the first, hippocampal slices were exposed to various levels of low glucose and low pO2 and then synaptic activity was checked by orthodromic stimulation 30 min after return to standard conditions. It was possible to establish a 50% inhibitory dose for pO2 and glucose as a means of screening antihypoxic/anti-ischemic drugs.14 An advantage of this approach is that it is possible to create specific degrees of energy impairment, as shown by recent results from our laboratory (Figure 4). Thus, functional impairment of particular energy-dependent processes, such as tissue Ca++ accumulation, can be studied under defined energy states. A second valuable approach to brain slice ischemia employs transient anoxia/aglycemia as a model of transient global ischemia.15 This permits detailed study of the time course of energy metabolites during and after transient energy impairment.
Convulsant-Induced Neocortical Epilepsy
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
Allen B. Chatt, John S. Ebersole
For more than 20 years there has been considerable effort directed at characterizing, and postulating the origin of the burst discharges (paroxysmal depolarization shifts, PDS) that can be recorded from neurons exposed to convulsant agents.40 Recently there has been much work with in vitro investigations using brain slice preparations or isolated cells in culture. Such experiments have provided important information about the physiology of individual cells and the synaptic, membrane, and ionic bases of neuronal bursting (for review see Chapter 5 and Ref. 41,42). Accompanying the data from these basic models, however, is an uncertainty about the operational significance of the observed phenomena for epilepsy within intact brain. Further, little attention has been paid to the heterogeneous nature of cells constituting the neocortex, with results from one cell group being generalized to all cell groups. The normal local circuit or more distant neuronal interactions that are essential for clinical epilepsy cannot be assured in the reduced cell population of a slice, where nearly every neuron is partially deafferented, axotomized, and dendrectomized, or in a cell culture where normal cortical networks are totally absent. Consequently, the clinical relevance of results obtained from these models, though interesting, cannot be assured.
Determination of Toxicity
Published in David Woolley, Adam Woolley, Practical Toxicology, 2017
The nervous system, from the central nervous system or peripheral nervous system, presents more of a problem, given that its principal function is to transmit electrical impulses or transfer small amounts of quickly decaying chemicals at synapses between neurons or other receptors such as those on muscles. Some of the endpoints are the same as those for other single-cell systems, such as cytotoxicity, apoptosis, and proliferation. More specific endpoints include electrophysiological aspects such as ion channels, and enzyme studies can include acetyl cholinesterase and other markers of effect. Techniques such as patch-clamp electrophysiology and calcium imaging allow the user to understand, respectively, how single cells and groups of cells behave in response to certain stimuli. Advances in microscopy have allowed insight into how nervous tissues respond to electric fields. These cells may not necessarily represent the complex network of nervous tissue but give understanding into how single or groups of cells respond. Such methods tend to rely on primary cell cultures taken from animals, and although they may be three Rs compliant, animal use could still be high. On a larger scale, the brain is suitable for study in tissue slice preparations, and it is possible to isolate the various cell types for individual study. The drawback of these techniques, however, is that change in one aspect of this complex system does not necessarily directly correlate with effects in life. Brain slices can be studied with techniques such as electrophysiology, autoradiography, genetic analysis, and histopathological staining. They allow intact nervous systems to be investigated and experimented upon.
Regulation of LTP at rat hippocampal Schaffer-CA1 in vitro by musical rhythmic magnetic fields generated by red-pink (soothing) music tracks
Published in International Journal of Radiation Biology, 2023
Zijia Jin, Lei Dong, Lei Tian, Mei Zhou, Yu Zheng
SD rats were anesthetized with chloral hydrate at a concentration of 0.1 ml/20 g (10%), and their brains were quickly removed after decapitation and stored at 4 °C in a cutting solution with the following composition (in mM): sucrose 90, NaCl 87.2, KCl 2.5, MgCl2 7, CaCl2 0.5, NaH2PO4 1.25, NaHCO3 25, and glucose 16.7. Brain slices were sectioned using a vibrating tissue slicer VF-200 (Precision, Natick, MA) with a thickness of 400 μm per slice. During the process of cutting, the cutting solution was continuously perfused with a mixture of 95% O2/5%CO2 for 5–10 min. Brain slices were subsequently incubated in artificial cerebrospinal fluid (ACSF) for 1 h at a temperature of 33 °C. Composition (in mM): NaCl 120, KCl 2.5, MgSO4•7H2O 2, CaCl2 2, NaH2PO4•2H2O 1.25, NaHCO3 26 and glucose 10. All reagents were of analytical grade (Tianjin Fengchuan Chemical Reagent Technology Company). All brain sections were randomly assigned to either control or experimental groups.
Recent advances in cellular models for discovering prion disease therapeutics
Published in Expert Opinion on Drug Discovery, 2022
Lea Nikolić, Chiara Ferracin, Giuseppe Legname
In summary, organotypic brain slice cultures (BSCs) discussed here are produced from genetically identical animals permitting tight control of genetic background variations when different parameters of disease-modifying drugs are assessed. As a large number of brain slices can be prepared from a single animal, this tool substantially reduces the number of prion-infected animals used for preclinical anti-prion drug development. BSCs are time- and cost-effective tools that allow for stringent, rapid, and sensitive evaluation of potential anti-prion therapeutics when coupled with RT-QuIC assay [78]. Additionally, cultured organotypic sections are amenable for chemical or genetic manipulations [79,80]. On the other hand, there are several drawbacks to the use of organotypic brain slices. As they do not contain functional capillaries, compounds are screened in the absence of blood-brain barrier (BBB) [81]. In this regard, a pioneering work done by Duport et al., in 1998, showed that brain capillary endothelial cells can be co-cultured with BSCs [82]. However, although this co-culture system holds the potential to cast new light on studying drug permeability and drug delivery, it still needs to be substantially refined to reach its widespread use in pharmacological studies. Alternatively, BSCs can also be produced from postmortem or resected tissue of an adult human brain [83]. Even if there are no published studies on human brain sections in the prion field, it can easily be envisioned how this model could contribute to our better understanding of prion diseases and yield more relevant therapeutics for clinical studies.
Comparison of ELF-EMFs stimulation with current stimulation on the regulation of LTP of SC-CA1 synapses in young rat hippocampus
Published in International Journal of Radiation Biology, 2021
Yu Zheng, Wenjun Zhao, Xiaoxu Ma, Lei Dong, Lei Tian, Mei Zhou
Modern neuroscience research believes that synaptic plasticity is closely related to the learning and memory of higher animals. According to Hebb’s theory, synaptic plasticity is the basis of the mechanisms regulating learning and memory at the cellular level (Hebb 1949). Long-term potentiation (LTP) is one of the important manifestations of synaptic plasticity, and it is involved in the formation of brain learning and memory (Teyler and DiScenna 1987; Bliss and Collingridge 1993; Cooke and Bliss 2006), while stable long-term potentiation or long-term depression (LTD) can be induced on the Schaffer collateral branches in the hippocampal slices, representing the best model for studying the efficiency of synaptic transmission (Malenka and Bear 2004). Rahman et al. (2013) believed that the study of isolated brain slices may represent a bottom-up research method, and it has the advantage to precisely control the external stimulation, regulate neuron morphology and synaptic activity, and clarify the acute effects on pyramidal neuron cell bodies and axon ends. Therefore, isolated hippocampal slices have become a powerful tool to explore the effects of magnetic fields on the brain. However, LTP induction is clearly reduced with advancing age. Indeed, long-term potentiation was inducted by a stronger stimulation in the hippocampal CA1 region of aged rats (Pereda et al. 2019). The brain slices of SD rats at the age of 3 weeks show more evident CA1 region, they are more sensitive to external stimuli, and they show a better LTP induction effect.