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神经生物学

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Quantitative Analysis of Gene Transcription in Stroke Models Using Real-Time RT-PCR

Many researchers have sought to study changes in gene expression in preclinical models of stroke. These range from in vitro models of ischemia, neuronal death, and regeneration to in vivo animal models aimed at replicating pathologies and regenerative processes typical of the clinical s ...

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Effective Analysis of Genomic Data

High-throughput biotechnology has enabled genome-wide investigation of gene expression and has the potential to identify genes that have a role to play in focal cerebral ischemia, as well as many other interventions. The advent of this technology has also led to the generation of large amoun ...

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Pragmatic Target Discovery From Novel Gene to Functionally Defined Drug Target: The Interleukin-1 Story

The pro-inflammatory cytokine interleukin-1 (IL-1) has been proposed as a mediator of the acute neurodegenerative changes that occur following stroke. This is based largely on experimental studies in rodents, in particular the marked reduction in ischemic cell death seen when IL-1 rec ...

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Site-Directed Mutagenesis and Chimeric Receptors in the Study of Receptor-Ligand Binding

Prior to the cloning of G protein-coupled receptors (GPCRs), structure-function analysis of the ligand-binding properties of these receptors had for the most part been limited to study of the structure-activity relationships (SAR) of agonists and antagonists at the individual rece ...

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Approaches to the Stable Transfection of G Protein-Coupled Receptors

Heterologous expression in mammalian cell lines provides an invaluable tool with which to explore determinants of G protein-coupled receptor (GPCR) function. The use of stably transfected cell lines enables a receptor to be studied in the absence of other related receptor subtypes. With ...

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Acquisition of Drug Self-Administration

This review provides an overview of animal models of acquisition of drug reinforcement by discussing research findings from studies that used drugs such as cocaine, methamphetamine (METH), phencyclidine, and nicotine, as well as several routes of drug self-administration (SA). Theo ...

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Animal Models of Niacin-Nicotinamide Deficiency

The human disease caused by niacin (vitamin B3) deficiency is pellagra, a disease that at one time filled insane asylums all over the world before the function of niacin was discovered. The recognition of pellagra as an endemic disease in the US dates from Searcy’s report in 1907 (Strandell et al., 1989) d ...

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Animal Models of Hepatic Encephalopathies

Hepatic encephalopathy (HE) is a neuropsychiatric disorder that results from impaired liver function. In humans, hepatic encephalopathy occurs in two major forms: (1) Associated with acute or fulminant hepatic failure, a clinical syndrome resulting from severe inflammatory and ...

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Genetically Based Animal Models of Seizures

Seizure activity can be produced in experimental animals by a variety of methods. Other chapters in this volume detail these techniques, which include drug and chemical means, electroshock, and kindling models. Each of these methods of seizure induction has advantages and disadvantag ...

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The Kindling Model of Epilepsy

The term “kindling” is a particularly apt metaphor when used to describe the phenomenon discussed in this chapter. In a manner similar to that in which small burning twigs ultimately produce a large fire, repeated subconvulsive stimulation of the brain by electrical current or pharmacolog ...

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Chemically Induced Models of Seizures

The purpose of this review is to present an overview of various experimental models of chemically induced seizures. It is not intended to be an exhaustive review of all chemical models, but rather a “how to” description of some of the more popular models that have yielded important data concerning me ...

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Animal Models of the Wernicke-Korsakoff Syndrome

In humans, deficiency of thiamine (vitamin B,) is associated with two well-defined neurological disorders: a mixed sensorymotor neuropathy and the Wernicke-Korsakoff syndrome. Disturbances of thiamine metabolism may also play a role in other human diseases, such as infantile suba ...

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Quantitative Light Microscopic Autoradiography of 2-Adrenergic Radioligand Binding Sites

Adrenergic receptors (ARs) belong to the family of G-protein-coupled receptors and can be classified into three subfamilies, with each one having at least three distinct subtypes (1). Although all three subfamilies have similar affinity for the endogenous ligands norepinephrine and ...

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Distribution of 2A- and 2C-Adrenergic Receptor Immunoreactivity in the Central Nervous System

α2-Adrenergic receptors (α2-ARs) are G-protein-coupled receptors that mediate the inhibitory effects of norepinephrine and epinephrine in the peripheral and central nervous system (CNS). In the CNS, these receptors have been implicated in the regulation of analgesia, memory, and c ...

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Assay of Arachidonic Acid Release Coupled to 1- and 2-Adrenergic Receptors

AA is the precursor for prostaglandins, eicosanoids, and the endogenous cannabinoid ligands, such as anandamide (1). The major pathways that lead to the liberation of free AA from phospholipids are shown in Fig. 1. Phospholipase A2 (PLA2) provides a direct pathway for AA release and is the most comm ...

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Expression of -Adrenergic Receptors in Recombinant Baculovirus-Infected Insect Cells

Ever since the initial discovery of the structurally homologous G-protein-coupled receptors, the search has been ongoing for identifying suitable expression systems. Such systems should be easy to use, inexpensive, and appropriate for mass production. In addition, these systems s ...

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Redox Sensitivity of NMDA Receptors

The redox modulatory sites of the NMDA receptor consist of critical cysteine residues, which when chemically reduced, increase the magnitude of NMDA-evoked responses. In contrast, after oxidation, NMDA-evoked responses are decreased in size. In recent years, as endogenous sources of ...

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In Vitro Selection of Peptides Acting on NMDA Receptors

Phage-displayed random peptide libraries have been used to identify novel agonists and antagonists to a wide variety of receptors. Among these are a family of peptides that bind to the NMDA receptor subunit NR1 and non-competitively inhibit receptor channel activity (1). The peptide libr ...

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NMDA Receptor Pharmacology and Analysis of Patch-Clamp Recordings

There are two approaches to evaluation of the effects of drugs on steady-state ligand-gated receptor function: (1) concentration-response curves derived from whole-cell recordings and (2) analysis of single-channel recordings. Whole-cell currents are the average response of a la ...

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Determination of Membrane Topology of Glutamate Receptors

Glutamate receptors are large integral membrane proteins that belong to the class of ligand-gated ion channels. They constitute a family of receptors that are activated by binding of the neurotransmitter l-glutamate. Functional receptors are formed by assembly of several subunits a ...

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