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Stem Cell Transplantation After Middle Cerebral Artery Occlusion

Stem cell lines have been and are being developed to treat damage in the central nervous system after stroke. Stem cells are able to migrate to areas of damage and to differentiate into neurons and glia. Grafts of murine stem cells have been shown to promote recovery from behavioral dysfunction after s ...

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Production of Transgenic and Mutant Mouse Models

Manipulation of the rodent genome by deliberately inserting (transgenic) or removing (knockout) a gene of interest or indeed by selectively breeding animals with a spontaneous or random mutation producing a trait of interest has been developed over several years. Mouse “fanciers” have ...

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Endogenous Brain Protection: Models, Gene Expression, and Mechanisms

Almost all injurious stimuli, when applied below the threshold of producing injury, activate endogenous protective mechanisms that significantly decrease the degree of injury after subsequent injurious stimuli. For example, a short duration of ischemia (i.e., ischemic precon ...

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3-Nitropropionic Acid Model of Metabolic Stress: Assessment by Magnetic Resonance Imaging

3-Nitropropionic acid (3-NPA) is a potent mitochondrial inhibitor that can be administered systemically to create a progressive and localized striatal neurodegeneration mimicking many of the pathological features of Huntington’s disease and other forms of metabolic compro ...

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Practicalities of Genetic Studies in Human Stroke

Considerable evidence suggests genetic factors are important in the pathogenesis of multifactorial stroke. However, studies identifying the underlying genes have been largely disappointing. This chapter reviews the different approaches and their relative merits. It is lik ...

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Evaluation of the Interactions of Common Genetic Mutations in Stroke

Stroke is a common entity. It is the third leading cause of death and the leading cause of adult disability in the developed world. More than 110 heritable disorders, more than 175 genetic loci, and more than 2050 unique mutations predisposing to stroke are known. Although ischemic stroke can result f ...

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Technologies of Disease-Related Gene Discovery Using Preclinical Models of Stroke

Stroke is a clinically defined neurological syndrome characterized by rapidly progressing symptoms and signs of focal loss of cerebral function. The initiation, propagation, and maturation of ischemic stroke are associated with de novo expression of multiple genes in endogenous ...

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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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