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R C Switzer

Publications and source records attributed to R C Switzer.

33 records · Page 2Linked to original sources
PubMed1984

Brain traits through phylogeny: evolution of neural characters.

We have previously derived a hypothetical tree of the lines of mammalian descent, based upon a comprehensive numerical taxonomic cross-analysis of primitive and derived states of 15 brain traits in 38 representative species. In this communication we use this tree to describe the probable sequence of changes that have taken place in phylogenetic history. 2 characters proved to be multiply convergent, occurring in parallel in several disparate lines of descent. The remaining 9 characters each appeared in ancestors of one or another of the lineages and characterize related progeny.

Animals↗
PubMed1983

Auditory and vestibular pathology of seizure-prone chicks.

The mutant sex-linked lethal recessive px (paroxysmal) gene, expressed in White Leghorn chicks (Gallus domesticus) causes seizures beginning on approximately day 8 post-hatching. Seizures are spontaneous and inducible by auditory but not by photic stimulation. Prior to seizure onset px chicks are indistinguishable from non-px siblings. With seizure onset is a decrease in food intake which causes deterioration and death by 4-10 weeks of age. In a preliminary histological study conducted on 22-day-old seizure-prone chicks, brains were perfused and sections treated according to a modified cupric-silver staining technique. Nuclei and fiber tracts of px auditory and vestibular systems were extensively degenerated; control brains showed essentially no degeneration. A second experiment was conducted with preseizure chicks to determine whether and to what extent degeneration occurs prior to seizure onset. Deep nuclei of px cerebellum appeared to be the first seriously affected (5 days of age). Extent of degeneration progressed steadily over time through 20 days of age, by which time all components of the two sensory systems were maximally affected. Ambient noise did not affect onset or extent of degeneration, nor did it affect onset of seizures.

Acoustic Stimulation↗
PubMed1983

Phylogeny through brain traits: the mammalian family tree.

Wagner trees based on the analysis of 15 brain characters scored on 154 specimens of 134 mammalian species show consistent patterns of relationship among the taxa, i.e. (1) monotremes are the primitive complement of the group uniting marsupials and placentals; (2) among marsupials, diprotodont Australian forms are more derived; (3) placental mammals divide into two groups of orders, roughly the ferungulates (carnivores, ungulates, and subungulates) and the unguiculates-plus-gliroids (chiropterans, dermopterans, lagomorphs, rodents, primates, and insectivores including elephant shrews); (4) edentates sit at the base of or just before the placental dichotomy; (5) the tree shrew and tarsier show the same pattern of distribution of brain traits as some rodents, as do prosimians and New World monkeys.

Animals↗
PubMed1982

The globus pallidus and its rostroventral extension into the olfactory tubercle of the rat: a cyto- and chemoarchitectural study.

The globus pallidus is characterized by a high iron content and the distribution of the ferric iron in the rat brain provides evidence that globus pallidus extends rostroventrally below the anterior commissure and into the olfactory tubercle. The extension of the globus pallidus into the olfactory tubercle is consistent with the notion of the ventral striatum,14 in the sense that it provides for an expected close proximity between the striatum and the globus pallidus throughout the dorsoventral extent of the corpus striatum. The distribution of enkephalin, and of acetylcholinesterase- and succinate dehydrogenase-positive neurons is also consistent with an extension of the ventral part of globus pallidus to the base of the forebrain in the rat. Since part of the ventral pallidum corresponds to a region that is usually referred to as the subcommissural part of the substantia innominata, it seems reasonable to restrict the term substantia innominata to the more caudally-located sublenticular part of the substantia innominata.

Acetylcholinesterase↗
PubMed1982

Phylogeny through brain traits: fifteen characters which adumbrate mammalian genealogy.

Fifteen characters of brain organization are identified for which primitive and derived states can be distinguished, and which are thus useful in reconstructing mammalian phylogeny. The states of the characters are numerically coded in sequence from most primitive to most derived, to facilitate reciprocal comparisons in comprehensive genealogical analyses. The characters include certain features of cerebral circulation, cytoarchitecture, fiber pathways, and sensory projections. Seven characters are shared with nonmammals, a fact which makes then particularly useful for establishing their primitive vs. derived states; the other eight characters are features peculiar to mammals. Ten characters provide impressive reinforcement for traditional major grouping of the species, while five provide bases for new ideas about mammalian relationships.

Animals↗
PubMed1982

Phylogeny through brain traits: the distribution of categorizing characters in contemporary mammals.

The varying states of 15 characters of the central neural organization are tabulated as they occur in each of 147 mammalian species. For each character and species, scores are entered designating the primitive or derived state of the character as it is observed in that species. This tabulation provides data in numerically ordered form for multiple analyses of possible phylogenetic relationships which take into account variations in several different characters simultaneously.

Animals↗
PubMed1980

Phylogeny through brain traits. Relation of lateral olfactory tract fibers to the accessory olfactory formation as a palimpsest of mammalian descent.

In mammals the fibers of the dorsal lateral olfactory tract either pass under the accessory olfactory formation, or they penetrate through it separating the internal granule cells from the output cells. The use of this trait as a phylogenetic indicator in 181 specimens representing 131 species of 16 orders yielded evidence for common ancestry of Insectivora, Chiroptera, Dermoptera, Rodentia, and Primates (including Tupaia), since all share the derived trait, their dorsal lateral olfactory tract fibers passing through the accessory olfactory formation. Carnivora (including Pinnipedia), Hyracoidea, Perissodactyla, and most Artiodactyla share the primitive condition (fibers passing under) with the one order of monotremes and three marsupial orders. The Edentata and Lagomorpha may be separate from the two major placental groups and from each other, or they may represent successive stages in the evolution of the derived state through progressive alterations in the relative chronology of development of olfactory system components, or one or both orders may occupy an ancestral position with respect to the dichotomy within placental mammals.

Animals↗
PubMed1979

Trace polypeptides in cellular extracts and human body fluids detected by two-dimensional electrophoresis and a highly sensitive silver stain.

Development of a highly sensitive silver stain permits the characterization of trace cellular and body fluid proteins separated by the two-dimensional electrophoresis technique of O'Farrell. Many of the proteins detected by the silver stain in urine, spinal fluid, amniotic fluid, and cells were undetected with the widely used Coomassie blue stain. Trace polypeptides observed in Escherichia coli cell lysates with this silver stain could be detected previously only by growth in radioactive precursors followed by lengthy autoradiography. In situations that do not permit the use of radioactive labeling, as in human clinical studies, the enhanced ability to detect proteins achieved by the silver stain will facilitate metabolic studies and the screening for protein abnormalities in mutational studies and in genetic diseases.

Amniotic Fluid↗
PubMed1977

Absence of mitral cells in monolayer in monotremes. Variations in vertebrate olfactory bulbs.

An invariant feature of the olfactory bulb in placental and marsupial mammals is the arrangement of the perikarya of mitral cells in a monolayer. Contrasting with this is the arrangement found in the olfactory bulbs of the monotremes, platypus and echidna, where the large perikarya are not only absent from the position of a monolayer (usually forming the external boundary of the internal plexiform layer) but occupy a region which would characterize them as tufted cells. In other classes of amniote vertebrates, reptiles and birds, the placement of large perikarya in the olfactory bulb ranges from a compact layer to a broad band. Such an overview among several vertebrate classes suggests that a monolayer of mitral cells may be a specialized subset of the tufted-mitral cell population. The accessory olfactory formation among mammals also exhibits variation in the compactness of the large perikarya: a broadband in most but a compact layer in a few others such as the chinchilla and the capybara. Such specialized alignment of perikarya (and, consequently, of their dendritic and axonal elements) may enable more refined signal processing than does random alignment of these elements. Such speculations can be tested using appropriate phylogenetic sampling, and monotremes provide particularly advantageous test cases.

Anatomy, Comparative↗
PubMedDate not supplied

Application of silver degeneration stains for neurotoxicity testing.

Silver staining procedures have been used in numerous ways to render a variety of physical and biological features visible. In biological tissue, histologic protocols use silver to visualize diverse structures or features, such as reticulin, melanin, fungi, chromosome bands, nucleolar organizing regions, and different features in the nervous system. A comparison of the specific steps in these protocols indicates that the silver is "directed" to stain any given feature by the type of fixation, the pretreatment ("mordanting"), the composition of the silver-containing solution(s), and the form of development (reduction). Since the mechanisms of staining have not been understood historically (nor are they now), each method was developed by trial and error. Keystone methods such as those of Bodian and Bielschowsky exploit the nervous system's affinity for silver (argyrophilia). The beginning of a new era in brain research came with the recognition that distinct silver-impregnated morphologic changes occurring in damaged axons could be used for tracing axon pathways in experimental animals with specifically placed lesions. Improvements in staining methods used to selectively impregnate the disintegrating axons but to leave normal axons unstained were achieved by Nauta and Gygax (early workers with these procedures) and spawned a host of method variations known as the "Nauta" methods. Of these, the Fink-Heimer and de Olmos cupric-silver methods were able to unambiguously demonstrate disintegrating synaptic terminals, thereby allowing complete tracing of axon pathways. The late 1970s and 1980s witnessed innovative applications of these techniques. The silver methods once used to trace axon pathways became indicators of the extreme endpoint of neurotoxicity: disintegrative degeneration of neurons induced by neurotoxic chemicals that were administered systemically. The hallmark of neurotoxic substances is the selectivity with which each destroys specific populations or subpopulations of neurons. The high contrast and sensitivity of the silver degeneration stains greatly facilitate the screening process to detect these affected populations, especially when there is no basis for knowing where in the brain to look for damage. More recently, in addition to expanded use in screening for neurotoxic effects, the silver degeneration stains are being used to chart the neuron populations undergoing programmed cell death in the developing brain. Other newly developed silver methods have been refined to show nondisintegrative degeneration, such as the plaques,and tangles of Alzheimer's disease.

Animals↗
PubMedDate not supplied

MK-801 neurotoxicity in cupric silver-stained sections: lesion reconstruction by 3-dimensional computer image analysis.

Routine histopathologic evaluation of the brain (paraffin embedding, hematoxylin and eosin staining) makes it difficult for an investigator to identify the overall location and relative extent of lesions as they relate to neural substructures. Moreover, it is very difficult to convey this information to others who are less familiar with neuroanatomy. This study combined a 3-dimensional imaging program with a cupric silver stain for neuronal degeneration in order to determine the location and extent of a focal lesion produced by MK-801 (dizocilpine maleate), a glutamate receptor antagonist that induces necrosis in a small population of neurons in the cortex of rats. A male Sprague-Dawley rat was treated with a subcutaneous dose of MK-801 (10 mg/kg) and was perfused with fixative through the left ventricle 3 days after treatment, a time point known to reveal maximal neurotoxic effects. The brain was embedded in a gelatin matrix, frozen, and serially sectioned at a thickness of 40 microm. The cupric silver method of de Olmos was used to stain frozen sections at 320-microm intervals. Using a color charged-couple device (CCD) camera and a macro lens, a series of 2-dimensional images, which encompassed the entire rostral to caudal extent of the brain, was captured. A computer program was written to define internal and external boundaries in these 2-dimensional images. Then, 3-dimensional reconstructions were generated on a Silicon Graphics workstation using IRIS "Explorer." The quality of the 3-dimensional reconstructions allowed for easy identification of various neural substructures while clearly revealing the exact location and extent of the resulting necrotic neurons that were positively identified by the cupric silver stain. This 3-dimensional lesion reconstruction method provides a powerful tool for conveying spatial information about the nature of neurotoxic lesions in the brain. In addition, it may be used to investigate further dose-response relationships and the effects of other neurotoxicants.

Animals↗
PubMedDate not supplied

Integrated evaluation of central nervous system lesions: stains for neurons, astrocytes, and microglia reveal the spatial and temporal features of MK-801-induced neuronal necrosis in the rat cerebral cortex.

Routinely processed, hematoxylin and eosin (H&E)-stained slides are typically used to assess the morphologic integrity of the central nervous system in neurotoxicity safety studies. However, the value of special stains for improving neuropathologic evaluations during the assessment of neurotoxicity has been emphasized in the neuroscience literature and by regulatory agencies. The primary objective of the present study was to characterize the spatial and temporal changes in neurons, astrocytes, and microglia after dizocilpine maleate (MK-801)-induced focal neuronal necrosis in the posterior cingulate/retrosplenial (PC/RS) cortex of the rat. A secondary objective was to evaluate the application of special stains and a novel sectioning procedure for detecting neurotoxicity. Sixty adult male Sprague-Dawley rats were treated with sterile water vehicle or 10 mg/kg MK-801 and perfused through the left ventricle (pumped at 65 mm Hg pressure) with 10% neutral buffered formalin or 4% paraformaldehyde at 4 hr and on days 1, 3, 7, 14, and 28 after treatment. For light microscopic evaluation, brain sections were stained with H&E, a special cupric-silver (CS) stain that selectively impregnates degenerating neurons and makes them readily evident, glial fibrillary acidic protein (GFAP) immunohistochemistry for astrocytes, and Griffonia simplicifolia isolectin B4(GSA) histochemistry for microglia. Brains perfusion-fixed with 4% paraformaldehyde were prepared for CS staining with a novel frozen-sectioning procedure for multiple embedding in a composite gelatin block. In H&E sections from treated rats, necrotic nerve cell bodies were observed in PC/RS cortical layers 3 and 4 on days 1, 3, 7, and 14, but not on day 28. These necrotic neurons required high magnification for detection (x20 objective, x10 ocular). In contrast, degenerating neurons selectively stained with CS were observed in the same location as necrotic neurons seen with H&E but at low magnification (x2 objective, x10 ocular). Cupric-silver staining showed details not seen with H&E, including dendritic and axonal degeneration with progressive fragmentation. Beginning on day 3, GFAP immunohistochemistry revealed hypertrophic astrocytes in a diffuse pattern throughout the region of cell body necrosis, a change that persisted throughout the study. However, GSA lectin histochemistry identified a few reactive microglia on day 1 in a multifocal pattern throughout the region of cell body necrosis. Reactive microglia were observed on days 3, 7, and 14, but not on day 28. Glial changes observed with H&E staining were limited to an increase in the cellularity of glial cell nuclei in the area of neuronal necrosis. This study provides a comprehensive and integrated view of the temporal changes occurring in neurons, astrocytes, and microglia during acute neurotoxic injury. Moreover, advantages for using new staining and sectioning methodologies to enhance the toxicologic evaluation of the central nervous system are demonstrated.

Animals↗