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V S Caviness

Publications and source records attributed to V S Caviness.

At least 19 recordsLinked to original sources
PubMed1992

Dynamic changes in the density of radial glial fibers of the developing murine cerebral wall: a quantitative immunohistological analysis.

The density of radial glial fibers in the developing murine cerebral wall decreases dramatically during the terminal week of gestation. The present analysis characterizes these variations of fiber density quantitatively. Radial glial fibers were stained with monoclonal antibody RC2. Fibers were counted in a standard area of 2,000 microns2, passing orthogonally to the fiber long axis. At E14, fiber density is maximum and relatively uniform throughout the full width of the cerebral wall. Subsequently, the overall glial fiber density decreases and fiber density gradients emerge in the transmural span of fibers. These radial fiber density gradients are marked by sharp declines at the level of the ventricular-subventricular zone and in the zone of transition between intermediate zone (IZ) and cortical plate. In the interval E14-P0, the decrease in densities of fibers crossing the IZ is commensurate with the predicted diluting effects of tissue expansion with growth. By contrast, the decrease in fiber densities in ascent across the cortical plate beyond E14 through E17 exceeds that predicted by growth. The observations suggest that a substantial population of radial glial fibers do not span the full ventricular zone to the cerebral surface. A major contingent appears to extend only as far as the external sagittal stratum/subplate through E16. Subsequently, at a time when supragranular cortical layers are being assembled, the full set of fibers appears to extend more uniformly through the cortical strata. The late surge of fibers would be appropriate to the intercalation of groupings of neurons of the supragranular layers.

Animals↗
PubMed1992

BUdR as an S-phase marker for quantitative studies of cytokinetic behaviour in the murine cerebral ventricular zone.

BUdR incorporation into replicating DNA, detected immunohistochemically, is used as an S-phase marker in the proliferative cell populations of the cerebral wall of the mouse embryo on the 14th gestational day (E14). The analysis initiates a series of studies concerned with the cytokinetic behaviour and cell output of proliferative populations involved in neocortical histogenesis. On E14 there are two periventricular proliferative zones in the cerebral wall. These are the ventricular and subventricular zones. The ventricular zone is a pseudostratified epithelium. DNA replication occurs with the cell nucleus in the outer zone of the epithelium and mitoses at the ventricular surface. Prior applications of BUdR for studies of cytogenesis in the CNS have been extended in two principal ways: (1) basic fuchsin was used as counterstain for BUdR-negative nuclei and (2) labelling indices were determined separately in strata or bins, 10 microns in height, through the full depth of the ventricular zone and overlying cerebral wall. It was established that a single injection of 50 micrograms g-1 into the pregnant dam was associated with labelling of 100% of nuclei in S-phase over an interval extending from 15 min to at least 2.0 h after injection. The zone where nuclei are undergoing S-phase (S-phase zone) extends through the outer four bins of the ventricular zone. The method has high quantitative reproducibility with an SE for labelling indices in bins within the S-phase zone less than 10% of the average values. Evidence is provided that BUdR incorporation is initiated with the nucleus in the outer aspect of the S-phase zone. The efficiency of incorporation of the marker is reduced as nuclei near the end of DNA replication and move to the inner aspect of the S-phase zone.

Animals↗
PubMed1992

Quantitative magnetic resonance imaging and studies of degenerative diseases of the developing human brain.

The Rett syndrome is a progressive disorder which is associated with regression of psychomotor development and precipitous deceleration of brain growth during the first year of life. General histopathological surveys in postmortem specimens have identified degeneration of subpopulations of neurons of the nigrostriatal system but no other evidence of degenerative process. Magnetic resonance imaging-based morphometry may usefully guide application of rigorous but demanding quantitative histologic search for evidence of neuronal degeneration. The volumes of the principal set of cortical and nuclear structures of principal interest in the disorder may be measured by currently available MRI-based methods. Optimized levels of precision now allow detection of volumetric changes over time in the same brain of approximately 10% at the 95% confidence level.

Brain↗
PubMed1991

Ontogeny of radial and other astroglial cells in murine cerebral cortex.

Three cell forms of astroglial lineage populate the prenatal and early postnatal murine cerebral wall. In the present review we consider the ontogeny of these cell forms with respect to histogenetic events of the perinatal period. Classic bipolar radial glial cells predominate prior to E17. The bipolar coexist with monopolar radial forms in the perinatal period. Both bipolar and monopolar radial forms coexist with multipolar astrocytes in the course of the first postnatal week and are ultimately succeeded by the multipolar cells. The shift from bipolar to monopolar radial forms is initially coincident with translocation of somata of bipolar cells from the ventricular zone to the upper intermediate zone and cortical strata. Arborization appears to occur both at the growing tips and along the shaft of the processes of both bipolar and monopolar radial cell types. As arborization continues, the processes of the monopolar radial cells come to resemble those of the multipolar astrocytes. Eventually the radial cells are fully transformed into the multipolar astrocytic forms. During this period of transition, radial processes in the cortex appear to be degenerating, suggesting that regressive processes contribute to the cytologic transformation. This sequence of transformations begins late in the period of neuronal migration and continues through the early stages of growth and differentiation in the murine cerebral cortex. The signals that induce these changes may arise from differentiating neurons within the cortex. These transformations occur at a time when radial glial fibers are no longer required as guides for neuronal migration, and the glial population assumes new roles related to the development and operation of cortical neuronal circuits.

Animals↗
PubMed1990

Glial process elongation and branching in the developing murine neocortex: a qualitative and quantitative immunohistochemical analysis.

Cells of astroglial lineage in the murine cerebrum undergo a succession of transformations during prenatal and early postnatal development. The bipolar radial cell, the earliest astroglial form to appear, provides a radially aligned, parallel array of fibers that serves as a guide to neuronal migration. The multipolar astrocyte is the representative of this lineage that persists in the adult cerebrum. The processes of the multipolar astrocytes form a complex reticulum, which is considered critical to the development, function, and maintenance of neural circuits. A monopolar radial cell appears to be transitional between the two. The shift from the radial glial fiber system to a diffuse glial network is achieved largely in the E17-P2 interval in the mouse. This phenomenon has been studied qualitatively and quantitatively by staining cerebral tissue with monoclonal antibody RC2, a specific and sensitive ligand for cells of astroglial lineage in the mouse. Elongation and branching of glial processes contribute to the glial transformation. Elongation of radial fibers occurs under the guidance of other radial glial fibers (fasciculated elongation) or independently of other fibers (nonfasciculated elongation). Fasciculated elongation results in an increase in the density of radial glial fibers that span the cortical layers. Nonfasciculated elongation appears to be associated with process branching. This is the initial event in transformation of the bipolar radial cells to monopolar radial or multipolar cells. Only nonfasciculated elongation is characteristic of processes of the monopolar radial cells and multipolar astrocytes. Branching of the processes of all three cell forms appears to occur both by bifurcation at the elongating tip and by sprouting from the fiber shaft. Elongating fibers are tipped by growth cones that are relatively simple in shape as compared to those observed at the tips of elongating axons. Growth cones at the tips of nonfasciculated fibers are more complex in form than those at the tips of radial fibers elongating in contact with other radial fibers.

Animals↗
PubMed1990

Neuron migration within the radial glial fiber system of the developing murine cerebrum: an electron microscopic autoradiographic analysis.

The present analysis provides direct evidence in the mouse that in the course of course of neocortical histogenesis, contact between migrating neurons and the surfaces of radial glial fibers is both invariant and relatively selective. The analysis characterizes in detail the migratory behavior of the individual migrating cell with respect to the overall radial glial fiber system as this system varies systematically in its structure with ascent through the strata of the cerebral wall. A quantitative study of the relationships between the radial glial fibers confidently identified by their glycogen content and the migrating neurons marked autoradiographically by injection of [3H]thymidine was also performed at the ultrastructural level on tangential sections at different pallial levels in E16 and E17 embryos. The overall set of observations lend support to the hypothesis that radial glial fibers act specifically as guides to neuronal migration and illustrate the nature of the cell-to-cell interaction which serves this cellular process critical to neocortical histogenesis.

Animals↗
PubMed1990

Organization of radial glia and related cells in the developing murine CNS. An analysis based upon a new monoclonal antibody marker.

A monoclonal antibody, RC1, has been generated which provides a selective and sensitive immunohistochemical marker of radial glial cells and related cell forms during development of the mouse CNS. Beginning on embryonic day E10, immunocytochemistry performed on cryostat sections stains throughout the CNS a subpopulation of cells in the ventricular zone with radial processes that terminate with endfeet at the pial surface. These processes become fasciculated and attain maximal densities by E12-14 in the spinal cord and lower brainstem and by E14-16 in the midbrain, cerebellum and forebrain. Fasciculation is especially prominent for a subclass of these cells at the midline of the brainstem and spinal cord. As nuclear and cortical structures develop, the trajectories of the radial fiber fascicles undergo systematic and region-specific distortions in their initially simple linear configuration, in the process maintaining a consistent spatial registration of germinal ventricular zones with distal sites of assembly of post-migratory neurons. In the late fetal period, radial glial progressively disappear and scattered immature astrocytes bearing multiple fine processes appear in most regions of the CNS. In the spinal cord, a transitional unipolar radial form is identified in the emerging ventral and lateral funiculi between E13 and E17. In the cerebellum, precursors to the unipolar Bergmann glial cell are identified by E15, and in the retina, precursors of the bipolar Müller cell are identified by E16. Postnatally, RC1-stained radial glia become sparse, and after one week, immunoreactive cells include only ependymal cells, hypothalamic tanycytes, Bergmann glia, Müller cells, a unipolar radial form in the dentate gyrus, and a subpopulation of white matter astrocytes. These results suggest that radial cells of astroglial lineage comprise a diverse set of cell classes which subserve multiple functions in the developing and adult brain.

Animals↗
PubMed1989

Dynamic structure of the radial glial fiber system of the developing murine cerebral wall. An immunocytochemical analysis.

Dramatic changes occur in the radial glial fiber system of the murine forebrain in the course of neocortical histogenesis. Initially, prior to substratification of cortical and subcortical anlagen between E13 and E14, the system is uniformly radial in alignment. It appears to achieve maximum density and to be highly uniform in structure throughout its radial span, both in terms of apparent fiber density and the pattern of arrangement of fibers in fascicles. Subsequent to E14, concurrently with rapid growth of the cerebral wall and with the differentiation of the cortical substrata and intermediate zone, the subcortical segment of the system becomes laterally arced while the transcortical span of the system remains radially aligned. Although the spacing between fascicles changes little, there is an apparent general drop in fiber density associated with a progressive reduction in the number of fibers per fascicle. The changes in relative positioning of the fibers and the apparent decline in fiber density are most dramatic within the developing cortical plate and subplate and may be of specific significance for the migration and radial assembly of the neurons in the supragranular neocortical layers.

Animals↗
PubMed1989

Magnetic resonance imaging-based brain morphometry: development and application to normal subjects.

A semiautomated computerized method of in vivo morphometric analysis that is based upon high-resolution three-dimensional magnetic resonance imaging has been developed. This morphometric method is efficient and is of greater analytical precision than any other morphometric method currently applied to living human tissue. Including error inherent in image data acquisition, the aggregate error of the methodology, as estimated by the phantom studies, ranges from 4.5 to 9.6%, with incremental error above 4.5% a function of magnetic resonance slice thickness. This method was applied to magnetic resonance scans of 7 normal volunteers. The derived volumes of whole brain and of individual substructures were closely concordant with previously published volumes of normal fresh (unfixed) brains obtained post mortem. This morphometric methodology is potentially applicable to any structure or lesion that can be visualized by magnetic resonance imaging.

Adolescent↗
PubMed1989

Magnetic resonance technology in human brain science: blueprint for a program based upon morphometry.

Magnetic resonance images provide a comprehensiveness of analysis of the human brain and levels of resolution never achieved by other modes of pathoanatomic analysis. We review a strategy and technology of MRI-based image analysis which extracts independent measures of brain volumes, shape and position. These parameters are readily correlated with behavioral as well as physiological measures derived from PET and the emerging technology of MRI-based in vivo spectroscopy. A coordinate program which draws upon these methods will have wide applications in human brain science and the study of dynamic properties of human brain disease.

Brain↗
PubMed1989

Structural and chemical alterations in the cerebral maldevelopment of fetal cerebro-hepato-renal (Zellweger) syndrome.

The cerebra of four abortuses (estimated gestational age 14-22 weeks), diagnosed as cerebro-hepato-renal (Zellweger) syndrome in utero, were examined morphologically with light microscopic, immunocytochemical and ultrastructural techniques and biochemically with gas liquid chromatographic assays for cholesterol ester fatty acids and plasmalogens. Centrosylvian architectonic abnormalities consisting, in part, of thin cortical plates and broad subcortical heterotopic zones were found in all abortuses. Astrocytes, neuroblasts, immature neurons and radial glia contained abnormal pleomorphic cytosomes, presumably of variable lipid composition. The same areas exhibited increases in cholesterol ester very long chain fatty acids and decreased plasmalogens. A pathogenetic hypothesis, proposing that regional tissue constraints act in concert with a peroxisomal-derived biochemical abnormality to impede centrosylvian neuronal migration, is discussed.

Adrenoleukodystrophy↗
PubMed1989

Subtorcular occipital encephaloceles. Anatomical considerations relevant to operative management.

Three cases of occipital encephalocele, one with associated myelomeningocele, are presented. All received preoperative evaluation with magnetic resonance imaging. Such studies provide optimal demonstration of the cerebral and hindbrain anatomy to guide operative treatment and formulate prognosis. Review of available radiographic, operative, and pathological information suggests that most, if not all, occipital encephaloceles are associated with an anomaly of the hindbrain, and the usual anomaly is a rhombic roof encephalocele. In such cases, the site of cranial herniation is caudal to the torcula, regardless of the presence or absence of occipital lobe tissue within the sac. Experimental and clinical analysis suggests that occipital encephaloceles most likely arise from abnormalities in the development of the skull base.

Brain Stem↗
PubMed1988

Identification of radial glial cells within the developing murine central nervous system: studies based upon a new immunohistochemical marker.

The monoclonal antibody RC2 was generated in mouse by conventional hybridoma methodology. The antigen recognized by RC2 is robust, allowing aldehyde fixation appropriate to high resolution light and electron microscopic analyses. From the neural tube stage of fetal development the antibody delineates throughout the central nervous system a subpopulation of neuroepithelial cells which have a radial bipolar morphology. A descending process extends to the ventricular margin, and an ascending process contacts the glial limiting membrane by one or more endfeet varicosities. The persistence of these cells through the neurogenetic period allows their identification as radial glial. From as early as E9-10 the fibers appear to be organized in simple straight fascicles. Later in fetal development these fascicles show marked region-specific transformations in density and trajectory, particularly in association with cerebral corticogenesis and with cerebellar and basal ganglia development. The bipolar forms continue to stain with RC2 until they disappear in the postnatal period. Concurrently with a progressive perinatal loss of stained bipolar radial glia, RC2 identifies multipolar cell forms at various levels of the brain wall, as consistent with the transformation of radial glia into astrocytes. RC2 also recognizes monopolar cell forms in the spinal cord and the cerebellum as early as E15, and in the dentate gyrus of the hippocampal formation from the day of birth. Monopolar forms in the cerebellum are inferred to be progenitors of Bergmann glia. Although Bergmann glia are known to persist in adult life, these cells do not stain with RC2 beyond the 2nd postnatal week. The robustness of the antigen recognized by RC2 makes this probe a valuable tool to study the morphological transformations of the bipolar radial glia during their mitotic turnover. It also provides a sensitive stain for the study of the organization and the histogenetic role of the overall radial fiber system.

Aging↗
PubMed1988

Mitotic cycling of radial glial cells of the fetal murine cerebral wall: a combined autoradiographic and immunohistochemical study.

Radial glial cells of the embryonic murine cerebral wall are selectively labeled by staining with antibody RC1. In order to study the mitotic cycling of these cells, we combined RC1 immunohistochemistry and autoradiographic analysis following [3H]thymidine injection at 1, 2, 6, 48 h prior to sacrifice. Many radial glial cells, i.e. RC1-positive cells, incorporate the DNA tracer and hence must be mitotically active. Other proliferative cells of the ventricular zone do not stain with RC1. With the transition from S to M phase, the nuclei of the radial glial cells participate in the interkinetic 'to-and-fro' nuclear translocation characteristic of the non-radial glial cells of the ventricular zone. The density of radioactive grains over nuclei of both RC1-positive and negative cells of the ventricular zone becomes similarly reduced in the 48 h following the [3H]thymidine incorporation. Thus, the subpopulation of radial glia with nuclei within the ventricular zone which have incorporated the DNA tracer does not appear to become arrested in a prolonged G1 phase. The results suggest that the ventricular zone includes at least two subpopulations of stem cells, neuronal and radial glial. Radial glial cells, i.e. RC1-positive cells, are inferred to serve initially as a progenitor population for new radial glial cells. Later in development, they probably become a source of other cells of astroglial lineage.

Animals↗
PubMed1988

Cellular migration in developing cerebral wall explants in vitro.

Explants of the developing cerebral wall of the embryonic mouse survive in rotation-mediated culture for at least 3 days. [3H]Thymidine-labeled cells are initially located in the ventricular zone but after two days in vitro are located in a middle cell-rich layer. Cortical explants can thus be used as a model system in which the molecular mechanisms of neuronal migration in the developing cerebral wall can be examined.

Animals↗