The fine structure of human cerebral perivascular pericytes and juxtavascular phagocytes: their possible role in hydrocephalic edema resolution.

An electron microscopic study has been made of the perivascular cerebral pericytes and juxtavascular phagocytes in the human cerebral cortex. Biopsies from 16 hydrocephalic children and one 4-year-old normal child were analyzed. Pericytes showed vesicular transport demonstrating pericyte brain barrier alteration in hydrocephalus, which might help in the resolution of edema. Aggregation of vesicles, so obvious in the hydrocephalic material, was not seen in the control pericytes. Intercapillary channel (bridge) was seen in one instance. Phagocytic cells containing lipid vacuoles cellular debris and lysosomes were often observed in the vicinity of the microvasculature of the hydrocephalic biopsies. Occasional separation of a phagocytic pericyte from the vessel wall suggests that some juxtavascular phagocytes may be derived from pericytes.

Ultrastructural features of the human frontal cortex neurons of maturing and hydrocephalic cerebrum.

Human frontal cortex neurons of hydrocephalic infants were studied with electron microscope. A number of maturing neurones exhibited shrinkage and increased electron density of cytoplasmic matrix in the midst of gross hydrocephalic interstitial oedema. Remarkable preservation of growth cones and arrays of microtubules in a few neuronal perikarya and axons were discernible. Rows of normal looking neurones with parallel arrays of cisternae of rough endoplasmic reticulum were also detected. Thus, preservation of significant number of neurones was apparent even in cases of extreme hydrocephalus.

Ultrastructure of human cerebral macroglia and microglia: maturing and hydrocephalic frontal cortex.

Fifteen human cerebral cortical biopsies from children treated for hycrocephalus by shunt operation and one non-hydrocephalic "control" biopsy specimen were studied by electron microscopy. Marked differences between the ultrastructural features of oligodendrocytes and microgliacytes in the maturing and hydrocephalic material and the ultrastructure of control and adult specimens were seen. Proliferation of oligodendrocytes was commonly discernible. Microgliacytes exhibiting plesomorphic vacuoles and bundles of microfilaments were often observed.

Fine structural features of the cerebral microvasculature in hydrocephalic human infants: correlated clinical observations.

Four of 30 human cerebral cortex biopsies from infants ranging from four days to about ten years treated for hydrocephalus by shunt operations are described paying special attention to the vascular structures. The biopsy specimens were studied in semi-thin and ultrathin sections. Attention is drawn to the role of pinocytotic vesicles found in capillaries and smaller vessels as a possible transcellular route for the hydrocephalic oedema resolution. No intercellular dehiscences or the so called blisters were observed. With the passage of time, the number of membrane bound vesicles increased and arrays of pinocytotic vesicles were discernible both on the abluminal as well as luminal aspect of the capillary wall. Additionally, larger vacuoles containing electron-dense material, apparently undergoing autolysis, were also detected. The basal lamina was of uneven thickness and at places duplicated. Hypertrophic pericytes exhibited remarkable oedamatous changes, increased vesicular or vascular transport, demonstrating pericyte brain-barrier dysfunction. Swelling of the astrocytic end-feet bordering the capillaries was remarkable. These findings indicate that the CSF or oedema fluid is absorbed into the vascular system via a transendothelial pathway.

Clinical and ultrastructural observations of maturing human frontal cortex. Part I (Biopsy material of hydrocephalic infants).

Three of 30 human cerebral cortex biopsies from infants treated for hydrocephalus by shunt operation are described. The descriptions include an account of their case history, the clinical methods, and the operational procedures. The biopsy specimens were studied in semithin and ultrathin sections. Attention is drawn to normal synapse formation but also to neuronal degenerative changes due to hydrocephalus.

Somatotopic analysis of fibre and terminal distribution in the primate corticospinal pathway.

This is an anatomical study of the precision of fibre and terminal orderliness in the direct corticospinal projection. It was conducted to assess the degree of somatotopy in this projection in primates and to deduce the mechanism(s) possibly responsible for guiding fibres to their segmental destinations in development. As fibres leave the cortex they are grouped in an orderly way so as to be placed (within the pathway cross-section) according to their points of origin. Systematic neighbourhood relations are rather abruptly broken down as the descending pathway traverses the pons. Fibres are randomly distributed within each medullary pyramid and this disorderliness is maintained throughout the spinal pathway in the dorsolateral columns. Nonetheless, fibres exciting thumb movements end selectively at cervical levels. Fibres exciting foot movements end preferentially at lumbar levels but also show a secondary maximum of terminations in cervical segments, with relatively few terminations at intervening thoracic levels. These two sets of fibres ('thumb', 'foot') are derived from distinct, separate subareas of motor cortex and pass through exclusive, separate zones of the internal capsule. Thus, developmental contact guidance between somatotopically originating neighbours is inadequate to account for the observed specificity of corticospinal fibre destinations. Fibres must be observing distinctive local segmental cues (perhaps of cytochemical nature) and/or utilising somatotopically distinctive arrival sequencing (i.e. securing specific destinations without neuronal recognition).

Possible removal route of osmiophilic material (lipofuscin) from spinal ganglia of Torpedo marmorata.

The spinal ganglia of Torpedo marmorata have been studied in semithin and ultrathin sections with the view to study the formation and possible mode of removal of lipofuscin. This study suggests that osmiophilic bodies among them lipofuscin originate from degenerating mitochondria. These osmiophilic products concentrate at the neuronal cell border with the satellite cells. The satellite cells have long dense membranous processes which interdigitate, forming a compact myelin sheath but also loosely arranged membranes surrounded by vacuolated plasma. The perinuclear cytoplasmic portion of the satellite cell however contains a rich assemblage of cell organelles well provided for an active metabolism. In this active area which invaginates the neuronal cytoplasm, osmiophilic granules but smaller can be seen, similar to those in the neighbouring neuron. Similar granules are found in cells within the connective tissue space and in the capillary wall. Satellite cells appear not only to be ensheathing cells, providing a perineuronal myelin cover but also capable of removing intra-neuronal debris. It appears that these osmiophilic bodies are taken to the capillary wall by detached satellites or 'handed on' to phagocytes having penetrated between the ensheathing satellites. These cells could take the osmiophilic material to capillaries.

Neuronal regression during ageing: an ultrastructural study of the human cortex.

Neuronal regression has been ultrastructurally investigated in a neuronal sampling of the ageing human cerebral cortex. Even though the number of specimens examined is limited, there is an indication of an age-related regression involving the intraneuronal "nucleus-ribosome system". Such regressive signs are characterized by the polymorphous outline, invagination, reduced size of the nucleus, and in the nucleolar texture. Recognizable changes in the cytoplasm are, alterations in the density and distribution of free ribosomes and in the structure and organization of the rough endoplasmic reticulum cisternae. Furthermore light cytoplasmic areas, and increased number of microtubules and the gradual congestion of the perikaryon by age pigments are reliable criteria for identifying the sequence of morphologic events that occur during neuronal ageing. The above data provide some insight into the neuronal process and adding to a previous proposed model of neuronal maturation.

The time course of synapse formation of mouse neuroblastoma cells in monolayer cultures.

Neuroblastoma cells grown on substrates in culture develop long processes and assume the morphology of normal neurons as judged light microscopically. The development of synapses in the cultured tissue is studied by periodic electron microscopic examination of the areas of contact between cells. The initial explants are free of any apparent synaptic contacts. After 48 h in culture, simple swellings or boutons are detected at the periphery of the cells or at the end of the fine processes. These initial synaptic profiles contain a few vesicles but lack mitochondria. The synaptic vesicles appear to originate from the smooth endoplasmic reticulum. Further explants remain primitive, only the number of vesicles in the cytoplasmic swellings or boutons increases. These clusters of vesicles are 40-60 nm in diameter and morphologically distinguishable from the synaptic vesicles of normal neurons. There are no postsynaptic folds or membrane thickenings. Specialized cell contacts between cells are also present.

Ultrastructural changes in neurons and neuroglia of the avian telencephalon (hyperstriatum accessorium) following tri-ortho-cresyl-phosphate intoxication.

Ultrastructural reactions of neurons of the avian forebrain following tri-ortho-cresyl-phosphate (TOCP) poisoning are described. The neurons show a marked increase in the rough endoplasmic reticulum (RER), with RER specializations such as lamellar bodies and subsurface cisternae, as well as a proliferation of the Golgi complex and neurofilaments. In addition, an increase in the number of dense bodies and mitochondrial osmiophilia is noted. Similar changes can also be observed in the neuroglia. These alterations appear 10-13 days after TOCP ingestion.

Ultrastructural reactions of spinal ganglia to tri-ortho-cresyl-phosphate: effects of neurotoxicity.

The ultrastructure of neurons in spinal ganglia of the domestic fowl poisoned with tri-ortho-cresyl-phosphate (TOCP) shows characteristic changes. The light neurons react to TOCP by a marked increase in the number of neurofilaments. These neurons also contain mitochondria in various degenerative stages. Several of the altered mitochondria show an increasing osmiophilia. Some of the darker neurons display a hypertrophy of the endoplasmic reticulum or a relative increase of neurofilaments. The mitochondria in some of these cells show early stages of degeneration. These changes appear 13 days after TOCP ingestion.

Reacting ultrastructure of the human oligodendrocyte (a study of cerebral cortex distant to brain tumours).

Electron microscopical examination of adjacent human cerebral cortex from patients with brain tumour revealed the following morphological distinctive features of the oligodendrocyte: the presence of a diffuse electron dense material, large quantities of free ribosomes or ribosomal rosettes, eccentric nucleus with irregular clumps of chromatin, swollen perinuclear cisterna, extensive cytoplasmic microtubules, well-developed Golgi apparatus opposite the eccentric nuclei, dilated endoplasmic reticulum and mitochondria. The majority of oligodendrocytes contain large indefinable heterogeneous electron-dense structures within their perikaryon or processes. Oligodendrocytes with similar inclusion bodies are seen in the vicinity of capillaries. For these reasons a possible phagocytic activity of the human oligodendrocyte seems likely.

Annulate lamellae, lamellar bodies and subsurface cisternae in neurons of the avian hyperstriatum accessorium.

Structures identified as annulate lamellae, lamellar bodies and subsurface cisternae were found in neurons of the hyperstriatum accessorium of the avian forebrain. Annulate lamellar arrays with up to six lamellae were present in the larger somata. The lamellae were made up of fused smooth-surfaced cisternae forming pores or annuli and were surrounded by a dense filamentous to granular material. Stacks of nonfenestrated, parallel, regularly spaced cisternae, designated as lamellar bodies, also appeared in the cytoplasm. When flattened they were reminiscent of the electron dense subsurface cisternae. Continuity could be demonstrated between peripherally located subsurface cisternae and lamellar bodies. The dense filamentous to finely granular substance was also located between these structures. Annulate lamellae, lamellar bodies and subsurface cisternae were always observed in conjunction with the rough endoplasmic reticulum. The functional significance of these structural associations is considered.

Surface processes of olfactory receptors.

The free surface morphology of olfactory receptor cells from the nasal mucosa of Cynomolgus monkeys was studied electron microscopically. The receptor cell, in addition to showing characteristic cilia, possess several branched or unbranched shorter elevations or spiny processes covered by numerous delicate lace-like filaments not previously described. These filaments diminish in length and number toward the base of the microvillous protrusions.

The mode of mitochondrial degeneration in gliomas.

Morphologically abnormal mitochondria from human glial tumours are described. For each tumour both the appearances of the mitochondria, and the subsequent mode of degeneration and formation of osmiophilic pigment is characteristic. The significance of these observations is discussed, and it is suggested that the mode of degeneration observed reflects directly a fundamental abnormality in composition compared to normal mitochondria.

Subsurface cisterns in the Cynomolgus retina.

Subsurface cisterns were found in retinal neurons of the Cynomolgus monkey. They were located in amacrine, bipolar and ganglion cells and were associated with the rough endoplasmic reticulum. Subsurface cisterns were not found in Müller cells. The possible functional significance of the subsurface cisterns is discussed.