Golgi preparations as a tool in neuropathology with particular reference to investigations of the human telencephalic cortex.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to H Braak.
Explore the source record for details and available documents.
Light microscopic, histochemical and electron-microscopic studies were made on the brain of a case (No. 1) with Sanfilippo disease, type A. In this case pigment preparations of the isocortex have been demonstrated. Ultrastructural investigations of the skin biopsies (his two male siblings) were also studied (cases 2, 3). Our three siblings of MPS III A, have demonstrated ceroid lipofuscin storage in the brain (case No. 1) and skin biopsies (cases No. 2 and 3) in addition to histological features of MPS. The biochemical studies (enzymatic identification) were made in the cultures of fibroblasts. Also, urine quantitative studies for MPS and N-sulfonate to hexosamino ratio were performed.
Each neuronal type of the human claustrum is differently pigmented. This has been demonstrated by combining a transparent Golgi technique with the specific staining of lipofuscin deposits. One type of projection cells and four varieties of interneurons have been distinguished. In this study the percentage of these different neuronal types has been evaluated using preparations stained for both Nissl material and pigment deposits.
The parastriate borderzone in the human occipital cortex is made conspicuous by clusters of large pyramidal cells in layer III (limen parastriatus gigantopyramidalis: von Economo and Koskinas 1925). Experiments in higher primates provide evidence that the vertical meridian is represented in this region and that these large pyramidal cells connect the parastriate borderzone of both hemispheres via callosal fibres. Golgi preparations of the human parastriate borderzone reveal that the large pyramidal cells generate a stout apical dendrite which gives rise to several side branches in layer III and terminal ramifications in layer II. An unusual feature is that the apical dendrite is almost devoid of spines and that its side branches are only sparsely spined as well. Both the basal and lateral portions of the cell body give rise to spiny dendrites having their domain within layers III and IV. In pigment-Nissl preparations, the large layer III pyramids are marked by coarse and distinct Nissl bodies and a bowel-shaped accumulation of faintly tinged lipofuscin granules located close to the nucleus. Electron micrographs show that up to 30% of the soma membrane are covered by large boutons which make multiple synaptic contacts. This contrasts to the appearance of most other types of cortical pyramydal cells which normally show only a few axo-somatic contacts.
Projection neurons and local circuit neurons of the human lateral geniculate nucleus (LGN) offer different patterns of lipofuscin pigmentation. One type of projection cell (type I neuron) and two varieties of local circuit neurons (type II and type III neurons) can be distinguished on account of their characteristic pigmentation. The majority of the nerve cells are type I projection neurons. Pigmented type II neurons comprise about 8.5% and type III neurons devoid of pigment amount to only 0.2% of the nerve cells.
A characteristic lipofuscin pigmentation permits reliable distinction of the various neuronal types forming thalamic nuclei of the human adult. Type I projection cells with coarse and vacuolated lipofuscin granules are distinguished from type II local circuit neurons with fine and intensely stained pigment and type III neurons devoid of pigment. There is by no means a uniform ratio of projection neurons versus local circuit neurons. A high proportion of local circuit neurons is found in nuclei of the anterior complex, a medium proportion in the specific nuclei of the lateral complex, and a low proportion in the reticular nucleus. The technique and the data provided are being used as a basis for investigations of the diseased human brain.
Nerve cell types of the lateral geniculate body of man were investigated with the use of a transparent Golgi technique that allows study of not only the cell processes but also the pigment deposits. Three types of neurons have been distinguished: Type-I neurons are medium- to large-sized multipolar nerve cells with radiating dendrites. Dendritic excrescences can often be encountered close to the main branching points. Type-I neurons comprise a variety of forms and have a wide range of dendritic features. Since all intermediate forms can be encountered as well, it appears inadequate to subdivide this neuronal type. One pole of the cell body contains numerous large vacuolated lipofuscin granules, which stain weakly with aldehyde fuchsin. Type-II and type-III neurons are small cells with few, sparsely branching and extended dendrites devoid of spines. In Golgi preparations they cannot be distinguished from each other. Pigment preparations reveal that the majority of these cells contains small and intensely stained lipofuscin granules within their cell bodies (type II), whereas a small number of them remains devoid of any pigment (type III). Intermediate forms do not occur.
Nerve cell types of the neocortex-dependent nuclei of the human thalamus were investigated with the use of a transparent Golgi technique, that allows one to study not only the peculiarities of the cell processes, but also the marking characteristics of the intraneuronal lipofuscin pigment deposits. Three principal types of neurons have been distinguished: Type I is a medium-sized to large neuron with a profusely radiating dendrite system. Numerous large vacuolated lipofuscin granules are contained in one pole of the cell body. Type II is a small to medium-sized neuron with a few sparsely branching dendrites. Small and intensely stained pigment granules are dispersed within the cell body. Type III is a medium-sized to large neuron with only a few thick and almost unbranched dendrites devoid of spiny appendages. The dendrites extend over long distances. The cell body is devoid of lipofuscin granules.
In canine ceroid lipofuscinosis (one case studied), isocortical layer IIIab pyramidal cells develop spindle-shaped enlargements of their proximal axon filled with lipopigment, a feature that can be observed in juvenile and adult type of human neuronal ceroid lipofuscinosis and in normal ageing of the human isocortex as well.
The large nerve cells of the granular layer of the human cerebellar cortex have been investigated by means of a newly developed Golgi technique that reveals the pigmentation pattern of individual nerve cells through transparent impregnations of their cell bodies and cellular processes. Three types of large nerve cells have been distinguished: Type I cells correspond to the Golgi cells. They have a rounded or polygonal cell body with only a few dendrites that radiate in all directions. The axon ramifies profusely, close to the parent soma. Cells of this type are most frequently encountered among the large cells of the granular layer. Type I cells contain only a few pigment granules. Type II cells have a fusiform or triangular cell body with a few rather extended dendrites that rarely ramify. Cells of this type are either devoid of pigment or contain a few large pigment granules that can be stained intensely by aldehydefuchsin. Type III cells are multipolar neurons with a fair number of dendrites originating from any point of the soma. The dendrites extend into the deep portions of the molecular layer. Here and also within the Purkinje cell layer they repeatedly branch off forming a dense dendritic arborization. Cells of this type are evenly distributed throughout the entire granular layer and throughout the adjacent portions of the Purkinje cell layer and the white matter as well. Type III cells are filled with tightly packed lipofuscin granules. The pattern of pigmentation is characteristic for each of these neuronal types. The three types of large nerve cells within the granular layer of the human cerebellar cortex can therefore be distinguished not only in Golgi impregnations but also in pigment-Nissl preparations.
The amount of myelin in Gennari's stripe in the human striate cortex has been measured in normal individuals ranging in age from 18 to 96 years. From the third decade onward, the amount of myelin in this intracortical plexus is gradually reduced with advancing age.
A parcellation of the human basolateral amygdala is given on the basis of pigmentoarchitectonic analysis. Examination of Golgi preparations and deimpregnated preparations counterstained for lipofuscin pigment revealed three classes of nerve cells: Class I neurons generate a stout main dendrite from one pole of the cell body and several minor ones from the base opposite to the main process. The dendrites are covered with spines. The axon follows a straight course and gives off numerous collaterals. Class I neurons in the lateral and accessory basal nucleus contain finely granulated and widely dispersed pigment. Cells located in the basal nucleus store a large amount of pigment, concentrated at one pole of the cell body. The small class I neurons in the granular nucleus and the intercalated cell masses are marked by large vacuolated pigment granules. Class II neurons have smoothly contoured or sparsely spined dendrites. Size and shape of their cell bodies vary. They contain a large amount of course and intensely stained lipofuscin granules. Class III neurons display similar features in the Golgi preparation but their cell bodies are devoid of pigment. A frequently occurring type is a tiny cell with thin dendrites and profusely branching local axon. Each of the different classes of neurons shows a characteristic pattern of pigmentation. Therefore, Nissl preparations combined with a pigment staining technique, offer the particular advantage of distinguishing the spine-laden neurons from sparsely spined or aspinous types.
A case of Niemann-Pick disease was examined with Golgi preparations and a transparent Golgi impregnation counterstained for intraneuronal pigment deposits. There was a specific type of storage of unmetabolized substrate restricted to certain nerve cell types. The most conspicuous changes in the isocortex were: 1) dilated axonal segments in layer IIIab pyramidal cells filled with storage material; the volume of these axonal expansions often exceeded that of the soma; 2) distension of layer IIIc, layer V, and layer VIa pyramidal cell perikarya with storage material; 3) new formation, elongation, and vertical orientation of basal dendrites in layer V pyramidal cells; 4) well-preserved pyramidal cells almost devoid of storage material and generally small in size were frequently found in layers II and IV, and to a lesser extent in layers III, V, and VI; 5) severe numerical reduction of small pigment-laden stellate cells in layers II and III; and 6) reduction of stellate cells devoid of lipofuscin pigment. These cells only occasionally contained small amounts of storage material.
A method is described by which the precipitate that normally fills impregnated cells in Golgi preparations is confined to a thin and transparent scattering of fine particles that defines the somata and cellular processes. The coating is stable enough to withstand counterstaining and thus makes possible direct evaluation of structural features not only of cellular processes but also of cytoplasmic components.
Golgi preparations reveal the existence of two classes of nerve cells in the human dentate nucleus. Relatively large principal cells predominate. Small local circuit neurons are scattered throughout the nuclear gray. By means of a newly developed de-impregnation technique the pattern of pigmentation of both cell types can be studied. The principal cells show a considerable amount of finely granulated and faintly tinged pigment, whereas the local circuit neurons contain only a few large and intensely stained lipofuscin granules. The local circuit neurons give off a few smoothly contoured and rather extended dendrites. The axon is generated from either the cell body or a dendrite by way of a cone-shaped initial portion. A thin thread-like segment follows. Further distally, the caliber of the axon increases abruptly. This thick portion branches off several times at short intervals giving off fine processes with bead-like enlargements. Occasionally, a second axon is generated from these cells.
Most of the precipitations that normally fill up Golgi impregnated nerve cells can easily be removed by placing the material in a diluted solution of ammonia for several hours. A very fine scattering of electron-dense particles remains. Preparations processed in this way can be studied electron microscopically, in this way rendering fine structural examination of previously identified neurons possible. The method is applicable for silver chromate Golgi techniques and can be used for all parts of the brain.
Nerve cells of the human striatum were investigated with the use of a newly developed technique that reveals the pattern of pigmentation of individual nerve cells by means of transparent Golgi impregnations of their cell bodies and processes. Five types of neurons are distinguished: Type I is a medium-sized spine-laden neuron with an axon giving off a great number of collateral branches. The vast majority of the cells in the striatum belong to this type. Numerous intensely stained lipofuscin granules are contained in one pole of the cell body and may also extend into adjacent portions of a dendrite. Type II is a medium-sized to large neuron with long intertwining dendrites decorated with spines of uncommon shape. A distinguishing feature of this cell type is the presence of somal spines. This cell type is devoid of pigment or contains only a few tiny lipofuscin granules. Type III is a large multipolar neuron. The cell body generates a few rather extended dendrites that are very sparsely spined. The finely granulated pigment is evenly dispersed within a large portion of the cytoplasm. Type IV is a large aspiny neuron with rounded cell body and richly branching tortuous dendrites. The axon branches frequently in the vicinity of the parent soma. Large pigment granules are concentrated within a circumscribed part of the cell body close to the cell membrane. Type V is a small to medium-sized aspiny neuron. The dendrites break up into a swirling mass of thin branches. More than one axon may be given off from the soma. The axons branch close to the soma into terminal twigs. Cells of this type contain numerous large and well-stained lipofuscin granules. Each of the cell types has a characteristic pattern of pigmentation. The different varieties of nerve cells in the striatum can therefore be distinguished not only in Golgi impregnations but also in pigment-Nissl preparations.
Neuronal types of the human claustrum have been investigated by means of a transparent Golgi technique which enables one to study the characteristics of not only the cellular processes but also the marking features of the nuclei, the cellular organelles, and the paraplasmic substances of various types of nerve cells. Five varieties of neurons have been distinguished: Type I represents a class of spiny nerve cells varying to a certain extent in size and shape. These cells contain fine and widely dispersed lipofuscin granules which can only faintly be tinged by aldehydefuchsin. Type II cells are large aspiny neurons. Their cell bodies contain a great number of deeply stained coarse pigment granules. Type III cells are large aspiny neurons devoid of pigment deposits. Type IV is a small pigment-laden aspiny neuron. Type V is a small aspiny neuron devoid of lipofuscin granules. The pattern of pigmentation revealed by the different types of nerve cells turns out to be highly characteristic. It can well be used for classification of the various types of nerve cells which occur within the reaches of the claustrum.