Early Stages Of Degeneration Research Articles

Electron microscopy of degenerative changes in decentralised rat superior cervical ganglia

Decentralised rat superior cervical ganglia and their contralateral control ganglia were excised at intervals of 2hr to 9wk after preganglionic nerve section, fixed in veronal-acetate buffered osmium tetroxide and prepared for electron microscopy. Degenerative changes were observed first at 11hr and were widespread at 24hr. These changes consisted of clumping and/or reduction in number of the synaptic vesicles with their lysis, mitochondrial alterations, separation of the pre- and post-synaptic membrances, breakdown of the axoplasmic and surrounding Schwann cell membranes and digestion of the degenerating material, probably by the Schwann cells (‘Resolution’). Degenerating structures were observed less frequently at 3 days that at 24hr and were scarce by the seventh day after decentralisation. A few synapses at an early stage of degeneration were observed in the seventh day specimens. Most of the few unaltered presynaptic terminals found 7 days after decentralisation contained small (adrenergic-type) granular vesicles, and may have represented adrenergic connections between ganglion cells. The number of these connections may have increased since the 3rd day after decentralisation.

Electron microscopic studies of Wallerian degeneration in rat optic nerves. I. The multipotential glia.

AbstractThe development of phagocytes has been studied with the electron and light microscopes in rat optic nerves undergoing Wallerian degeneration. The postoperative survival times ranged from five hours to 250 days. This paper focuses on cells that have been designated either as multipotential glia or as a third neuroglial cell type. Such cells increase markedly in number during the first several weeks of nerve fiber degeneration while the populations of astrocytes and oligodendrocytes remain relatively stable. During this early stage of degeneration, multipotential glial cells develop very irregular shapes and have many processes and complex folds that intermingle with the degenerating nerve fibers. These cells engulf myelin fragments and nerve fibers which become enclosed within vacuoles that show acid phosphatase reaction product in specimens prepared for cytochemistry. The debris containing vacuoles can therefore be considered as phagolysosomes. In addition, the multipotential glial cells show an increase in the number of lipid inclusions over that of cells in normal material. Eventually some multipotential glial cells accumulate large quantities of lipid inclusion and come to resemble the “Gitter” cells described in classical neuropathological studies.The numerical and cytological changes occurring within the multipotential glial population indicate that these cells are an important source of phagocytes in the type of lesion which we have studied. The breakdown of degenerating myelin by multipotential glial cells, the origin of these cells and their relationship to the microglial cells stained in light microscopic preparations are discussed in detail.

Effect of Cortisone on the Establishment of Nippostrongylus brasiliensis in the Rabbit

The present investigation has shown that neither the cortisonenor saline-treated rabbit is a satisfactory host for the maintenance of Nippostrongylus brasiliensis. In the saline-treated rabbit, this is due primarily to an inflammatory reaction that occurs in the skin and leads to subsequent nodulation of the infective larvae. Cortisone did suppress the rabbit's inflammatory skin response and a greater number of larvae were able to complete the skin-lung and lung-intestine migrations and become established as adults. However, the majority of larvae recovered from the lungs had failed to undergo the third molt and there was an extension of the worm prepatent period. In addition, other factors (undetermined) appear to prevent the larvae from undergoing normal development in the skin and lungs. There was no stunting of adult worms in the intestine of the rabbit and eggs recovered from feces were viable. Male worms were more numerous than females over a 10-day period postinfection. Thorson (1953) reported that the rabbit is a highly refractory abnormal host to Nippostrongylus brasiliensis (Travassos, 1914). Further experimental evidence concerning this host-parasite relationship could not be found in the literature. In our laboratory, previous experiments established that in young rabbits (8 weeks of age) an effective resistance develops, or exists, against the successful migration of inoculated N. brasiliensis larvae. Only 0.03% of these larvae completed migration from skin to intestine as compared to an average of 90% (Haley, 1962b) in the rat (the normal host). Skin sections from rabbits 40 hr postinfection (PI) showed low-grade inflammation beginning to localize around the larvae, with defensive cells (mononuclear and polymorphonuclear) migrating toward the larvae. Skin sections from rabbits 3 days PI revealed that the larvae were coiled and surrounded by an intense inflammatory response preceding encapsulation. In skin sections from rabbits 6 days PI, completely formed nodules around larvae were evident and the larvae were in early stages of degeneration. The results obtained are similar to those reported by Parker (1961) for the guinea pig. During recent years there have been several reports on the effect of cortisone on N. braReceived for publication 6 June 1969. * Based in part on a thesis submitted to the Graduate School, Kent State University, in partial fulfillment of the requirements for the Master of Arts degree. siliensis in the rat (Weinstein, 1953, 1955; Ogilvie, 1965). Reports on the effect of cortisone on N. brasiliensis in certain abnormal hosts, ground squirrel and guinea pig, have also been published (Cross, 1960, 1964; Parker, 1961). These authors concluded that cortisone had a suppressive effect on the host's cellular response. The work herein reported deals with the treatment of rabbits with cortisone to determine if it would suppress the cellular response and, as a result, permit a greater number of worms to reach maturity in the intestine. MATERIALS AND METHODS

Wallerian degeneration in the optic nerve of a reptile: an electron microscopic study.

AbstractNumerous optic nerve fibers persist for a period of up to 20 months following enucleation in reptiles, although it is unlikely that a significant number of efferent fibers are present. After varying survival periods, almost all nerve fibers display distinct morphological changes probably associated with degeneration, but most features previously associated with early stages of degeneration can be seen in long‐survival material except for the early and rapid loss of all non‐myelinated fibers and a honeycomb tubular degeneration associated with the inner and outer myelin layers. Distinct sequential stages of axon and myelin degeneration could not be ascertained despite the slow rate of degeneration in poikilotherms. The varieties of abnormal axon morphology are documented and considered in terms of current light microscopic staining methods.

EFFECT OF SHORT-TERM VITAMIN A DEFICIENCY ON TESTICULAR LIPIDS IN THE RAT

In 1933, Mason reported that long-term vitamin A deficiency caused sloughing of seminiferous tubular elements of the rat testis. Since that time, several workers have reported testicular lesions caused by deficiency of the vitamin (Beaver, 1961; Coward, McHowell, Pitt & Thompson, 1966; Gamball, 1966). Gamball (1966) found changes in testicular phospholipid associated with sterility following vitamin A deficiency. Since other treatments which result in sterility also cause lipid changes in the testis (Fleeger, Bishop, Gomes & VanDemark, 1968; Johnson, VanDemark, Gomes, Butler & Hodgen, 1967), it is possible that testicular lipids reflect the status of the testis, even during early stages of degeneration following deleterious treatments. The present study was undertaken to determine whether testicular lipid levels are affected by short-term vitamin A deficiency and, if so, the nature of such changes. Male Wistar rats, 30 days of age, and weighing about 100 g, were fed a commercially available (Nutritional Biochemicals Corporation, Cleveland, Ohio 44128) rat diet, purported to be vitamin A free, for 5 weeks. Control animals were supplemented with 12 i.u. retinol/g of feed to meet the vitamin A requirement. A body-weight plateau, considered the first sign of deficiency,

An experimental electron microscopical study on the mode of termination of cerebellar corticovestibular fibres in the cat lateral vestibular nucleus (Deiters' nucleus).

The present paper is an experimental study on the mode of termination of cerebellar corticovestibular fibres in the cat. The distribution of degenerating terminal structures as this appears in electron micrographs of eight animals with a survival time from three up to eleven days is described. The early stage of degeneration of Purkinje cell axons is a filamentous reaction during which fibres as well as boutons are enlarged and filled with filaments. The initial reaction is followed by shrinkage, and many fibres and boutons are at the 4 day stage electron dense, and no filaments can be recognized. Other fibres and boutons show intermediate stages of degeneration. Only dark degenerating axons and boutons are present at the 11 day stage. The observations are related to those made in other nuclei and regions where degeneration has been described in electron micrographs. Degenerating terminal myelinated fibres ending with terminal and en passage boutons are found. An attempt is made to correlate the findings with those made in normal animals and in Golgi sections. The mode of termination and the pattern of branching of Purkinje cell axons are discussed. The degenerating terminal structures are in synaptic contact with cells of all sizes and with all parts of the neurons, i. e., soma, proximal and distal dendritic trunks and spine-like projections. Elongated and rounded synaptic vesicles are present in the degenerating boutons. The glial reaction adjacent to degenerating boutons is also described, and brief mentioning is made of findings in the intracerebellar nuclei of the same animals. The findings in these nuclei are essentially the same as those made in the lateral vestibular nucleus.

Microincineration of Degenerating Anterior Horn Cells in Experimental Poliomyelitis.

The literature concerned with poliomyelitis seems to be largely composed of results of studies on the more general and gross pathological aspects of the disease. Another line of investigation has been opened up by Marinesco, Policard and Cowdry which begins with the cell rather than the symptom. As yet, no such approach has been made toward the understanding- of poliomyelitis. The present paper deals with but a single phase of the cytopathology of the disease—the changes in inorganic constitution as determined by the microincineration method. The material was obtained from autopsies of 43 monkeys (Maeacus rhesus) experimentally infected with poliomyelitis by the intracerebral and intranasal routes. The tissues were fixed in absolute alcohol formalin and prepared for incineration according to the method described by Scott. Alternate serial sections were incinerated or were stained with hematoxylin and eosin in such a manner that colored and ashed preparations of the same cell were available for comparison. For controls, similarly prepared material from 10 normal monkeys or monkeys dying of diseases other than poliomyelitis was used. The normal anterior horn cell incinerated under optimum conditions leaves a characteristic and uniform ash. The cytoplasm is represented by a very finely divided, mist-like, bluish or whitish ash. Against this filmy background spots of somewhat denser whitish, powdery material may usually be seen, evidently representing the Nissl bodies. The nucleus appears as a hole in the cell, set here and there with refractile granules, sometimes yellowish, but more often white, which may be identified as the chromatin substance. The mineral residue of the nucleolus is seen as a flat white, finely granular material of varying intensity. In the spinal cord of a monkey inoculated with poliomyelitis virus, several forms of degenerating cells may be seen. Three typical pictures will be described here: 1. During the early stages of degeneration the cell becomes somewhat swollen, the Nissl bodies are lost and the cytoplasm tends to take a lighter stain. The nucleus is often enlarged and may occupy an excentric position in the cell body.

A HISTOLOGICAL STUDY OF THE TESTIS IN CASES OF PSEUDO‐INTERSEXUALITY AND CRYPTORCHISM WITH SPECIAL REFERENCE TO THE INTERSTITIAL CELLS

1. A histological study was made of the testes of two intersexual pigs, and the inguinal cryptorchids of a rabbit, five two‐years old horses, and a cat.2. (a) Enormous hyperplasia and (especially in Pig II) considerable hypertrophy of the interstitial cells are seen in the case of the pigs, whilst the seminiferous tubules are small, and lined by a single layer of cells undergoing fatty degeneration.(b) In the testis of the rabbit the tubules are lined by germ and Sertoli cells, many of the former being in mitosis. Spermatocytes in various stages of synapsis are found and many of the tubules contain spherical colloid bodies. Leydig cells are present in large quantities and are undergoing hypertrophy, the various stages of which can be followed.(c) The tubules of the ectopic testes of the horse are somewhat reduced in size and contain spermatogonia, Sertoli cells and spermatocytes. The interstitial cells show marked hyperplasia.(d) The inguinal testis of the cat is a normal immature organ. Some of the tubules show early stages of degeneration and contain small colloid bodies. Secondary spermatogonia are conspicuous but there are no spermatocytes. The interstitial tissue is normal and shows no hyperplasia.3. To account for the variation in the quantity of the interstitial cells in the above cases, it is assumed that they have a dual rôle and are both trophic and endocrine.4. Evidence of a trophic function is as follows :(a) Fat globules and lipoids are common in the Leydig cells.(b) In the development of the testis there is an alternation of growth between the tubules and the interstitial tissue, suggesting that the latter act as a food‐reserve for the former.(c) In work on the testis of hibernating animals hyperplasia and hypertrophy of the interstitial cells are found to occur in spring and fat‐globules appear in the cytoplasm — again indicating that the Leydig cells store up food‐material on which the germ‐cells can draw during spermatogenesis.5. To maintain physiological equilibrium in the testis, there must be a balance between food‐material passed in by the blood‐stream and food material consumed by the germ cells.6. In cryptorchism this balance is upset owing to degeneration of the seminal epithelium and the interstitial cells absorb food of which they can no longer dispose.7. Hyperplasia of the interstitial cells takes place in order to equalize intake and consumption and so restore physiological equilibrium.8. The extent of this hyperplasia depends on two main factors :(a) The metabolic condition of the individual. In the pig with its low energy output and strong tendency to store food material in the tissue, hyperplasia is immense. In inactive individuals such as the pig and tame rabbit, the cells finally undergo hypertrophy owing to accumulation of food material in the cytoplasm. This is followed by secretory inactivity resulting in intersexual secondary sexual characters (Pig I). In a very active animal the food reserve in the body will be heavily taxed and nutritive material destined for an organ which no longer functions will tend to be reabsorbed and utilised elsewhere. The Leydig cells will thus receive little more than is requisite for their own wants, hyperplasia will be correspondingly slight and thus endocrine activity will be unimpaired.(b) The degree of degeneration of the seminal epithelium. In the pig, there is complete degeneration and enormous hyperplasia, while in the cat there is slight degeneration and no hyperplasia.9. Data are insufficient to throw any light on the problem of pseudo‐intersexuality.