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Biomedical subjects

J Zimmer

Publications and source records attributed to J Zimmer.

At least 181 records · Page 10Linked to original sources

Transplantation of central nervous tissue. An introduction with results and implications.

Studies of post-lesional reorganization of central nervous connections have shown that central nerve fibers respond to nearby denervation by sprouting and formation of new terminals. The connections in the central nervous system (CNS) are accordingly much more plastic than was thought for a long time. This has revived the interest in transplantation of central nervous tissue. In this study we present some historical data on CNS transplantation supplemented by recent results obtained in our laboratory. Pieces of hippocampal tissue from embryonic or early postnatal rats were transplanted to different parts of the brain of littermates or adult rats. About two-thirds of the transplants were recovered after survival times ranging from 4 d to 2 years, and their cytological organization and intrinsic connections were monitored by cell and fiber stains and histochemical methods (AChE staining and Timm sulphide silver method). Comparison with both a normal and a lesioned control material revealed that in most transplants the tissue had developed as it does when left in situ in the donor brain, but deprived of its major afferent connections. In several instances we found evidence of a major exchange of connections between the transplants and host brains. The conditions needed for this to occur appeared to involve growth stimulation of host brain fibers by transection (host to transplant) and denervation of host neuropil (transplant to host). In cases where these conditions are met, the use of transplants may have future implications in attempts to repair lesions in the central nervous systems.

Animals↗

Quantitative electron microscopic evidence for reinnervation in the adult rat interpeduncular nucleus after lesions of the fasciculus retroflexus.

The method of electron dense degeneration has been used to make a quantitative study of the projection from the habenula through the fasciculus retroflexus (FR) to the interpeduncular nucleus (IPN) in the rat. The IPN si a midline structure onto which the right and left fasciculi converge. In the rostral part of the IPN the fascicular axons from each side form synapses throughout the mediolateral extent of the ventral two-thirs of the nucleus. In the caudal part of the IPN the fascicular axons from each side terminate to an equal extent in two discrete, parasagittal zones, situated one on side in the mid-mediolateral extent of the IPN. These zones contain clusters of neurons located along the course of a characteristic row of arterioles and venules penetrating the IPN from its ventral surface. In both rostral and caudal parts of the IPN the fascicular axons form single synaptic contaerpeduncular neurons, but caudally, in the two parasagittal zones they also form crest synapses. Crest synapses are only found in this part of the IPN. In crest synapses two presynaptic terminals form markedly asymmetrical contacts with the parallel opposing sides of an attenuated dendritic appendage (the crest). After unilateral fascicular lesions only one member of a pair of axon terminals contacting a crest degenerates. After bilateral fascicular lesions, however, there are many instances in which both members of a crest pair degenerate. This indicates that the axon terminals from the right and left fasciculi are segregated at the level of the crests, in such a way that one terminal comes from the right fasciculus and one from the left. At longer survivals after unilateral or bilateral fasciculus lesions the degeneration is completely removed, but crest synapses are still present, indicating that the presence of fascicular axons is not necessary for the maintenan ce of crests in the IPN. To investigate the effects of chronic deafferentation, the left fasciculus was destroyed and, after a survival of at least six weeks (sufficient for all degeneration to be removed) the right fasciculus was destroyed one day before killing. Under these conditions there are many crests in which both axon terminals show degeneration. The proportion of such doubly degenerating crest synapses is similar to that found after acute (1 day) bilateral lesions, indicating that axons from the right fasciculus have reinnervated sites formerly occupied by the left fasciculus. We conclude that during normal development there is some constraint which prevents both sides of a crest being innervated by axons from the fasciculus of the same side of the brain, but that this constraint is not effective after unilateral fascicular lesions in the adult.

Afferent Pathways↗

Laminar differentiation of the hippocampus, fascia dentata and subiculum in developing rats, observed with the Timm sulphide silver method.

The laminar staining of the rat hippocampal region with the Timm sulphide silver method is from studies on adult rats known to depend on the various fibersystems terminating in these laminae. In order to illustrate the development of these fibersystems the laminar differentiation of the Timm staining of fascia dentata, hippocampus and subiculum is presented for rats between 1 and 31 days old. Corresponding changes in cytoarchitectonics as revealed by thionin staining are briefly demonstrated. Even on the first postnatal day there are indications of the mature, laminar staining pattern, and between three and nine days all the laminae corresponding to the terminal fields of the major afferent and intrinsic systems appear. After 12 days only minor additions to the laminar pattern develop, but there are adjustments of absolute and relative dimensions of layers and fields, and also the staining densities of individual laminae change. These observations are in good correlation with the available information on both hippocampal neurogenesis and cytodifferentiation, and the few fiber tracing studies performed on the developing hippocampal region. Compared to the latter, which ideally marks only one system or one lamina per animal, the Timm method provides an excellent means for getting an overview of the general developmental situation at the different ages. Thus developmental gradients along septotemporal, medio-lateral and basal-apical axes are found; which should be heeded in future studies on hippocampal synaptogenesis. The observations are discussed in relation to current models for neuronal growth and formation of nervous connections.

Animals↗

An improved Timm sulphide silver method for light and electron microscopic localization of heavy metals in biological tissues.

Modifications of the Timm sulphide silver method for the demonstration of heavy metals are described. To improve the structural preservation of the tissues perfusion with a glutaraldehyde fixature is employed before perfusion with the sodium sulphide solution. For the subsequent staining for light and electron microscopy, procedures for plastic embedding, paraffin embedding and cryostat sectioning are presented. Examples from several tissues are shown, including the pituitary, pancreas, intestine, tongue, kidney, testis and brain. The staining of autolytic, postmortal human brain tissue is demonstrated.

Animals↗

Ventricular opacification after intravascular injections of contrast material.

The cerebral ventricles of two neonates were demonstrated on CT scans and plain radiographs after the intra-arterial injection of contrast material. Leakage of contrast material into the ventricles after intravenous injection probably indicates damage of the blood-brain barrier. Breakdown of this barrier results only from severe and prolonged anoxia because cerebral vessels are much more resistant to anoxia than neuronal tissues. The authors have not observed ventricular opacification in adults.

Cerebral Ventriculography↗

Laser UV microirradiation of interphase nuclei and post-treatment with caffeine. A new approach to establish the arrangement of interphase chromosomes.

Laser UV microirradiation of Chinese hamster interphase cells combined with caffeine post-treatment produced different patterns of chromosome damage in mitosis following irradiation of a small area of the nucleus that may be classified in three categories: I)intact metaphase figures, II)chromosome damage confined to a small area of the metaphase spread, III)mitotic figures with damage on all chromosomes. Category III might be the consequence of a non-localized distortion of nuclear metabolism. By contrast, category II may reflect localized DNA damage induced by microirradiation, which could not be efficiently repaired due to the effect of caffeine. If this interpretation is right, in metaphase figures of category II chromosome damage should occur only at the irradiation site. The effect might then be used to investigate neighbourhood relationships of individual chromosomes in the interphase nucleus.

Animals↗

Crossed pathways from the entorhinal area to the fascia dentata. I. Normal in rabbits.

The entorhinal area projects to the Ammon's horn and the fascia dentata by way of the medial and lateral perforant paths that originate in the medial and lateral part of that area, respectively. The two tracts terminate at different laminar levels in the molecular layers of the ipsilateral hippocampal regio inferior and fascia dentata. Using the Fink-Heimer technique, each of the perforant paths in the normal rabbit is now shown to innervate the antero-dorsal extremes of the Ammon's horn and fascia dentata in both hemispheres. The crossed and uncrossed components of each path innervate homotopic zones on each side. This bilateral innervation contrasts with the situation in the rat where only very weak crossed components exist. Degeneration particles in the fascia dentata contralateral to a lesion of the perforant paths diminish in number along the course of the fibers as they proceed away from the midline, but are traceable for several millimeters. Crossed fibers are shown to pass from one hemisphere into the other directly through the fused molecular layers of the fasciae dentatae. The bilateral innervation in the rabbit indicates that even though the axons of the perforant paths are highly specific with respect to the class of neuron and the dendritic segments upon which they form synapses, they apparently do no possess a mechanism by which they can distinguish between the receptive fields in the two hemispheres. It is concluded that during ontogeny the perforant path fibers from both sides most likely compete for available synaptic sites in the rostral part of their terminal fields and that their relative amounts in the two hemispheres is governed by spatial and temporal factors.

Animals↗

Crossed pathways from the entorhinal area to the fascia dentata. II. Provokable in rats.

In the rat thhe perforant pathways from the entorhinal area normally innervate the fascia dentata only ipsilaterally. However, unilateral ablation of the entorhinal area (deentorhination) induces the formation of an anomalous crossed projection from the intact contralateral entorhinal area to the septal portion of the deafferented fascia dentata. After deentorhination of rats aged 1-30 days the organization of this projection was analyzed (a) by producing secondary lesions in the intact entorhinal area of perforant paths and observing the results anterograde degeneration with Fink-Heimer silver impregnation techniques, and (b) by staining with Timm's sulfide silver method whichmakes the terminal fields of afferent systems stand out in different tones of colors. Both methods showed the crossed entorhino-dentate projection to consist of two separable components. They were named the crossed medial perforant path and the crossed lateral perforant path, corresponding to their similarity in origin, dendritic localization of termination and Timm stainability to the ordinary, uncrossed medial and the lateral perforant pathways (MPP and LPP) which arise in the medial and lateral parts of the entorhinal cortex, respectively. Similarly induced crossed projections were demonstrated to the subcallosal continuation of fascia dentata, the fasciola cinerea. The heaviest terminal field of the crossed entorhino-dentate projection which was found in the most rostral and medial parts of the deafferented fascia dentata correlated with a lack of expected aberrant extension into theMPP and LPP terminal zones of commissural and ipsilateral hippocampodentate fibers. In Fink-Heimer preparations there was little variation in the distribution of the aberrant crossed sustems over the range of ages studied although the chronic operations performed earliest postnatally (5 days) tended to produce the heaviest representation. This latter observation appeared consistent with changes in the Timm staining pattern of the deafferented fascia dentata, since with an increase in age at the primary lesion from 5 to 14 days there was no increase in the spread into the fascia dentata of Timm stainable axon ter minals from CA3, interpreted as a sign of fewer crossed entorhinal afferents succeeding in a presumable competition with the CA3-derived system for available terminal space.

Age Factors↗