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Biomedical subjects

J Sievers

Publications and source records attributed to J Sievers.

At least 73 records · Page 4Linked to original sources
PubMed1985

Meningeal cells are involved in foliation, lamination, and neurogenesis of the cerebellum: evidence from 6-hydroxydopamine-induced destruction of meningeal cells.

In the present paper we report on experiments conducted to find out if there is a positive correlation between the destruction of meningeal cells over the newborn rat cerebellum by 6-hydroxydopamine (6-OHDA) and the subsequent development of abnormalities in cerebellar fissuration, lamination, and granule cell number. Both destruction of meningeal cells and quality and magnitude of 6-OHDA-induced cerebellar defects show the same threshold sensitivity without further dose responsiveness. Blockade of neuronal uptake 1 for catecholamines with nomifensine prevents neither destruction of meningeal cells nor the development of abnormalities in cerebellar structure after 6-OHDA treatment. Blockade of extraneuronal uptake 2 for catecholamines with normetanephrine prevents both destruction of meningeal cells and the development of typical cerebellar abnormalities after 6-OHDA treatment. All three parallel experiments suggest that there is a positive correlation between the destruction of meningeal cells and the development of abnormal cerebellar structure, indicating that meningeal cells are involved in these defective morphogenetic processes, i.e., fissuration, lamination, and cell proliferation in the external granular layer. The preferential localization of defects in cerebellar fissures indicates that, in analogy to the mesenchyme surrounding other epithelia with a branching morphogenesis, the role of meningeal cells could be the production of interstitial collagen which is necessary to stabilize the epithelial basal lamina in the fissures.

Animals↗
PubMed1984

The injury response of nerve fibres in the anterior medullary velum of the adult rat.

The injury response of myelinated central nervous system (CNS) axons was documented in the anterior medullary velum (AMV) of the adult rat. Study of silver-stained AMV whole-mounts revealed sprouting of injured axons as early as 14 h post-lesion (hpl), with a complex network of fibres formed by 48 hpl. Signs of fibre degeneration were also apparent from 48 hpl, increasing in extent until 15 days post-lesion (dpl). Fragmentation was largely confined to specific fibre bundles, constituted by the distal portions of severed axons. Although some degeneration of regenerated axons was evident from 15-20 dpl, many remained intact beyond this time, particularly in the area adjacent to the exit of the trochlear nerve, where most regenerated fibres penetrated the ipsilateral trochlear nerve. Counts of HRP filled neurons in the trochlear nucleus after injection of the superior oblique muscle showed that axons entering the IVth nerve rootlet were exclusively ipsilateral trochlear fibres. Less than 50% regenerated; most other severed axons degenerated. The few axons remaining in the AMV may have been fibres, undamaged by the original lesion, which normally course longitudinally through the ipsilateral AMV. These results show that IVth nerve fibres preferentially enter IVth nerve rootlets and, in so doing, survive the effects of injury. Most other CNS axons in the AMV which do not enter the trochlear root probably degenerate.

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PubMed1984

6-Hydroxydopamine induced ectopia of external granule cells in the subarachnoid space covering the cerebellum. II. Differentiation of granule cells: a scanning and transmission electron microscopic study.

The present report describes the morphological differentiation of ectopic granule cells from external granule cells that have been induced to escape from the cerebellar cortex into the subarachnoid space by injecting neonatal rats with 100 microgram 6-hydroxydopamine (6-OHDA) into the cisterna magna. The following cell types were observed in the period between 5 and 25 days postinjection (dpi): (1) unipolar cells with one process bearing a growth cone at its tip; (2) bipolar cells with two thin beaded processes originating from opposite cell poles, bearing growth cones at their tips; (3) bipolar cells with a T-like process at one pole and a short process lacking a terminal growth cone at the opposite pole; (4) multipolar cells with one thin beaded process and two or more short processes bearing growth cones of a different morphology at their tips; (5) intermediate stages. In the late second week p.i., cell aggregates were observed that continually increased in size up to 30 dpi. On the basis of our light, transmission, and scanning electron microscopic findings, we interpret these cell types to be equivalent to the individual stages of granule cell differentiation that characterize axon formation, migration, and aggregation. In the period between 30 and 365 dpi, granule cells were almost exclusively organized into cell colonies of different sizes, but small cell clusters and single granule cells exhibited the scanning electron microscopic features of adult granule cells, i.e., a small spherical cell body, a single axon with parent axonal stem, T-junction, and parallel fiber, and dendrites engaged in synaptic glomeruli. The parallel fibers ran in fasciculi of different sizes, often parallel to each other, but without preferential orientation over the cerebellar surface. During migration and aggregation, the granule cells and their processes were associated with a substrate of glial sheets that in turn were connected to intracortical Bergmann glia fibers. Our findings indicate that (1) granule cells differentiate normally in an ectopic environment in the presence of glia, (2) ectopic Bergmann glia contain no directional information to guide aberrant migratory granule cells to their correct destination, (3) granule cells can survive outside the brain parenchyma for periods up to one year (the longest postinjection interval studied).

Animals↗
PubMed1984

A quantitative comparison of the reactions of retinal ganglion cells to optic nerve crush in neonatal and adult mice.

The response of neurons and glia of the ganglion cell layer of the retina to optic nerve crush was studied in adult and neonatal albino mice between 10-85 days post-lesion (dpl). The numbers of ganglion cells and glia surviving optic nerve transection were quantified using Nissl-stained retinal whole mounts. Large- and intermediate-sized ganglion cells were more sensitive to axotomy in the optic nerve than small-sized cells. About 80% of the former cells degenerated by 10 dpl in adult mice whilst 90-100% were affected in neonates. 40-60% of the small-sized ganglion cells survived in adults whilst in neonates, although a similar number escaped the effects of axotomy at 10 dpl, by 30 dpl only less than 10% remained. These aspects were reflected in the changes in the relative frequency distribution with time of ganglion cells in normal and lesioned mice. No significant alterations in glial cells in the ganglion cell and fibre layers of the retina were recorded at any time of lesioning the optic nerve.

Age Factors↗
PubMed1984

A qualitative comparison of the reactions of retinal ganglion cell axons to optic nerve crush in neonatal and adult mice.

The reaction of ganglion cell axons in the mouse retina to optic nerve crush was studied in adult and neonatal albino mice 10-85 days after operation, using silver-stained retinal whole mounts and sagittal sections of retina and optic nerve. In both adult and neonatal animals the majority of neural cells and axons degenerated; surviving neurons had small cell bodies. Degeneration was more marked in neonatal neurons compared to adult neurons. In the adult study, two populations of axonal sprouts growing from the ends of the severed ganglion cell axons were identified. One population, representing the large majority of fibres grew for up to 20 days after operation in the myelinated retinal stump of the optic nerve and then degenerated. A smaller number of axons grew for the whole duration of the study, initially in the inner plexiform area juxtaposed to the non-myelinated optic nerve head and peri-papillary region of the retina, but later invaded the entire retina. In the neonate, no evidence of axonal regeneration was seen, although transient axonal collateral sprouting of surviving ganglion cells occurred.

Age Factors↗
PubMed1983

Distribution of tritium label in the neonate rat brain following intracisternal or subcutaneous administration of [3H]6-OHDA. An autoradiographic study.

The present report describes the distribution of tritium label after injection of newborn rats with [3H]6-hydroxydopamine ([3H]6-OHDA). The animals were injected either intracisternally (i.c.) or subcutaneously (s.c.), with or without pretreatment with nomifensine, which blocks the high-affinity uptake of both noradrenaline (NA) and dopamine (DA), and sacrificed at intervals from 40 min to 24 h post-injection (p.i.). In i.c. injected animals, tritium label is demonstrable as early as 40 min p.i. in neurons of all known NA and DA cell groups. In NA neurons, it is taken up into cell body, dendrites, preterminal and terminal axons. The intensity of neuronal labeling is highest within the first 4 h p.i. and decreases in most neurons with longer postinjection intervals. A significant proportion of both NA and DA neurons degenerate beginning 6 h p.i., the majority show morphological signs of the axon reaction 24 h p.i. Uptake of [3H]6-OHDA into serotonergic and non-catecholaminergic neurons is not demonstrable. [3H]6-OHDA is accumulated by the following extraneuronal cells of the CNS: ependymal cells, epithelial cells of the choroid plexus, subependymal macrophages, smooth muscle cells in the wall of large intraparenchymal blood vessels, meningeal cells and glial cells. The time course of accumulation and disappearance of the label varies among these extraneuronal elements. The meningeal cells show the highest labeling intensity and degenerate within 24 h p.i. After pretreatment of the animals with nomifensine, the uptake of [3H]6-OHDA into NA and DA neurons is totally blocked; by contrast uptake of the labeled drug into extraneuronal cells is not prevented. These findings show that [3H]6-OHDA is not only accumulated by neurons possessing the high-affinity uptake for NA or DA, but by numerous other, extraneuronal cells which also participate in the metabolism of catecholamines.

Animals↗
PubMed1983

6-OHDA-induced ectopia of external granule cells in the subarachnoid space covering the cerebellum. Genesis and topography.

The present report describes the genesis, development and topographical distribution of ectopic cells of the external granular layer in the subarachnoid space covering the rat cerebellum. Following one intracisternal injection to newborn rats of 100 micrograms 6-hydroxydopamine (6-OHDA), the meningeal cells degenerate and are removed by phagocytosis within 24 h post injection (p.i.), leaving the cerebellar cortex without a pia-arachnoid cover. Defects appear in the basal lamina investing the cerebellar cortex 3 to 5 days p.i., and both external granule cells and 'sprouts' from Bergmann-glia endfeet grow into the subarachnoid space. The latter form large, flat glial lamellae and cover extensive areas of the denuded cerebellar surface, although they do not form a glial scar over the exposed neuropil of the cerebellar cortex. The numbers of ectopic external granule cells increase within the subarachnoid space both by proliferation and a continuous efflux of cells from the cerebellar cortex. They migrate, aggregate, and ultimately develop into granule, stellate and basket cells, the morphology of which is indistinguishable from their counterparts in situ; they make specific afferent and efferent connections, both among themselves and with the underlying cerebellar cortex and brainstem. The distribution of ectopic external granule cells and their derivatives is restricted to the anterior vermal fissures and the vermal-hemispheric junctions. The present results indicate that external granule cells and their derivatives are capable of both differentiating normally and surviving in the subarachnoid space if they become associated with glial cells and establish synaptic connections.

Animals↗
PubMed1982

Locus coeruleus - cerebellum: interaction during development.

The presentation describes a combined morphological and biochemical analysis of the developmental interaction between the locus coeruleus (LC) and the cerebellum of rats, which receives an afferent innervation from the LC. The LC neurons are among the first CNS neurons to arise during ontogeny. They establish axonal connections to their target areas while migrating into their nuclear area, where they collect around E17. Their perikaryal development proceeds through the well-known stages of neuronal differentiation, Nissl body formation as a sign of synaptic connectivity appearing for the first time on E18. However, changes in the LC-perikarya are taking place in early postnatal stages. Perikaryal volume increases to reach a transitory maximum of 150% of the adult value on P15. Ultrastructurally, a dissolution of Nissl bodies and an increase in the number of polyribosomes are seen during this developmental period, reminiscent of perikaryal changes during the axon reaction. Later, the organization of ribonucleoproteins into Nissl bodies is re-established. NA axons are demonstrable in the cerebellar anlage for the first time on E17. They increase rapidly in number and organization during cerebellar development as shown by catecholamines histofluorescence. Quantitative measurements of cerebellar high-affinity uptake for NA show that a peak of NA innervation is reached on P10, which amounts to about 250% of the adult value. This hyper-innervation is transitory and declines to adult values on P20. The period of cerebellar NA hyperinnervation corresponds to the perikaryal changes in volume and ultrastructure of LC neurons. The phenomenon of transitory hyperinnervation of a target area is discussed with respect to the establishment of axonal connections during normal development and in regeneration.

Animals↗
PubMed1981

Experimental studies on cerebellar foliation. I. A qualitative morphological analysis of cerebellar fissuration defects after neonatal treatment with 6-OHDA in the rat.

The present report describes the natural history of defective cerebellar fissuration in the rat after neonatal treatment with 6-hydroxydopamine (6-OHDA). Within 24 hours after an intracisternal (IC) injection of 100 micrograms 6-OHDA cerebellar pial fibroblasts degenerated almost completely and were phagocytosed b macrophages within 2-5 days postinjection (dpi) leaving the cerebellar surface denuded of pia. Bergmann glia end feet at first exhibited morphological signs of gliosis and later formed new sprouts that penetrated the basal lamina and grew into the subarachnoid space covering regenerating pial fibroblasts and also invading ectopic colonies of external granular layer (EGL) cells. Breaches in the basal lamina appeared after the pial fibroblast had been destroyed and were confined to areas where Bergmann glia end feet were absent and where EGL cells were opposed to the basal lamina. EGL cells escaped through these fractures into the subarachnoid space in the fissures, where they proliferated to form large colonies of granule and stellate cells. In those fissures in which EGL ectopia featured, opposing folia fused and fissures were lost. These findings suggest that pial fibroblasts and the basal lamina have an important role in maintaining lobular partition during development of the cerebellum, in establishing cerebellar fissures, and in consolidating Bergmann glia-EGL cell relationships as a prerequisite for orderly migration of EGL cells.

Animals↗
PubMed1981

Transitory subependymal cysts in the developing rat rhombencephalon.

A bilaterally symmetrical cystic cavity is situated in the subependymal neuropil of the rostral rhombencephalon of the rat during the perinatal period of ontogeny. These cysts are formed by the confluence of enlarged extracellular spaces in this region between E18 and E20. The cysts are present for about 2 weeks but disappear on about P15 without trace. They have a maximal volume of about 0.004 to 0.006 mm3 on P2, with a rostrocaudal extension of about 200 microm. Their shape is characterized by a medial convexity and a lateral concavity, and they have their maximal circumference at about the middle of the rostrocaudal axis. The caudal portion is juxtaposed to the subependyma, while the rostral part lies in the neuropil of the presumptive griseum centrale pontis. In the lumen and the wall of the cysts are found numerous macrophages, glioblasts and some degenerating axons and dendrites. The significance of these cysts in the context of morphogenesis and the origin of the numerous macrophages within them are both unresolved.

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