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[Strümpell Lorrain's familial spasmodic paraplegia. An anatomical and clinical review and report on a new case (author's transl)].

The authors describe the anatomical and clinical findings in a case of the pure form of Strümpell Lorrain's familial spasmodic paraplegia. This hereditary condition of the dominant autosomic type has very monomorphic pathognomonic features which are found in all patients affected. The slowly progressive isolated spastic hypertonia appears exclusively in the upright position and the extent of the disease can be ascertained by clinical observation during walking. The myelino-axial degeneration which is strictly limited to the spinal cord has an elective localization in the crossed pyramidal tracts, is less evident in the direct tracts and is mainly predominant in the lumbosacral and low dorsal regions of the cord. The extension of the process beyond the limits of the extrapyramidal tracts confirms the generally accepted unity of spinocerebellar degenerations. In this case the spinocerebellar tracts were less involved than the lumbar spinal ganglia, as well as their distant axial continuation to Goll's tracts only at the cervical level and until the bulber nucleus gracilis.

Brain↗

Cell death in developing human spinal cord.

Cell death in the developing human spinal cord was investigated in 5-12 week human conceptuses using immunohistochemical and TUNEL methods. Expression of pro-apoptotic (Fas-receptor, caspase-3) and anti-apoptotic (bcl-2) markers and marker for internucleosomal fragmentation (TUNEL) were analysed in the cranial and caudal parts of the human spinal cord. In early developmental stages (5-6 weeks) of the cranial spinal cord, bcl-2 positive cells were seen in the ventricular zone and in the roof plate, while in the caudal part they were seen surrounding the central lumen. Subsequently, bcl-2 expression appeared in the basal plates of the grey matter and in the spinal ganglia, and from the seventh week on they also appeared in the intermediate horn of the grey matter. In the fetal period, bcl-2 expression appeared in the dorsal horns of the grey matter (9 weeks) but ceased in the ventricular zone (12 weeks) . In the trunk region, TUNEL-positive cells were found in ventricular and mantle zones along the whole length of the spinal cord. Caspase-3 positive cells and Fas-receptor positive cells appeared only in the grey matter of the cranial segments (head and trunk) of the spinal cord, but they were missing in the caudal parts. Caspase-3 dependant pathway, probably activated by Fas-receptor, seems to operate only in the cranial part of the human spinal cord. In the caudal (sacrococcygeal and tail) parts, cells seem to die by caspase-3 independent pathway. The interplay of pro-apoptotic and anti-apoptotic factors may be associated with cranial spinal cord morphogenesis, adjustment of cells number and selective survival of neurons, while in the caudal regions these factors cause massive cell death associated with regression of the caudal spinal cord.

Apoptosis↗

Studies of hyperalgesia induced by Trypanosoma brucei brucei infection in rats.

Sprague-Dawley rats were infected by intraperitoneal injections of a strain of Trypanosoma brucei brucei. This parasite spreads early to areas in the nervous system which lack a so-called blood-brain or blood-nerve barrier including spinal ganglia. Signs of sensory disturbance in the form of hyperalgesia were observed already seven days post infection, using a hot plate analgesimeter. The sensory disturbances progressed and the rats started to lose weight about 3 weeks post infection, and died about one week later. Immunohistochemistry showed no reduction in density of calcitonin gene-related peptide or substance P immunoreactive fibres in the skin or spinal cord. It is suggested that the sensory disturbances are mediated via release of kinin or interleukin-1 which are known as potent hyperalgesic agents. The hot plate analgesimeter is a simple and reliable method and may be useful in experimental trypanosomiasis to test drugs developed to combat this disease.

Analysis of Variance↗

Experimental cerebrospinal elaphostrongylosis (Elaphostrongylus rangiferi) in goats: II. Pathological findings.

Pathological findings in 17 goat kids inoculated with 100-1,000 infective larvae of Elaphostrongylus rangiferi and autopsied 21-154 days post inoculation (p.i.) are reported. The lungs, heart, diaphragm, liver and kidneys contained small foci of necrosis or fibroblastic scarring and interstitial infiltrates of inflammatory cells. The lungs also contained many parasitic granulomas. Infarcts were observed in the myocardium and kidneys. Accumulations of inflammatory cells and granulomas were seen in the peri- and epineurium of the spinal nerve roots, connective tissue of the spinal ganglia, dura and epidural tissue of the cord, choroid plexus of the brain and leptomeninges of the entire central nervous system (CNS). Within nerve fascicles there were endoneural cell infiltrates, axon and myelin sheath degenerations and granulomas. The CNS parenchyma contained foci of traumatic encephalomyelomalacia, microgliosis, secondary axon degeneration, perivascular cuffs and granulomas. Sections of intact nematodes were found in the subarachnoid spaces, brain ventricles, central canal of the spinal cord and CNS parenchyma. Pathological findings from individual animals are compared to the clinical signs described in a separate paper. The development, migration and pathogenesis of E. rangiferi in goats are discussed.

Animals↗

Cloning and expression of three zebrafish roundabout homologs suggest roles in axon guidance and cell migration.

We report the cloning and expression patterns of three novel zebrafish Roundabout homologs. The Roundabout (robo) gene encodes a transmembrane receptor that is essential for axon guidance in Drosophila and Robo family members have been implicated in cell migration. Analysis of extracellular domains and conserved cytoplasmic motifs shows that zebrafish Robo1 and Robo2 are orthologs of mammalian Robo1 and Robo2, respectively, while zebrafish Robo3 is likely to be an ortholog of mouse Rig-1. The three zebrafish robos are expressed in distinct but overlapping patterns during embryogenesis. They are highly expressed in the developing nervous system, including the olfactory system, visual system, hindbrain, cranial ganglia, spinal cord, and posterior lateral line primordium. They are also expressed in several nonneuronal tissues, including somites and fin buds. The timing and patterns of expression suggest roles for zebrafish robos in axon guidance and cell migration. Wiley-Liss, Inc.

Amino Acid Sequence↗

[Computed x-ray tomographic evaluation of cervico-brachial neuralgia with intravenous injection of contrast media].

Investigation of the cervical epidural space by a CT scan is facilitated by its filling following intravenous injection of a contrast medium. The spinal ganglia and nerve root sheaths are visualized as negative images in the intervertebral foramen. A herniated disc is seen as a focal protrusion of the anterior epidural space presenting a clearer center (60 to 80 HU) than at the periphery (100 to 120 HU). Disco- osteophytic protrusion is seen as an arthritic hypertrophy of the uncus and a more widespread overlapping of the disc, often with a posterior body osteophytosis. The spinal cord and subarachnoid space are also visualized more clearly than when injections are not given. This technique is proposed as the initial examination after standard films, for preoperative investigation of a resistant cervicobrachial neuralgia .

Adolescent↗

Normal segmentation and size of the primary sympathetic ganglia depend upon the alternation of rostrocaudal properties of the somites.

Metameric organization of the dorsal root ganglia (DRG) and ventral roots depends on the alternation of rostrocaudal properties within the somites. In addition, the size of DRG is likely to be regulated by the adjacent mesoderm, because unilateral creation of a paraxial mesoderm with only rostral somitic (RS) halves, leads to the development of non-segmented DRG that are larger and contain more cells than the sum of the contralateral, control DRG. We have now extended our studies of the role of the paraxial mesoderm in the morphogenesis of the peripheral nervous system (PNS) to another metameric PNS component, the sympathetic ganglia (SG). The development of the primary sympathetic chain was studied in chick-quail chimeras with multiple half-somite grafts using quantitative morphometric analysis. In the presence of an exclusively rostral or caudal somitic mesoderm, segmentation of the initially homogeneous primary sympathetic chain into ganglia is prevented. Therefore, the SG, like the DRG and ventral roots, require the normal rostrocaudal alternation of the somitic mesoderm for segmental morphogenesis. On embryonic day 4 (E4), there is a 38% average decrease in the volume of the primary sympathetic chain opposite a RS mesoderm, compared with the primary chain on the unoperated side. This is in contrast to the average increase of 27% in the volume of the DRG opposite the grafted mesoderm in the same embryos. Our results, and classical observations, have led us to propose a model in which the mesoderm controls DRG and SG size by modulating the partition of migrating NC precursors between the anlage of these two ganglion types. According to this model, the reduction in SG volume and concomitant increase in DRG volume observed opposite RS grafts, results from the arrest in the DRG anlage of neural crest cells that normally migrate to the SG.

Animals↗

Localization of sulfated glucuronyl glycolipids in human dorsal root and sympathetic ganglia.

Sulfated glucuronyl glycolipids (SGGLs) in human dorsal root ganglion (DRG) and sympathetic ganglion (SG) were analyzed biochemically and immunohistochemically. SGGLs were enriched in human DRG (1.02 +/- 0.23 micrograms/mg protein), whereas much lower concentrations of these glycolipids (0.043 +/- 0.23 micrograms/mg protein) were detected in SG. Myelin within DRG and SG was immunostained by anti-SGGL antiserum, although only a few myelinated fibers were seen in SG. Nerve cell bodies or unmyelinated fibers were not immunostained. Subcellular fractionation study of human DRG demonstrated that these glycolipids were not only enriched in myelin but also in the axolemma-enriched fraction. These data are consistent with the view that SGGLs may be expressed on myelinated fibers in myelin and axolemma, suggesting that these compounds may play an important role in regulating myelinogenesis.

Chromatography, High Pressure Liquid↗

Quantitative relationships between axoplasm and Schwann cell sheath in unmyelinated nerve fibres. An electron microscope study.

The quantitative relationships between the size of the Schwann cell sheath and that of its related axoplasm were studied by electron microscopy in cross sections of bundles of unmyelinated axons (Remak bundles) of the spinal roots of lizard (Lacerta muralis). It was found that (i) the cross sectional area of the Schwann cell sheath is directly proportional to that of its related axoplasm (correlation coefficient 0.84), and (ii) the ratio between the cross sectional area of the Schwann cell sheath and that of its related axoplasm tends to diminish as the cross sectional area of the latter increases. Thus, under normal conditions, in the bundles of unmyelinated axons of the spinal roots of lizard a quantitative balance exists between the nerve tissue and its associated glial tissue. These results agree with those previously obtained in the myelinated fibres of the same region and in the spinal ganglia of the lizard, gecko, cat and rabbit. Some of the mechanisms probably involved in the control of the quantitative balance between nerve tissue and its associated glial tissue in peripheral nerves are listed.

Animals↗

[Demyelination in in vitro culture in multiple sclerosis: facts and controversies].

The myelinotoxicity of sera from multiple sclerosis (MS) patients was determined by the assessment of visible myelin damage in guinea-pig spinal cord-spinal ganglia and in rat cerebella cultivated on collagen-coated coverslips in Leighton tubes. No change was seen in 22 cases. These data show that serum myelinotoxicity is low in MS - as compared with that of Experimental Allergic Encephalomyelitis. It appears a little specific phenomenon, the mechanism of which remains unclear. It can be easily assessed only in very sensitive culture techniques and is best measured by biochemical methods. This does not preclude the pathophysiological significance of the serum myelinotoxicity in MS. Supernatants of cerebro-spinal fluid (CSF) cell cultures in 10 MS patients caused no demyelination. Pooled concentrated supernatants of CSF cell cultures from 13 to 20 MS patients--containing from 7.3 to 11.7 micrograms IgG/ml gave no patent in vitro demyelination in 3 different experiments. The released products of CSF cell cultures in MS are not very toxic for myelin. However these experiments have to be repeated with more sensitive culture techniques, biochemical assay of myelinotoxicity and more concentrated CSF cultures supernatants.

Animals↗

[Ultrastructure of sensory endings in sympathetic ganglia].

Ultrastructure of dendrites and their sensory terminals in the cat pre- and para-vertebral ganglia has been studied electron microscopically. There have been found specific organelles, i.e. endoplasmic reticulum of a peculiar shape, laminated bodies, mitochondrial aggregates, etc., which are concentrated in the varicosities and terminals of many long dendrites, thus distinguishing them from the dendrites of efferent (post-ganglionic) neurons. Short processes of ganglionic neurons show clusters of small granule-containing vesicles. The localization and relationship of these terminals with other ganglionic structures has been studied. They are shown to originate from the dendrites of sensory neurons of spinal ganglia, as well as from peripheral autonomic neurons whose cell bodies are located in the sympathetic ganglia mentioned.

Animals↗

Effects of thallium salts on neuronal mitochondria in organotypic cord-ganglia-muscle combination cultures.

A functionally coupled organotypic complex of cultured dorsal root ganglia, spinal cord peripheral nerve, and muscle has been employed in an experimental approach to the investigation of the neurotoxic effects of thallium. Selected cultures, grown for up to 12 wk in vitro, were exposed to thallous salts for periods ranging up to 4 days. Cytopathic effects were first detected after 2 h of exposure with the appearance of considerably enlarged mitochondria in axons of peripheral nerve fibers. With time, the matrix space of these mitochondria became progressively swollen, transforming the organelle into an axonal vacuole bounded by the original outer mitochondrial membrane. Coalescence of adjacent axonal vacuoles produced massive internal axon compartments, the membranes of which were shown by electron microprobe mass spectrometry to have an affinity for thallium. Other axoplasmic components were displaced within a distended but intact axolemma. The resultant fiber swelling caused myelin retraction from nodes of Ranvier but no degeneration. Impulses could still propagate along the nerve fibers throughout the time course of the experiment. Comparable, but less severe changes were seen in dorsal root ganglion neurons and in central nerve fibers. Other cell types showed no mitochondrial change. It is uncertain how these findings relate to the neurotoxic effects of thallium in vivo, but a sensitivity of the nerve cell and especially its axon to thallous salts is indicated.

Animals↗

Distribution of vagal afferent fibers of the guinea pig heart labeled by anterograde transport of conjugated horseradish peroxidase.

To determine the distribution of vagal afferent fibers in the heart, wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) or choleragenoid conjugated horseradish peroxidase (B-HRP) was injected into nodose ganglia of guinea pigs. Anterogradely labeled fibers and beaded, terminal-like arborizations were observed in the ascending aorta and aortic arch, the pulmonary trunk and arteries, posterior atrial walls, atrioventricular valves, and ventricles. Control experiments with injection of B-HRP into the cervical vagus nerve indicated that labeled fibers observed in the heart originated from sensory neurons in the nodose ganglia. Neither the density nor distribution of labeling differed between WGA-HRP and B-HRP. Injection of tracer into the left or right nodose ganglion shows that these regions of the heart are bilaterally innervated, although labeling in the left or right posterior atrium was denser after injection into the ipsilateral ganglion. Comparison with a previous study on the distribution of sympathetic afferent fibers in the guinea pig heart suggests that the two afferent systems maintain a complementary, but not mutually exclusive, distribution within the ventricles. Whereas afferents with their source in the spinal ganglia are mainly distributed with coronary arteries on the anterior-superior surface of the ventricles, afferent fibers with their source in the nodose ganglia are concentrated within peri-arterial regions of the posterior-inferior ventricular epicardium and the posterior septal ventricular endocardium. These differences in distributions of afferent systems could play a role in post-infarction autonomic dysfunction and in the symptoms that accompany angina pectoris.

Afferent Pathways↗

A simple method for a specific retrograde labelling of dorsal root and sympathetic ganglion cells innervating the knee joint of the cat.

To examine the biochemical characteristics of primary afferents and sympathetic efferents innervating the normal and inflamed knee joint of the cat, the corresponding perikarya have to be labelled retrogradely. In the present study we used an injection of the fluorescent dye Fast Blue through the intact skin and the patellar ligament into the centre of the knee joint cavity and examined the efficiency of this kind of labelling. The segmental distributions of labelled cell profiles in cryostat sections of dorsal root ganglia (DRG) and paravertebral ganglia of the sympathetic trunk agreed with data obtained previously after applying the dye at the transected end of the two main articular nerves. The soma size distribution of labelled DRG cells was identical to previous results indicating that the perikarya labelled in the present study may be a representative proportion of the knee joint innervation. Axotomy of the medial and posterior articular nerves reduced the number of labelled cell profiles of about 85%. Taken together, these data indicate that an injection of Fast Blue into the knee joint cavity of the cat revealed a highly specific and efficient retrograde labelling of the neuronal cell bodies innervating the knee joint.

Amidines↗

Development of neuron-specific enolase immunoreactivity in avian nervous tissue in vivo and in vitro.

Neuron-specific enolase (NSE) is a glycolytic isoenzyme that is primarily located in neurons and neuroendocrine cells. The development of NSE immunoreactivity in th avian nervous system at the level of the hind limb has been examined using immunocytochemical methods. NSE immunoreactivity is first detected in ventral horn motor neurons and dorsal root ganglion neurons at embryonic day 9-10. This is at least 2-3 days after some neurons in both these populations are capable of electrical activity. The glycogen body, a non-neuronal structure, also exhibits NSE (+) staining, but the onset of this immunoreactivity is earlier, at 8 days of embryonic development. NSE immunoreactivity was absent from the cell bodies of paravertebral sympathetic ganglia throughout development, but was present in cellular processes and terminals in the adult ganglia. NSE immunoreactivity also develops in tissue cultures containing cells of neural tube and neural crest origin.

Animals↗

Substance P and primary afferent transmission.

Substance P has a powerful excitant action on spinal motoneurons of the newborn rat, and the action is specifically antagonized by Lioresal, which also readily blocks spinal reflexes involving primary afferent transmission. Substance P is highly concentrated in bovine and feline dorsal roots as well as in the dorsal part of the dorsal horn of cat spinal cord. There is evidence that substance P is synthesized in spinal ganglia, transported through the dorsal roots and stored in the axon terminals of primary afferent neurons. These and other results suggest that the undecapeptide substance P, or one of its shorter C-terminal analogues, functions as an excitatory transmitter of the primary afferent fibers.

Amino Acid Sequence↗

Retrograde changes in transglutaminase activity after peripheral nerve injuries.

It has been previously demonstrated that transglutaminase activity in rat superior cervical ganglion is rapidly and transiently increased minutes after nerve injury. The present series of experiments sought to determine: (1) whether or not similar changes are expressed by other peripheral neuronal systems, and (2) if injury-induced changes in the enzyme activity can be detected along the injured nerve, and if so do they occur in axons or in non-neuronal cells. In the nodose ganglion transglutaminase activity increased (approximately 40%) 48 h after the vagus nerve was crushed 25 mm from the ganglion. In the vagus nerve the activity was transiently increased (approximately 100%) within 1 h, followed by a second increase (approximately 140%) after 3 h. This occurred only in the proximal nerve stump close to the injury site and not in the section of nerve closer to the ganglion. Comparable enzyme activity was found in unoperated vagus nerve and in distal stumps of previously ligated vagus nerves. In dorsal root ganglia no changes were found for up to 24 h after the sciatic nerve was crushed 40 mm from the ganglion. In the facial nucleus a transient increase was observed after the facial nerve was crushed about 14 mm distally with a peak (approximately 300) at 3 days and a decline within 14 days. A second lesion of the facial nerve made 12 days following a conditioning lesion led to a rebound of enzyme activity in the facial nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗