Neurofibrillary changes in the cerebral cortex of a patient with subacute sclerosing panencephalitis (SSPE)

Summary Biopsy fragments from the frontal cortex of one patient with SSPE were studied with ultrastructural methods. Special attention was given to the presence of neurofibrillary tangles observed in all cortical layers. These tangles were composed either of filaments with a diameter of 10–12 nm or of paired helical filaments 22–24 nm at their widest and periodically reduced to 10 nm about every 80 nm. These tangles were observed in all cortical layers, while those formed by single filaments were only visualized in layer 3. The simultaneous appearance of both types of tangles in the same patient suggests that they may be chemically related, which is in keeping with recent chemical data concerning the nature of the neurofilament protein subunit.     

Immunoperoxidase staining of simple nuclear bodies in subacute sclerosing panencephalitis (SSPE) by antiserum to measles nucleocapsids

Summary Nuclear bodies have been found with great consistency in brain tissue from patients with subacute sclerosing panencephalitis (SSPE). There has been controversy as to the significance of these structures and their relationship, if any, to the disease. In this study, a non-productive, cell-associated strain of SSPE measles virus grown in tissue culture on Vero cells showed the continued presence of nuclear bodies, frequently in close association with the SSPE measles virus nucleocapsids. Immunoperoxidase (I-P) staining with specific antiserum against measles virus nucleocapsids was done. The resultant positive labeling of the nuclear bodies demonstrates that they contain measles virus antigen and suggests that the nuclear bodies play a role in the development of the measles virus nucleocapsids of SSPE.     

Absence of measles virus receptor (CD46) in lesions of subacute sclerosing panencephalitis brains

In this study we investigated pathological changes of the expression of the measles virus (MV) receptor, CD46, in subacute sclerosing panencephalitis (SSPE) brains. We analyzed CD46 expression in lesions of brain specimens from five SSPE patients in comparison to uninfected regions of the same brains and to normal human brains. The correlation between CD46 and MV infection, in individual cells in SSPE brains, was analyzed by double-staining procedures using monoclonal antibodies (mAbs) and in situ hybridization to detect MV-specific mRNAs. We found that CD46 was expressed at relatively low levels by neurons and astrocytes in normal brains in comparison to neuroblastoma and astrocytoma cell lines. Within heavily infected (MV-positive) brain lesions of all five SSPE cases, CD46 was either not detected or was expressed to a lesser degree by neural cells, irrespective of whether MV antigens were detectable or not. In contrast, normal levels of CD46 were found in SSPE brain tissue distant from the lesion. Using in situ hybridization, mRNAs of both MV nucleocapsid and MV hemagglutinin (MV-H) were detected in all SSPE lesions, while no or only small amounts of MV-H protein were detected. MV-infected neurons were never found to express CD46. Although a strict correlation between levels of the MV-H protein and the absence CD46 could not be seen, these findings suggest that the CD46 expression is reduced by the MV infection in lesions of SSPE brains. Received: 3 March 1997 / Revised, accepted: 30 April 1997     

Coincidental fluctuations of humoral immunity and clinical progression in a patient with subacute sclerosing panencephalitis

Summary Serum and cerebrospinal fluid were obtained from a 6-year-old male with subacute sclerosing panencephalitis (SSPE). Specimens were collected over a 9-month period beginning in the unusually acute phase and ending in a more quiescent phase of the disease. Immune complexes, auto-antibodies and viral antibodies were measured by radio-immunoassays. Fluctuations in these humoral immune parameters coincided with cessation of the acute phase of this disease. The results show that neurological changes in SSPE patients can be reflected in immune responses within both the peripheral circulation and the central nervous system.     

Association of measles virus with neurofibrillary tangles in subacute sclerosing panencephalitis: a combined in situ hybridization and immunocytochemical investigation

Neurofibrillary tangle formation, a cardinal characteristic of Alzheimer's disease, is also a feature of several other neurodegenerative disorders, including subacute sclerosing panencephalitis (SSPE). In the present study the association of measles virus genome with neurofibrillary tangle formation has been studied in five cases of SSPE, using in situ hybridization (measles genome) and immunocytochemistry (tau, ubiquitin and p7A4 amyloid). In two cases with duration of disease less than one year, neurofibrillary tangle formation was not observed. However, in those cases in which the disease was of several years duration, numerous tau– and ubiquitin positive neurofibrillary tangles were demonstrated. In the two cases of longest duration, double–labelling techniques demonstrated the frequent association of neurofibrillary tangle formation with neuronal measles virus genome positivity. Immunocytochemistry for p7A4 amyloid failed to demonstrate amyloid in any of the five cases. These findings support the hypothesis that neurofibrillary tangle formation can occur independently of amyloid formation and that this mechanism may operate in both Alzheimer's disease and in virallyinduced disease.     

Spinal afferents to the ventrobasal thalamic complex in the rat: an anatomical study using wheat-germ agglutinin conjugated to horseradish peroxidase

The anterograde axonal transport of wheat-germ agglutinin conjugated to horseradish peroxidase was used to reassess the spinal afferents to the ventrobasal complex in the rat. Somatotopically-organized labeled fibers and fiber terminals could be observed in the lateral portion of the complex. The distribution of the labeling corresponded to that previously described for afferents originating from the dorsal column nuclei. Terminal fibers were drawn and their morphology analyzed in comparison to that observed for dorsal column nuclei terminals. These results are discussed with reference to the involvement of the ventrobasal complex in the transmission of nociceptive information in the rat.     

Efferent projections of the interpeduncular complex in the rat, with special reference to its subnuclei: a retrograde horseradish peroxidase study

Projections of the subnuclei of the interpeduncular complex were studied by the retrograde horseradish peroxidase technique in the rat. The pars caudalis and pars dorsalis magnocellularis project to the septum, hippocampus and entorhinal cortex; a part of the pars medialis and the pars paramediana, to the dorsal thalamus; all subnuclei, to the midbrain raphe; and the pars lateralis, to the dorsal tegmental nucleus.     

Ascending projections to the mammillary nuclei in the rat: a study using retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase

Cells of origin of ascending afferents to the mammillary nuclei and the afferents' fields of termination within these nuclei were studied by using retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase in the rat. The pars compacta of the superior central nucleus projects bilaterally to the median region of the medial mammillary nucleus. The ventral tegmental nucleus projects ipsilaterally to the medial mammillary nucleus, except for its median region, in a topographic manner such that the rostrodorsolateral part of the ventral tegmental nucleus projects to the medial quadrant of the medial mammillary nucleus; the rostroventromedial part projects to the dorsal quadrant; the caudodorsolateral part projects to the ventral quadrant; and the caudoventromedial part projects to the lateral quadrant. These projection fields extend throughout the longitudinal axis of the medial mammillary nucleus, except for its most caudal region, to which only the dorsolateral part of the ventral tegmental nucleus projects. This nucleus also projects topographically to the ipsilateral dorsal premammillary nucleus; the rostral part of the ventral tegmental nucleus projects to the dorsal part of the dorsal premammillary nucleus, whereas the caudal part projects to the ventral part. The periaqueductal gray around the dorsal tegmental nucleus projects bilaterally to the supramammillary nucleus. The pars alpha of the pontine periaqueductal gray projects bilaterally to the peripheral part of the lateral mammillary nucleus, whereas the pars ventralis of the dorsal tegmental nucleus projects ipsilaterally to the lateral mammillary nucleus. The results show that the tegmentomammillary projections are organized in a gradient fashion, with the rostral to caudal position of cells of origin within the tegmental nuclei of Gudden being reflected by the medial to lateral position of fields of termination within the mammillary nuclei.     

Pretectal and tectal projections to the homologue of the dorsal lateral geniculate nucleus in the pigeon: an anterograde and retrograde tracing study with cholera toxin conjugated to horseradish peroxidase

The possibility of a projection from the pretectal nucleus, lentiformis mesencephali (LM), to the principal optic nuclei (OPT) of the dorsolateral thalamus was investigated using cholera toxin conjugated to horseradish peroxidase (CT-HRP). Injections of CT-HRP into LM produced massive anterograde labeling of the pars lateralis of the nucleus dorsolateralis anterior thalami (DLL), and sparse labeling of the pars magnocellularis (DLAmc). Injections of CT-HRP into OPT in turn produced massive retrograde labeling of both parvocellular and magnocellular divisions of LM. These results relate to possible neural mechanisms underlying optokinetic nystagmus. OPT injections also retrogradely labeled small neurons throughout the rostrocaudal extent of the tectum which were confined to superficial laminae.     

The fibers which leave the Probst's longitudinal bundle seen in the brain of an acallosal mouse: a study with the horseradish peroxidase technique

The congenital absence of the corpus callosum, a brain anomaly frequently noted in humans, has been recently found to occur in some mice of the ddN strain in our laboratory. In the brains of these mice, the Probst's longitudinal bundle is always present on both cerebral hemispheres and gives rise to some aberrant fibers toward the midline. In this research, the neuroanatomical features of these fibers were studied by iontophoretical injections of horseradish peroxidase (HRP) into the neocortex of acallosal mouse brains. The results revealed that the fibers which leave the Probst's longitudinal bundle are, at least, of 3 kinds: namely, the fibers that run out from the anterior portion of the bundle and take a U-turn ipsilaterally without crossing the midline through the septal tissue to go back again into the longitudinal bundle at the level where they have left it; the commissural fibers that leave the bundle from its middle portion and cross through a tiny bridge of tissue associated with the ventral hippocampal commissure to the opposite hemisphere; and the fibers that arise from the posterior portion of the bundle and accumulate as an anomalous fascicle below the cingulum. The observation that no labeled fibers were seen within the anterior commissure in the present HRP materials suggests that the axons from neocortex which are prevented from crossing the midline in mice with congenital absence of the corpus callosum cannot find an alternative pathway via the anterior commissure.     

Morphological identification of brain stem neurones associated with predatory behaviour elicited by lateral hypothalamic electrical stimulation in the cat: a retrograde transport study using horseradish peroxidase subsequent to an electrolytic lesion

The combination of electrical stimulation of the lateral hypothalamus to elicit predatory behaviour, an electrolytic lesion and a subsequent HRP injection was used to identify brain stem neurones whose axons were affected by such hypothalamic stimulation. In contrast, the injection of HRP into such hypothalamic sites, without a prior lesion, resulted in a significant reduction in the number of labelled neurones. This suggests that an important contribution, namely those neurones which give rise to fibres which pass through the stimulated region, is underestimated by the later procedure.     

Migratory pathways and selective aggregation of the lateral reticular neurons in the rat embryo: a horseradish peroxidase in vitro study, with special reference to migration patterns of the precerebellar nuclei

The migration and ultimate domain invasion of postmitotic lateral reticular nucleus (LRN) neurons were followed in embryonic day 15-20 (E15-E20) rat embryos, by using a horseradish peroxidase (HRP) in vitro axonal tracing method. All of the LRN axons elongate and neuronal somata migrate via the subpial or marginal migratory stream (mms), circumnavigating the ventrolateral aspect of the medulla at the glial endfeet level. They reach the ventral midline at E16, bypass it, and begin to settle in their final territory at E17. At E18 the LRN anlage is fully formed, and at E19-E20 its cells have finished their migration and are rapidly differentiating. Comparison of these sequential steps with their counterparts in the development of the inferior olive (ION) and external cuneatus (ECN) brings to light the essential role of the neuroepithelial cells of the interolivary commissure (the "floor plate"). This zone is likely to act as 1) a chemoattractant for the growth cones of the LRN, ION, and ECN, and 2) a decision-making center, which instructs the somata of these neurons to cross the midline or not, ultimately governing the crossed or uncrossed pattern of their projection to their common target, the cerebellum. Finally, the ontogeny of the LRN and ECN provides a most surprising example, even unique in the central nervous system, of long-distance, neurophilic migration that conveys neuronal cell bodies contralaterally to the side on which they proliferate.