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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 79 (1990), S. 653-662 
    ISSN: 1432-0533
    Keywords: Taxol ; Neuropathy ; Schwann cells ; Endoneurial cells ; Microtubules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present investigation is a continuation of previous studies showing taxol-induced changes up to 4 weeks after a nerve crush. To evaluate the long-term cellular response to taxol, we have extended our morphological analysis of these changes in the taxoltreated nerve crush for up to 40 weeks after a single injection of taxol (PI). The results showed that Schwann cells exhibited a long-lasting and marked response when taxol was injected into the crushed peripheral nerve. During the first 2 months PI, taxolinduced giant axonal bulbs showed the formation of primitive nodes of Ranvier as a result of Schwann cell invaginations. The Schwann cell invaginations developed into nodes of Ranvier after 3–4 months PI together with the recovery of axonal bulbs. Ultrastructurally, cytoplasmic microtubule-related abnormalities were numerous up to 3 months PI and microtubules were seen to enclose degenerative myelin. Taxol-induced abnormalities in Schwann cells did not prevent their ability to produce myelin sheaths, although the accumulation of microtubules between myelin lamellae caused swellings of Schmidt-Lanterman incisures and paranodal myelin loops. Abnormal, extracellular collagen-like 5-nm-thin fibrils were noted closely associated with Schwann cells up to 10 weeks PI. Endoneurial cells, present as long rows without interconnections were noted in areas devoid of axonal sprouts up to 6–8 weeks PI. These cells showed marked cytoplasmic elongations and were covered by thickened basal lamina and contained several microtubule-related cytoplasmic structures, some of which have not been described previously. Taxol, when injected into crushed sciatic nerve induced a long-lasting response upon the Schwann cells with several ultrastructural abnormalities which correlate with changes in myelination and the development of nodes of Ranvier. These findings suggest that normal microtubule turnover is necessary for Schwann cells during nerve fiber regeneration.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 55 (1981), S. 97-103 
    ISSN: 1432-0533
    Keywords: Infantile striatal necrosis ; Computed tomography (CT) ; Morphology ; Excitotoxic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of infantile bilateral striatal necrosis (IBSN) is reported, the first one found in Scandinavia. Extensive clinical and laboratory investigations did not reveal any evidence of a neurometabolic disease. By computed tomography (CT) degeneration of putamen of either side was detected. The neuropathologic findings included extensive bilateral destruction of the striatum and pallidum and degeneration of the substantia nigra and tegmental nuclei. In the damaged regions, accumulations of cells containing sudanophilic lipids were found and Alzheimer type II glial cells, which were also seen in the cortex. On the basis of the clinical picture and the destruction of nerve cells in particular areas of the brain, in the present case and previously published cases of IBSN, the possible role of glutamatc and other excitotoxic transmitters in the pathogenesis of the disease is discussed.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 74 (1987), S. 13-21 
    ISSN: 1432-0533
    Keywords: Collagen ; Schwann cells ; Peripheral nerve ; Connective tissue ; Nerve regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The connective tissue changes during Wallerian degeneration and subsequent regeneration were studied in the distal stump of transected sciatic nerves of Wistar rats. In half of the animals regeneration was prevented by suturing the distal stump to muscle and in the rest spontaneous regeneration was allowed. Intact contralateral nerves served as controls. By 4 weeks after transection the Schwann cell columns became surrounded by a layer of thin collagen fibrils that were, on average, 25–30 nm in diameter. This was only half of the fibril diameter observed elsewhere in the endoneurium or in control nerves. The layer of thin fibrils diminished in thickness when axonal regeneration reached the distal stump, especially as the axons became myelinated. At all stages of the experiment the fibril diameter distribution in the surrounding normal endoneurial stroma was comparable with that observed in control nerves. Segments of Schwann cell basement membrane were observed to be closely associated with collagen fibrils both in freely regenerating, as well as in non-regenerating, nerves. The diameter of these fibrils corresponded to that observed in the zone of thin fibrils surrounding the Schwann cell columns. Such areas were not found in control nerves. The data obtained show that deposition of thin collagen fibrils occurs around the Schwann cell columns as a reaction to transection. Our observations on the regenerating nerves indicate that this connective tissue reaction does not prevent regeneration in the early phases following injury and that its progression is limited concomitantly with axonal regeneration.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 46 (1979), S. 231-234 
    ISSN: 1432-0533
    Keywords: Multiple sclerosis ; Anaplastic astrocytoma ; Measles virus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An ununsual case of concurrent MS and anaplastic astrocytoma is presented. MS was diagnosed in a female patient at the age of 22 years. A left side thalamotomy was performed for relief of severe intention tremor at age 28 and at age 32 she received immunosuppressive therapy for 1 year. At the age of 36 after a severe exacerbation of her symptoms a left side fronto-temporal tumor was diagnosed and a subtotal neurosurgical extirpation was performed. Histopathologically, the tumor was an anaplastic astrocytoma, which was further substantiated by electron microscopy and establishment of a permanent cell line in vitro. The cultured tumor cells were negative for measles virus by immunofluorescence. The relationship between the reactive astrocytes in MS plaques and astrocytic neoplasia is discussed.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0533
    Keywords: Wallerian degeneration ; Schwann cells ; Fibroblasts ; Nerve tissue protein S-100
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Schwann cells and endoneurial fibroblastlike cells were quantitatied for 30 weeks in both nonregenerating and freely regenerating, transected rat sciatic nerve. Immunocytochemical recognition of S-100 protein was used as a marker for Schwann cells and other immunocytochemical and histological methods in the differentiation of S-100 protein-negative endoneurial cells in cross sections of the distal stump 10 mm distal to the site of transection. A marked increase in the total number of cells was observed during the first 4 weeks after the injury in both operative groups. The quantitative relationships between cell populations remained essentially the same as in normal nerves, although the proliferation of the S-100 protein-negative cell population was proportionately slightly stronger when compared to the number of these cells in normal nerves. After the initial proliferation, a gradual decrease occurred in the total number of cells per cross section. This was most marked in the non-regenerating nerves, whereas in the regenerating nerves the decrease in cell number ceased at 16 weeks. The number of Schwann cells was 3.5 times as high as in the control nerves in this phase. The method used in the present study is less laborious than morphometry employing electron microscopy. Furthermore, electron microscopic characteristics of endoneurial cells are not always reliable after nerve trauma, because normal anatomical relationships have become disturbed. This study demonstrates that S-100 protein immunocytochemistry is useful in the study of traumatic lesions of peripheral nerve.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 76 (1988), S. 17-25 
    ISSN: 1432-0533
    Keywords: Taxol ; Neuropathy ; Nerve crush ; Microtubules ; Schwann cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of taxol, an antimitotic drug which stabilizes microtubules and promotes their assembly, was studied with regard to Schwann cells over a 4-week period following a crush injury to rat sciatic nerve. A single intraneural injection of taxol in dimethyl sulfoxide (DMSO) was given immediately after the crush into the site of injury in one sciatic nerve and was compared with the other side which was crushed but injected with DMSO only. Sampled sites were taken proximal and distal to the lesion, as well as from the lesion itself, and studied by light and electron microscopy. The Schwann cell response was most marked during the degenerative phase immediately following the crush. At this time, there was a decrease of all cytoplasmic structures except microtubules and smooth endoplasmic reticulum. At the site of the crush lesion in taxol-treated nerves, Schwann cells possessed accumulations of myelin debris and lipid droplets. Mitotic Schwann cells were also engorged with myelin breakdown products. Multinucleated Schwann cells, believed to be the result of abnormal mitotic activity, were also apparent and were filled with large numbers of cytoplasmic microtubules. The latter were sometimes regularly arranged around phagocytosed or intracytoplasmic debris. Some recovery from the crush injury was noted with time, although the number of Schwann cells was much lower than would have been anticipated in the absence of taxol, in that long stretches of naked axon bundles were common and microtubule-related abnormalities persisted up to 4 weeks. Myelination of regenerating axonal sprouts was delayed and might have been related to axons being swollen due to the build-up of microtubules. However, some myelination was noted sporadically along a few axons in taxol-treated nerves after 4 weeks. The present results suggest that the rapid Schwann cell reaction after nerve crush was impeded by the adverse effect of taxol upon mitosis and cell migration and that Schwann cells play an active role in the degradation of myelin phagocytosis of debris during Wallerian degeneration.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 76 (1988), S. 26-34 
    ISSN: 1432-0533
    Keywords: Taxol ; Neuropathy ; Nerve crush ; Microtubules ; Axons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of taxol, a compound renowned for its ability to promote microtubule assembly, were studied upon axons after its injection into rat sciatic nerve immediately following a local nerve crush injury. The single injection of taxol was delivered into the lesion site and the animals were sampled up to 4 weeks post-injection (PI) for morphological study. At the lesion site, Wallerian degeneration was encountered and this was followed by axonal sprouting by 5 days PI. In contrast to axonal sprouting seen in uninjected controls (crush-only), sprouts in taxol-injected nerves rapidly became swollen due to an increasing number of axoplasmic microtubules. By 2 weeks PI, this led to the formation of giant axonal bulbs from which by 3 weeks PI, a secondary wave of regenerative growth occured consisting of thin, haphazardly twisted axonal twigs largely lacking Schwann cell investment. These were most numerous after 3 and 4 weeks PI. Within the affected axoplasm, microtubules occasionally formed occasional channles around mitochondria. The present results, characterized by the more rapid appearance of taxol-induced giant axonal bulbs in regenerating sprouts than seen after taxol injection of intact nerve, suggest that regenerating PNS axons are exquisitely sensitive to and dramatically affected by taxol. The conclusions support previous observations on a crucial role for microtubules during early axonal growth.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 76 (1988), S. 35-45 
    ISSN: 1432-0533
    Keywords: Endoneurium ; Axotomy ; Wallerian degeneration ; Onion bulb neuropathy ; Renaut bodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Long-term endoneurial changes in the distal stump of transected rat sciatic nerve were examined from 8 to 50 weeks after nerve transection. The morphological alterations were followed both in nerves which were allowed to regenerate and in nerves in which regeneration was prevented by suturing. The nerves prevented from regenerating showed markedly atrophied Schwann cell columns after 20 weeks and a disappearance of some Schwann cell columns after 30 weeks. The surrounding endoneurial fibroblast-like cells gradually lost their delicate cytoplasmic extensions and formed rough fascicles around numerous shrunken Schwann cell columns or around areas from which Schwann cells had apparently disappeared. Inside the fascicles, the Schwann cell loss was replaced by collagen fibrils or occasionally, by a dense accumulation of microfibrils. The loss of endoneurial cytoplasmic processes continued up to 50 weeks, leaving behind patches of thin fibrils around numerous shrunken Schwann cell columns or around collagenous areas where Schwann cells were lost. The endoneurial matrix showed presence of thin 25- to 30-nm collagen fibrils close to shrunken Schwann cell columns up to 50 weeks but in areas with advanced degeneration a shift towards regular 50- to 60-nm collagen fibrils occurred. The degenerated areas resembled those described in Renaut bodies and neurofibromas. Despite suturing of transected nerves to prevent sprouting, occasional regenerating sprouts were noted in the Schwann cell columns. These axons were surrounded in a sheath-like fashion by pre-existing endoneurial cell fascicles covered by a basal lamina. In the reinnervating nerves the endoneurial space gradually lost its compartmentized structures consisting of collagen fibrils and endoneurial fibroblast-like cells. After 20 weeks the endoneurial cells were inconspicuous and the extracelluar matrix consisted mainly of 50- to 60-nm collagen fibrils. During axonal growth and maturation, Schwann cells containing unmyelinated axons surrounded large, myelinated axons in a collar-like fashion. Close to these collars of Schwann cells, thin 25- to 30-nm collagen fibrils were noted in focal areas, even after 50 weeks. Occasionally, numerous clusters of regenerating axonal sprouts were noted in the perineurium. These were surrounded by multiple layers of cells possessing basal lamina. The present results show that after nerve transection the distal stump of the severed nerve shows dynamic changes in the endoneurial space, especially in nerves where reinnervation is prevented. The endoneurial fascicles around occasional axonal sprouts in sutured nerves, representing possibly a delayed type of regeneration, show that axons have a strong ability to grow but on the other hand endoneurial structures are unable to respond normally to axonal growth after advanced degeneration.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0533
    Keywords: Key words Alpha-synuclein ; Cortical Lewy bodies ; Cognitive impairment ; Parkinson’s disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Amygdala, hippocampus and six cortical gyri were examined for the Lewy body (LB) degeneration and Alzheimer’s disease (AD) type changes in 45 patients with Parkinson’s disease (PD). For detection of LBs, the brain areas were stained with an antibody against alpha-synuclein. The extent of neuropathological lesions was investigated in relation to cognitive dysfunction and apolipoprotein E (apoE) ɛ4 allele dosage. At least one cortical LB was found in 95% of cases (43/45). Furthermore, 40% of cases (18/45) had histological findings of definite AD (CERAD class C). Those PD cases with the apoE ɛ4 allele had a significantly greater number of cortical LBs than those without the apoE ɛ4 allele, but this was statistically significant only in precentral, angular and temporal gyri. The LB density correlated better with the number of plaques than with the density of tangles. The number of LBs in several cortical areas correlated significantly with the cognitive impairment. In stepwise linear regression analysis, the number of LBs in the cingulate gyrus and the amount of tangles in the temporal cortex remained statistically significant. When the CERAD class C was excluded, the correlation between cognitive decline and the number of LBs in cortical areas became even more pronounced. A stepwise linear regression analysis in these cases found the number of LBs in the frontal gyrus to be the statistically most significant predictor of cognitive impairment. This study shows, for the first time, that in PD, alpha-synuclein-positive cortical LBs are associated with cognitive impairment independent of AD-type pathology.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 73 (1987), S. 323-329 
    ISSN: 1432-0533
    Keywords: Wallerian degeneration ; Nerve regeneration ; Endoneurium ; Extracellular matrix
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Endoneurial changes in the rat sciatic nerve were studied during Wallerian degeneration and subsequent regeneration. After total axotomy two different experimental models were used. In the first the cut ends of the sciatic nerves were left free to allow reinnervation. In the second model the distal end of the transected nerve was sutured to the adjoining muscle to prevent regeneration. Within 2 weeks after the axomoty, a Wallerian type of degeneration was seen with axonal destruction and phagocytosis of myelin sheaths. After 4 weeks endoneurial fibroblastic cells formed circular structures around the Schwann cell columns, i.e., the bands of Buengner in both groups. These fascicle-like structures became more pronounced in the non-regenerating nerves up to 8 weeks, while during reinnervation the cellular reaction in the endoneurium nearly disappeared within this time. Ultrastructurally, the endoneurial fibroblast-like cells showed marked phagocytotic activity and also fragments of basement membrane on their surface. The appearance of thin (25–30 nm in diameter) collagen fibrils closely related to the basement membrane was noted around the bands of Buengner, as well as the appearance of an amorphous extracellular gap between the newly synthetized thin collagen fibrils and normal endoneurial collagen (50–60 nm). The reversible endoneurial compartmentation seems to be important for maintaining the nerve structure, serving as a support for axonal regeneration in addition to the bands of Buengner.
    Type of Medium: Electronic Resource
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