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  • 1
    ISSN: 1432-0533
    Keywords: Stroke-prone spontaneously hypertensive rats ; Blood-brain barrier ; Brain edema ; Nerve cell injury ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The brain lesions in stroke-prone spontaneously hypertensive rats (SHRSP) are characterized by multifocal microvascular and spongy-cystic parenchymal alterations particularly in the gray matter. An essential feature of the lesions is the presence of edema with massive extravasation of plasma constituents as evidenced by specific gravity measurements, Evans blue technique and immunohistochemistry. The nerve cell injury occurring in the brain lesions in SHRSP is further characterized by light and electron microscopy in the present study. Two types of neuronal changes were seen within the blood-brain barrier (BBB) leakage sites. A small number of neurons with dark condensed nucleus and cytoplasm were found most often at the periphery of recent lesions. The majority of injured neurons were pale and showed intracellular edema confined to the dendrites and perikarya sparing axons and synapses. Their nuclei were weli preserved with finely dispersed chromatin. The swollen and watery cell processes of neurons and astrocytes gave a spongy appearance to the neuropil. The intracellular edema seemed to result in cytolysis. The results suggest that primary anoxiaischemia is not the major pathogenetic mechanism behind the nerve cell injury in severely hypertensive SHRSP, rather it is the massive BBB leakage and consequent brain edema that causes cytolytic destruction of neurons. Secondary focal ischemia as a consequence of occlusion in microvessels may, however, contribute to the nerve cell destruction.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Stroke-prone spontaneously hypertensive rats ; Blood-brain barrier ; Fibrinoid degeneration ; Brain edema
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cerebrovascular lesions of severe chronic hypertension were studied by light microscopy in perfusion-fixed, subserially sectioned brains from stroke-prone spontaneously hyptertensive rats (SHRSP). The leakage and spread of plasma proteins were visualized by immunohistochemical detection of extravasated fibrinogen and by using an exogenous marker (Evans blue injected i.v.) for blood-brain barrier (BBB) dysfunction. In most SHRSP the hypertension did not lead to major BBB lesions in spite of a mean arterial pressure around 200 mm Hg at 6–9 months of age. Multifocal BBB damage occurred in a minor group of SHRSP, particularly within the cortex and the deep gray matter. A close spatial correlation was found between the leakage-spread of plasma constituents and the neuropathologic alterations. Fibrinoid degeneration of penetrating arterioles was found within the leakage sites. The surrounding gray matter showed petechial hemorrhages and abundant proteinaceous exudates rich in antifibrinogen-positive material. The current leakage of Evans blue and wide spread of fibrinoid substances suggested long-lasting damage to the BBB. Most neurons within the edematous gray matter had well preserved nuclei surrounded by a rim of cytoplasm with ill-defined outline as if vacuolation or lysis of the peripheral cytoplasm had occurred. The sponginess of the tissue progressed in severe cases to formation of necrotic cysts. Condensed acidophilic neurons were seen in the border zone between the edematous and more compact gray matter. The appearance and distribution of the gray matter lesions deviated in many respects from those commonly seen in regional ischemic infarcts. The fibrin thrombi found close to the cysts might be regarded as secondary events. The extensive spread of antifibrinogen-positive material within the white matter seemed to originate mainly from the chronic leakage sites in the gray matter. Increased number of large astrocytes were seen within the leakage sites and along the spreading pathways for the edema constituents. The white matter showed a rarefied texture with widely dispersed nerve fiber tracts, volume expansion, and occasional cyst formation. The results indicate a crucial pathophysiologic role for the egress, spread, and accumulation of vasogenic edema in the development of the cerebrovascular lesions in SHRSP.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0533
    Keywords: Stroke-prone spontaneously hypertensive rats ; Blood-brain barrier ; Brain edema ; Plasma proteins ; Brain specific gravity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Brain edema associated with severe chronic hypertension was studied in stroke-prone spontaneously neously hypertensive rats (SHRSP), 5 to 9 months of age. Blood-brain barrier (BBB) leakage sites and intracerebral spreading pathways for plasma proteins were delineated by an intravenously (i.v.) injected exogenous dye tracer (Evans blue), known to form a complex with albumin in blood, and by immunohistochemical visualization of extravasated endogenous plasma proteins. The tissue content of edema fluid was estimated by measuring the specific gravity of selected brain regions, stained or unstained by the tracer dye, on a bromobenzene-kerosene gradient column. Multifocal BBB leakage sites were macroscopically detected within the cerebral cortex and the deep gray matter after i. v. circulation of Evans blue-albumin for 30 min. After 24 h of i.v. circulation the dye tracer had spread not only locally in the gray matter but also into the adjacent white matter, where it was widely distributed. Immunohistochemically visualized plasma proteins showed similar distribution. Unilateral superior cervical ganglionectomy performed at 4 weeks of age neither increased the incidence of major BBB opening to Evans blue-albumin nor altered the specific gravity of the ipsilateral cerebral hemisphere in grown-up SHRSP, furthermore, the blood pressure remained unchanged. The lack of significant effect on BBB function may possibly be attributed to the extensive reinnervation of the cerebral arteries, verified in the grown-up SHRSP using the Falck-Hillarp fluorescence method for visualization catecholaminergic nerve fibers. In SHRSP raised on a low-protein and high-salt diet the mean arterial blood pressure was 212 mm Hg compared to 195 mm Hg in controls (P〈0.05) and the incidence of BBB opening was 72% compared to 25% in controls (P〈0.05). After 24 h of i.v. circulation of Evans blue-albumin, brain regions stained by the dye tracer showed significantly reduced specific gravity (P〈0.001), while unstained regions had normal values. Thus the brain edema fluid spread, as revealed by specific gravity measurements, corresponded to the intracerebral distribution of extravasated plasma proteins.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 75 (1988), S. 241-252 
    ISSN: 1432-0533
    Keywords: Spontaneously hypertensive rats ; Bloodbrain barrier ; Arterioles ; Fibrinoid degeneration ; Microaneurysm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The morphology of cerebral microvessels was studied immunohistochemically and ultrastructurally in 6- to 9-month-old normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP) with a systolic blood pressure of 138±15 mm Hg, 189±9 mm Hg, and 258±30 mm Hg respectively. Regions with major opening of the blood-brain barrier (BBB) were revealed by an i. v. injection of Evans Blue. Multifocal BBB opening with massive leakage of plasma constituents rich in fibrinogen-fibrin-related antigen occurred in SHRSP with a blood pressure above 210–220 mm Hg. BBB-leakage sites were found in the cerebral cortex and the basal ganglia, most frequently in the arterial border zones. The perivascular tissue spaces were dilated within the BBB-leakage sites, in particular around arterioles. Damaged endothelial and smooth muscle cells were replaced by fibrin-like material, multiple layers of basement membranes and bundles of collagen fibrils surrounded by proliferated fibroblasts. The degenerative-infiltrative-proliferative disease process transformed short segments of single arterioles into severely thickened, tortuous and stenotic vessels. Fibrinoid degeneration, formation of microaneurysms and fibrin-rich vascular occlusions were observed. In contrast, only minor or no vascular alterations were seen in regions with preserved BBB in SHRSP and SHR. A severely increased intraluminal pressure load appears to be of major pathogenetic importance for breakdown of the BBB and initiation of the vascular disease process in SHRSP. However, since only short segments of a limited number of widely separated vessels are severely affected, and the number of affected vessels increase towards arterial end and border zones, additional predisposing and aggravating factors may play significant roles in the development of fibrinoid vascular lesions in arterial hypertension.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0533
    Keywords: Stroke-prone spontaneously hypertensive rats ; Blood-brain barrier ; Brain oedema ; Astrocytes ; Glial fibrillary acidic protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The brain lesions in spontaneously hypertensive stroke-prone rats (SHRSP) are characterised by multifocal microvascular damage, breakdown of the blood-brain barrier, massive extravasation of plasma constitutents and severe brain oedema, with consequent spongy and cystic tissue destruction in the cerebral cortex and basal ganglia as well as loosening of the white matter. In this paper we analyse in greater detail the pathogenetic mechanisms by which the spongy and cystic lesions are formed and the response of astrocytic cells. For this purpose, tracer (Evans blue)-stained brain lesions were examined in 8-month-old SHRSP immunohistochemically and electron microscopically. Sponginess of the neuropil in small lesions and at the periphery of larger lesions was due to swollen neuronal and astrocytic cell processes, i.e.at this stage the oedema was mainly intracellular. Cystic lesions were formed in the grey matter both by expansion of the extracellular space (ECS) containing protein-rich ocdema fluid, and by rupture and subsequent loss of massively swollen cellular elements. In the white matter small slit-formed cysts along the fibre tracts were also formed by the expansion of ECS. In apparently recent lesions astrocytes displayed cytoplasmic oedema but otherwise were still fairly normal. In more chronic lesions increased numbers of enlarged astrocytes with prominent staining for glial fibrillary acidic protein were present. Their distribution corresponded well to the spread ofoedema, i.e. they were prominent around the leaky vessels in the grey matter, in the subpial zone and in the white matter. In the reparative phase the grey matter cysts became lined by astrocytic processes, a new glia limitans. Profuse sheets of glial processes in the neuropil around the cysts reestablished the compactness of the brain parenchyma.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physics Letters A 53 (1975), S. 61-62 
    ISSN: 0375-9601
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physics Letters A 53 (1975), S. 461-463 
    ISSN: 0375-9601
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Earth and Planetary Science Letters 56 (1981), S. 107-126 
    ISSN: 0012-821X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Geosciences , Physics
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Earth and Planetary Science Letters 26 (1975), S. 140-144 
    ISSN: 0012-821X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Geosciences , Physics
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Earth and Planetary Science Letters 78 (1986), S. 80-88 
    ISSN: 0012-821X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Geosciences , Physics
    Type of Medium: Electronic Resource
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