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K Fredriksson

Publications and source records attributed to K Fredriksson.

34 records · Page 2Linked to original sources
PubMed1988

Cyst formation and glial response in the brain lesions of stroke-prone spontaneously hypertensive rats.

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 constituents 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 oedema 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 cyto-plasmic 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 of oedema, 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.

Animals↗
PubMed1988

Nerve cell injury in the brain of stroke-prone spontaneously hypertensive rats.

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 well 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 anoxia-ischemia 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.

Animals↗
PubMed1988

Cerebral microangiopathy in stroke-prone spontaneously hypertensive rats. An immunohistochemical and ultrastructural study.

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.

Animals↗
PubMed1988

Carbonates and sulfates in CI chondrites: formation by aqueous activity on the parent body.

Compositions and morphologies of dolomites, breunnerites, Ca-carbonates, Ca-sulfates and Mg, Ni, Na-sulfates, and their petrologic interrelations, in four CI chondrites are consistent with their having been formed by aqueous activity on the CI parent body. Radiochronometric data indicate that this activity took place very early in Solar-System history. No evidence for original ("primitive") condensates seems to be present. However, alteration apparently took place without change in bulk meteorite composition.

Calcium Carbonate↗
PubMed1987

Blood-brain barrier leakage and brain edema in stroke-prone spontaneously hypertensive rats. Effect of chronic sympathectomy and low protein/high salt diet.

Brain edema associated with severe chronic hypertension was studied in stroke-prone spontaneously 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 of 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 less than 0.05) and the incidence of BBB opening was 72% compared to 25% in controls (P less than 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 less than 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.

Animals↗
PubMed1986

The spread of brain oedema in hypertensive brain injury.

Severe hypertension in humans may lead to fibrinoid necroses of cerebral blood vessels with small hemorrhages and cystic necroses. Similar lesions have also been reported in the experimental model of stroke-prone spontaneously hypertensive rats (SHRSP). We examined the genesis and spreading pattern of the brain oedema in SHRSP. The extravasation of plasma proteins was visualized with the Evans-Blue or the immunoperoxidase method. Most commonly the leakage occurred in the grey matter of the cerebral cortex or basal ganglia. The spreading pattern followed that of vasogenic brain oedema with a local spread in the grey matter and an extensive one in the white matter. In addition, we detected a novel pathway upwards along the perivascular spaces of the penetrating vessels as well as laterally in the subpial zone. This route is likely to serve also as a drainage channel for the oedema into the cerebrospinal fluid in the subarachnoidal space. Transfer of the extravasated proteins from the white matter to the ventricles was also observed, confirming that this previously described pathway for the resolution of oedema fluid exists in the SHRSP model of vasogenic brain oedema.

Animals↗
PubMed1985

Cerebrovascular lesions in stroke-prone spontaneously hypertensive rats.

The cerebrovascular lesions of severe chronic hypertension were studied by light microscopy in perfusion-fixed, subserially sectioned brains from stroke-prone spontaneously hypertensive 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.

Animals↗
PubMed1985

Internal carotid and vertebral arteries of spontaneously hypertensive and normotensive rats. A morphometric study on extracranial, intraosseous and intracranial arterial segments.

Arteries from spontaneously hypertensive rats (SHR) and Wistar Kyoto controls (WKY) were investigated. Specified cross-sections were collected from the extra- and intracranial parts of the internal carotid arteries, from the carotid segment situated in the skull bone and from intra- and extracranial segments of the vertebral arteries. The internal radius, media thickness and ratio between media thickness and internal radius (m/r ratio) were calculated for a standardized condition implying a smooth and circular internal elastic membrane. The m/r ratio was significantly increased in all arterial segments of 7-month-old SHR compared to WKY. This was caused mainly by decrease of radius in the vertebral arteries and in the intracranial carotid segment. In the extracranial and intraosseous carotid segments the increase of m/r ratio in SHR was mainly due to an increase of media. Whereas the radius was the same in the intra-osseous and intracranial carotid segments of WKY, the m/r ratio was greater intracranially. The results suggest that the physical properties of supporting tissues may influence the normal arterial development and modify the influence of an increased arterial pressure on the vessel wall.

Age Factors↗
PubMed1985

Cerebral energy metabolism during bicuculline-induced status epilepticus in spontaneously hypertensive rats.

The cerebral blood flow is lower in spontaneously hypertensive rats than in normotensive anaesthetized and mechanically ventilated rats during bicuculline-induced seizures, presumably due to the increase in vascular resistance in the hypertensive rats. This study investigates whether the hypertensive rats develop more severe derangement of the cerebral energy metabolites than normotensive rats because of the reduced cerebral blood flow. After 20 min of continuous seizure activity both normotensive and hypertensive rats had significantly decreased levels of phosphocreatine, ATP and glycogen as well as increased lactate and lactate/pyruvate ratio within the parietal cortex compared to controls. The metabolic disturbances were somewhat less pronounced in the hypertensive rats than in the normotensive rats. Thus, ADP was significantly increased in normotensive rats only and the lactate/pyruvate ratio was higher in the normotensive rats. We conclude that spontaneously hypertensive rats are not more prone than normotensive rats to derangement of cerebral energy metabolites during short term bicuculline-induced seizures and that insufficient blood flow is not the primary cause of the metabolic alterations.

Adenosine Diphosphate↗
PubMed1985

Cerebral arteries in hypertension: structural and hemodynamic aspects.

Chronic hypertension is associated with structural alterations in the cerebrovascular bed, with increased vessel wall thickness and media/lumen ratio over a large range of arterial sizes. In the relaxed cortical surface arteries of spontaneously hypertensive rats and in some segments of the basal arteries, the enlarged media encroaches on the lumen. The altered vessel geometry increases the steepness of the resistance curve and enables the blood vessels to withstand higher intraluminal pressure. On the other hand, the risk for ischemic complications is increased because of an elevated minimal resistance. Pathological, degenerative changes occur when the compensatory mechanisms are insufficient to protect the microvessels from the pressure increases. Small intraparenchymatous cerebral arteries develop hyaline degeneration, fibrinoid necrosis, and microaneurysms with the appearance of hemorrhages and lacunae. Hypertension predisposes for atherosclerosis in the cervicocranial and intracranial basal arteries, increasing the risk for large hemispheric infarcts and transitory ischemic attacks. Stenosis/occlusion of the arteries and embolization from an atheromatous plaque might have a larger impact on the hypertensive than the normotensive brain because of less efficient collateral circulation related to the altered vessel geometry.

Animals↗
PubMed1985

Laser-induced fluorescence from sound and carious tooth substance: spectroscopic studies.

Fluorescence spectra of dentine and enamel illuminated with laser light of wavelengths of 337, 488, 515 and 633 nm respectively were recorded. The fluorescence obtained by illumination with UV laser light at 337 nm had a peak at about 400 nm in dentine as well as enamel. Compared to intact enamel the fluorescence from enamel with initial carious lesions was of lower intensity and had a slight red shift. No fluorescence within the visible range was obtained by illumination with a low power He-Ne laser at 633 nm. Illumination at 488 nm produced fluorescence with a peak at about 540 nm in dentine as well as enamel. The difference in the intensity of fluorescence between sound and carious enamel was generally greater at this wavelength than at any of the others tried, and the red shift from the carious enamel was also more pronounced. Illumination at 515 nm produced fluorescence of similar wavelengths but with much less difference between intact and carious enamel. It was concluded that illumination at 488 nm was the most suitable wavelength of those investigated for the detection of initial carious lesions by the fluorescence technique.

Dental Caries↗
PubMed1984

Regional cerebral blood flow in conscious stroke-prone spontaneously hypertensive rats.

Regional cerebral blood flow (rCBF) was measured autoradiographically with [14C]iodoantipyrine as a diffusible tracer in two strains of conscious normotensive rats (Wistar Kyoto and local Wistar) and in two groups of spontaneously hypertensive stroke-prone rats (SHRSP) with a mean arterial pressure (MAP) below or above 200 mm Hg. In spite of the large differences in arterial pressure, rCBF did not differ significantly between the hypertensive and the normotensive groups in any of the 14 specified brain structures measured. However, rCBF increased asymmetrically within part of the caudate-putamen in two of nine SHRSP with a MAP above 200 mm Hg, indicating a regional drop in the elevated cerebrovascular resistance.

Animals↗
PubMed1984

The hemodynamic effect of bilateral carotid artery ligation and the morphometry of the main communicating circuit in normotensive and spontaneously hypertensive rats.

After reducing the number of patent conduit arteries to the brain by bilateral ligation of the carotid artery, the percentage decrease in blood pressure from the aorta to the internal carotid artery distal to the ligation was larger in spontaneously hypertensive rats than in normotensive rats. The pressure drop corresponded to the degree of hypertension as well as to morphometrically determined structural arterial alteration in the main communicating circuit, i.e. larger media to internal radius ratio and smaller internal radius in the posterior communicating arteries, the proximal part of the posterior cerebral arteries, the basilar artery and the vertebral arteries. The discrepancy between the sum of the luminal cross sectional areas of the communicating circuit and the luminal areas of the ligated conduit arteries was larger in the hypertensive than in the normotensive rats. It is to be expected that occlusion of conduit arteries to the brain will have a larger impact on the cerebral arterial perfusion pressure head in the presence of such hypertensive structural alterations known to increase flow resistance.

Animals↗
PubMedDate not supplied

The morphometry of consecutive segments in cerebral arteries of normotensive and spontaneously hypertensive rats.

The media cross-sectional area, the media thickness, the internal radius and the ratio between media thickness and internal radius were determined in consecutive sections of extraparenchymal cerebral arteries of 7- and 12-month-old normotensive and spontaneously hypertensive rats. The study included intracranial pial and basal arteries as well as extracranial cervical arteries. In the chronically hypertensive rats the media to radius ratio was consistently higher than in normotensive rats over the entire calibre spectrum investigated (radius 5-400 micron). The increase of the ratio in the extracranial arteries of the hypertensive rats was exclusively due to a thicker media. In the basal intracranial arteries the increase of ratio was due to a thicker media and/or a smaller internal radius in 7- and 12-month-old rats with moderate hypertension (mean arterial pressure, MAP 171 +/- 8 and 177 +/- 7 mm Hg respectively). In 7-month-old rats with severe hypertension (MAP 204 +/- 11 mm Hg) the increase of ratio was mainly due to a smaller internal radius. The observed structural alterations are likely to be of hemodynamic importance.

Aging↗
PubMedDate not supplied

Cerebral platelet thromboembolism and thromboxane synthetase inhibition.

Platelet aggregating sodium arachidonate was slowly infused into the internal carotid artery (1 mg, 100 microliters, 1 microliter/s) of nitrous oxide anesthetized rats. The electroencephalographic activity recorded by a Cerebral Function Monitor from the injected hemisphere was reduced within minutes. The somatosensory evoked responses to contralateral electrical stimulation of the whisker area were eliminated on the same side in most cases when measured five and fifteen minutes after the infusion. The brain was frozen in situ with liquid nitrogen after fifteen minutes. Regional tissue analysis showed ipsilateral derangement of the cerebral energy state and increased lactate levels. Pretreatment with the platelet antiaggregating thromboxane synthetase inhibitor OKY-1581 (Sodium-3-4-(3-pyridylmethyl)phenyl-2-methyl-acrylate), 30 mg/kg i.v., fifteen minutes before the sodium arachidonate infusion prevented cerebral energy failure and elimination of the sensory evoked responses.

Acrylates↗