Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Cyst formation and glial response in the brain lesions of stroke-prone spontaneously hypertensive rats. 318 37

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.
 ...
PMID:Nerve cell injury in the brain of stroke-prone spontaneously hypertensive rats. 321 25

This investigation examined the presence and abundance of vasopressin-gene messenger ribonucleic acid (mRNA) transcripts in hypothalamic tissue from five strains of rats: Long Evans, Wistar-Kyoto, and diabetes insipidus (Brattleboro) rats, stroke-prone spontaneously hypertensive rats, and cross-bred diabetes insipidus x stroke-prone spontaneously hypertensive rats. A single-stranded RNA probe complementary to exon C of the vasopressin gene was utilized for in situ hybridization and identified hypothalamic 'vasopressinergic' neurons in tissue from all five strains of rats. The results obtained by solution and in situ hybridization suggested the cross-bred diabetic-hypertensive rat exhibits a level of vasopressin-gene messenger ribonucleic acid similar to diabetes insipidus rats. This observation is consistent with previous physiological data which suggests cross-bred diabetic-hypertensive rats inherit the mutated vasopressin gene of the Brattleboro rat.
 ...
PMID:Vasopressin gene expression in hypertensive, normotensive, and diabetes insipidus rats. 324 86

The inotropic responses of chronic alcoholic and control rat hearts to phenylephrine, glucagon, ouabain, and dobutamine were studied to determine if the reported beta-adrenergic subsensitivity of alcoholic rat hearts was a specific defect. Male Long-Evans rats were maintained on nutritionally-complete liquid diets for 10 to 12 months; alcoholic rats received 38% of their calories from ethanol. Dry heart weight/body weight ratios indicated an average 15% hypertrophy of the alcoholic rat hearts. The function of isolated working hearts from these animals was studied at a constant heart rate and afterload. Ventricular function curves indicated significantly lower basal function of alcoholic rat hearts, as evident from their lower peak left ventricular relaxation rate, lower isovolumic relaxation rate, and lower peak power compared to controls. The alcoholic rat hearts had significantly lower inotropic (stroke work and peak power) responses to phenylephrine, glucagon, and dobutamine compared to controls, whereas the response of the alcoholics to ouabain was not significantly different from that of controls. Oxygen supply-to-utilization ratios decreased similarly in alcoholics and controls during treatment with the inotropic agents, as a result of increases in myocardial oxygen consumption and effects on coronary flow that were similar in both groups of animals. Thus the differences in inotropic responses observed with the alcoholic rat hearts were not primarily the result of compromised oxygen supply. Rather, the decreased stroke work response of the alcoholic hearts which occurred despite an increase in oxygen consumption suggested that the alcoholic rat hearts did not utilize oxygen as efficiently as did control hearts to perform external work. This was reflected in the significant differences between alcoholics and controls in the response of calculated external work efficiency to phenylephrine, glucagon, and dobutamine. Thus, alcohol-induced cardiac hypertrophy was associated with depressed basal left ventricular contractile function and decreased responsiveness to alpha 1-adrenergic, beta 1-adrenergic, and glucagon stimulation, but the responsiveness to ouabain was not significantly affected. These characteristics are similar to those of hearts hypertrophied by other causes.
 ...
PMID:Alcoholic cardiomyopathy in rats: inotropic responses to phenylephrine, glucagon, ouabain, and dobutamine. 343 59

Peak aortic blood velocity (Vel), peak acceleration (Acc), stroke volume (SV), and left ventricular (LV) ejection fraction (EF) have been used as noninvasive indicators of global LV performance. The purpose of this study was to determine which of these indices of LV performance relates best to the extent of LV ischemic mass at risk. Studies were performed in 24 open-chest anesthetized dogs. Acute ischemia was produced by occlusion of various levels of the left anterior descending and circumflex coronary arteries. LV ischemic mass, measured as a percent of total LV mass, was delineated by injection of Evans blue dye into the nonischemic zone. Acc and Vel were measured with continuous-wave Doppler ultrasound. EF was measured angiographically. All parameters were measured during a control period and within 6 minutes of coronary occlusion. The percent change during ischemia of each parameter relative to control (% delta) was calculated. The correlation coefficient between the percent ischemic mass at risk and % delta Acc was 0.88. It was 0.84 for % delta EF, 0.77 for % delta Vel, and 0.17 for % delta SV. These results indicate that among the various global indices of LV performance that have been used noninvasively, Acc correlates most closely with the extent of LV ischemic mass at risk.
 ...
PMID:Peak aortic blood acceleration reflects the extent of left ventricular ischemic mass at risk. 355 72

Alterations in the blood-brain barrier to proteins, and regional water and electrolyte content were documented in a rat model of photochemically induced small-vessel thrombosis leading to infarction. Horseradish peroxidase (HRP) or Evans blue was given immediately following a 2-min photochemical sensitization period. At 5 min following irradiation, multifocal sites of peroxidase extravasation were noted within the irradiated area. Ultrastructural examination revealed endothelial cells filled with HRP which in some cases extended into the basal lamina and extracellular spaces. At 15 min, protein leakage was more pronounced within the irradiated zone and reaction product was also apparent within the subarachnoid and perivascular spaces of brain regions remote from the site of irradiation. Widespread staining on the surface of the irradiated hemisphere was apparent in rats perfused 8 h following Evans blue infusion. Water content increased significantly by 15 min within the irradiated zone but not in brain regions remote from this site. Although vasogenic edema is an early event in this stroke model, increases in water content are restricted to the irreversibly damaged site. In contrast, protein tracer escaping from microvessels coursing within the irradiated zone was widely distributed. These findings implicate endothelial barrier dysfunction in the genesis of tissue injury in this model. Morphological evidence for the capability of macromolecules to escape from a site of evolving infarction and to migrate to distances remote from the area of primary microvascular damage is also discussed.
 ...
PMID:Photochemically induced cerebral infarction. II. Edema and blood-brain barrier disruption. 357 88

The cardiovascular effects of an acute haemorrhage (2% of the body weight) were studied over a 60 min period in three groups of rats: (a) Brattleboro rats with hereditary hypothalamic diabetes insipidus (b.d.i.) lacking circulating vasopressin, (b) control rats of the parent Long Evans (l.e.) strain, and (c) l.e. rats treated with an antagonist of the vascular action of vasopressin. Prior to the haemorrhage there were no significant differences between the three groups of rats with respect to mean arterial blood pressure, cardiac output, stroke volume or total peripheral resistance. Following the haemorrhage cardiac output and stroke volume were severely reduced in all three groups of rats. Total peripheral resistance was relatively unaffected in antagonist-treated l.e. rats and b.d.i. rats, but rose substantially in response to the loss of blood in the control l.e. group. Both total peripheral resistance and mean arterial blood pressure were markedly greater in the untreated l.e. control rats than in the other two groups of animals during the first 20 min after haemorrhage. The mean heart rate measured in Brattleboro rats was elevated compared with that of control l.e. rats throughout the experiment and, in addition, significantly greater than that of antagonist-treated l.e. rats during the first 40 min after the haemorrhage. Survival rate for the b.d.i. rats following the 2% haemorrhage was lower than that for l.e. control rats and antagonist-treated l.e. rats. The results indicate that the recovery of the blood pressure following an acute arterial haemorrhage is significantly influenced by vasopressin, particularly during the first 20 min, and that the predominant effect of the hormone is to increase the total peripheral resistance. The higher mortality associated with volume depletion in the b.d.i. rats is unlikely to be directly related to the absence of the vascular action of vasopressin, since administration of the vasopressin antagonist to normal l.e. rats does not reduce their survival rate.
 ...
PMID:The cardiovascular effects of vasopressin after haemorrhage in anaesthetized rats. 364 10

In a study involving 33 patients with initial manifestations of inadequate cerebral blood supply and in 22 patients with transient disorders of the cerebral circulation in the presence of atherosclerosis (n = 45) and atherosclerosis with arterial hypertension (n = 8) the authors studied the effect of intravenous administration of cavinton in combination with sulfocamphocain on the clinical manifestations and on the systemic (using the method of Evans' dilution) and cerebral (using Doppler ultrasonography) hemodynamics. It has been demonstrated that both a single intravenous administration of cavinton in conjunction with sulfocamphocain and a course of treatment with these drugs reduce the volume of the circulating blood, lower the stroke and cardiac indices, increase the linear velocity of blood flow along the carotid and vertebral arteries, and decrease neurological symptomatology. The authors discuss the questions related to indications for the administration of cavinton in combination with sulfocamphocain to patients with inadequate cerebral blood supply and transient disorders of the cerebral circulation.
 ...
PMID:[Effect of cavinton and sulfocamphocain on systemic and cerebral hemodynamics in patients with early forms of cerebrovascular diseases]. 367 9

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.
 ...
PMID:Blood-brain barrier leakage and brain edema in stroke-prone spontaneously hypertensive rats. Effect of chronic sympathectomy and low protein/high salt diet. 367 18

The influence of chronic arterial hypertension upon the permeability to albumin of the cerebral capillaries, i.e. the blood-brain barrier, was studied in normotensive Wistar and spontaneously hypertensive Wistar rats with experimental subarachnoid hemorrhage. The blood-brain barrier permeability to albumin was assessed quantitatively by spectrophotometric determination of Evans blue extravasation. Subarachnoid hemorrhage was produced by injecting autologous blood into the cortical subarachnoid space. A significant increase of Evans blue albumin extravasation was found in the spontaneously hypertensive rats with subarachnoid hemorrhage as compared with normotensive animals suffering from subarachnoid hemorrhage. Subarachnoid hemorrhage in this model alone caused a significant Evans blue extravasation, whereas sham-operation did not. These findings emphasize the necessity for effective attempts to reduce the leakage of the capillary system in the early stage of subarachnoid hemorrhage.
Stroke
PMID:Increased vulnerability of the blood-brain barrier to experimental subarachnoid hemorrhage in spontaneously hypertensive rats. 371 50


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>