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

Acute transient hypertension by norepinephrine was loaded to stroke-resistant (SHRSR), stroke-prone (SHRSP), and normotensive Wistar Kyoto (WK) rats. (SHRSP were most sensitive to norepinephrine in young pre-hypertensive group.) Its effects on cerebral small vessels were studied using Evans Blue to detect the increase of vascular permeability. Severe macroscopic dye-leakages were observed in the areas of "recurrent branching" and "boundary zone", especially among young SHRSP, while SHRSR seemed to be least prone to dye-leakage both in young and adult groups. Among the adults, there was little difference between SHRSP and WK, probably because of the adaptive structural changes of arterial walls in SHRSP caused by long-standing hypertension.
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PMID:Effect of acute arterial hypertension in stroke-prone and stroke-resistant SHR. 73 99

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.
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PMID:Cerebral microangiopathy in stroke-prone spontaneously hypertensive rats. An immunohistochemical and ultrastructural study. 334 82

1. A study was made of the changes taking place in O(2) consumption, cardiac function and the volume and composition of the body fluids of sheep while they consumed a meal of hay.2. During eating P(a, CO2) and P(v, CO2) both increased, pH decreased and free plasma [HCO(3) (-)] increased. Venous haematocrit increased sharply at the beginning of the meal, and declined slowly after feed was removed.3. Arterial P(O2) did not change significantly during eating. However P(v, O2) fell slightly but significantly. The O(2) saturation of venous blood fell due to the decline in pH. Estimated CO(2) in arterial blood increased as a consequence of increased haemoglobin content. The net effect was to increase arteriovenous difference in O(2) content from 4.4 ml./100 ml. before eating to 6.0 ml./100 ml. at the end of the meal.4. O(2) consumption increased about 60% during eating and fell rapidly thereafter. Heart rate followed a similar pattern. Cardiac output however increased only about 17%, from 6 to 7 l./min. Consequently stroke volume declined throughout the meal from 76 to 52 ml./beat.5. Plasma volume, estimated from measurements of T-1824, declined sharply by about 300 ml. at the beginning of the meal and recovered slowly after feed was removed. Blood volume declined less because of a rise in circulating erythrocytes.6. Extracellular fluid volume was estimated from measurements of thiocyanate and thiosulphate spaces. Thiocyanate space measurements were abandoned after thiocyanate was found to be concentrated in saliva. Considerable random variation occurred in measurements of changes in extracellular fluid from thiosulphate disappearance but the results did reveal a significant fall of 1000-1500 ml. in extracellular fluid volume during eating.7. The significance of these interrelated changes is discussed in relation to the maintenance of homoeostasis during eating in the sheep.
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PMID:Changes during eating in oxygen consumption, cardiac function and body fluids of sheep. 502 Sep 86

Studied was an effect of pentoxyfilline on systemic and cerebral haemodynamics in 33 patients with discirculatory encephalopathy in the presence of atherosclerotic lesion of the precerebral arteries, with the aid of dye-dilution methods using Evans blue (T-1824) and ultrasonic dopplerography. Pentoxyfilline was found to be associated with significant reduction of the circulating blood volume at the expense of its globular fraction, diminution of the cardiac and stroke work indices; the drug has only minor effects on the peripheral vascular resistance and linear velocity of bloodflow in the precerebral arteries; it makes for an increased number of cases of eukinetic type of blood circulation and causes regression of subjective neurologic symptomatology. On account of its antihypertensive and cardiodepressive effect the drug is contraindicated in patients with low AP and hypokinetic type of systemic haemodynamics. If intracerebral steal syndrome is detected, the institution of the pentoxyfilline therapy cannot be recommended.
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PMID:[The effect of pentoxifylline on the systemic and cerebral hemodynamics in patients with circulatory encephalopathy and an atherosclerotic lesion of the precerebral arteries]. 783 83

Focal ischaemia in the rat cerebral cortex was produced by means of a photochemically induced thrombosis of cerebral arteries. This was achieved by intravenous infusion of the photosensitive dye Rose Bengal and illumination of the skull with focused green light. Initial experiments justified the use of tetrazolium staining as an index of infarct damage. Using this technique it was demonstrated that chlormethiazole (200 mg/kg, i.p.) given 5 min post ischaemia markedly reduced the area of infarcted cortical tissue. A second experiment replicated this observation and showed that, in contrast, nimodipine (0.5 mg/kg, i.p.) given 5 min post infarct was without effect on infarct size. The pattern of Evans Blue extravasation indicated that the infarct developed over a 24-h period with the major damage occurring in the first 4.5 h. The spread of the infarct beyond the initial core of damage was decreased by an estimated value of almost 50% by injection of chlormethiazole (200 mg/kg, i.p.) 5 min after the light exposure. These data indicate that chlormethiazole is an effective drug in protecting against the effects of focal ischaemia in the rat and, taken with earlier observations that chlormethiazole protects against the effects of global ischaemia in the gerbil, suggest that the drug may be an effective treatment against the ischaemic cell death that can occur following a stroke or cardiac arrest.
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PMID:The effects of chlormethiazole and nimodipine on cortical infarct area after focal cerebral ischaemia in the rat. 848 58

Brain swelling is a serious complication associated with focal ischemia in stroke and severe head injury. Experimentally, reperfusion following focal cerebral ischemia exacerbates the level of brain swelling. In this study, the permeability of the blood-brain barrier has been investigated as a possible cause of reperfusion-related acute brain swelling. Blood-brain barrier disruption was investigated using Evans Blue dye and [14C]aminoisobutyric acid autoradiography in a rodent model of reversible middle cerebral artery (MCA) occlusion. Acute brain swelling and cerebral blood flow (CBF) during ischemia and reperfusion were analyzed from double-label CBF autoradiograms after application of the potent vasoconstrictor peptide endothelin-1 to the MCA. Ischemia was apparent within ipsilateral MCA territory, 5 min after endothelin-1 application to the exposed artery. Reperfusion, examined at 30 min and 1, 2, and 4 h, was gradual but incomplete within this time frame in the core of middle cerebral artery territory and associated with significant brain swelling. Ipsilateral hemispheric swelling increased over time to a maximum (>5%) at 1-2 h after endothelin-1 but was not associated with a significant increase in the ipsilateral transfer constant for [14C]aminoisobutyric acid over this time frame. These results indicate that endothelin-1 induced focal cerebral ischemia is associated with an acute but reversible hemispheric swelling during the early phase of reperfusion which is not associated with a disruption of the blood-brain barrier.
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PMID:Influence of ischemia and reperfusion on the course of brain tissue swelling and blood-brain barrier permeability in a rodent model of transient focal cerebral ischemia. 934 60

The mechanisms responsible for immediate adjustments in cardiac output at onset of exercise, in the absence of neural drive, are not well defined in heart transplant (HT) recipients. Seven male HT recipients (mean +/- SD 57 +/- 6 years) and 7 age-matched sedentary normal control subjects (mean age 57 +/- 5 years) performed constant load cycle exercise at 40% of peak power output (Watts). Cardiac output and plasma norepinephrine were determined at rest and every 30 seconds during the first 5 minutes of exercise and at minutes 6, 8, and 10. All subjects were admitted to the General Clinical Research Center for determination of plasma volume. After 3 days of equilibration to a controlled and standardized diet, plasma volume was measured using a modified Evans Blue Dye (T-1824) dilution technique. Heart rate at rest was higher in the HT group (105 +/- 12 vs 74 +/- 6 beats/min), but during submaximum exercise, heart rates in the control group increased more rapidly (p < or = 0.05) and to a greater magnitude (54 +/- 7% vs 17 +/- 4% above rest). Stroke volume at rest was lower in HT recipients (45 +/- 4 vs 68 +/- 9 ml) but was significantly augmented immediately after onset of exercise (30 seconds) and the relative increase was greater than controls at peak exercise (61% vs 38% greater than baseline). Cardiac output at rest was within the normal range in both groups (4.58 +/- 0.27 vs 4.94 +/- 0.40 L/min). Relative increases in cardiac output were similar (p > or = 0.05) for the HT (106 +/- 12%) and control groups (97 +/- 10%). Plasma norepinephrine did not become significantly greater than resting values until approximately 4 minutes after onset of exercise in both groups. Blood volume, normalized for body weight, was 12% greater in the HT group. Thus, HT recipients with expanded blood volume (12%) augment stroke volume immediately after the onset of exercise. Plasma norepinephrine levels contribute negligibly to the rapid adjustment in cardiac output. Rather, we speculate that abrupt on-transit increases in stroke volume are due to augmented venous return, secondary to expanded blood volume.
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PMID:Cardiac output responses during exercise in volume-expanded heart transplant recipients. 960 58

The molecular properties of alpha 1-acid glycoprotein are briefly discussed. This molecule has been shown in in vitro experiments to have both a stabilizing effect on vascular permeability and antiinflammatory properties. We were able to demonstrate these two effects in vivo in guinea pigs (skin, Evan's Blue extravasation) and in rats (paw, carrageenan induced inflammation). Further experiments were performed in rats relating to possible therapeutic indications for alpha 1-acid glycoprotein: (1) inhibitory effect on brain edema formation after experimental stroke, (2) therapeutic effect in the puromycin aminonucleoside-induced minimal change nephrosis, (3) improvement of vital parameters in hemorrhagic-hypovolemic shock, (4) increase in survival rate in septic peritonitis, and (5) promising effects in burn-induced remote lung injury. The high content of sialic acid and the high negative charge of alpha 1-acid glycoprotein are believed to be major contributors to its stabilizing effect on vascular permeability. The protein is bound to the glycocalyx of the endothelial cells (and presumably to structures of the glomerular basement membrane), thereby hindering the passage of other polyanionic molecules through the vascular wall. The antiinflammatory/immunomodulatory effect of alpha 1-acid glycoprotein appears mainly due to suppression of polymorphonuclear neutrophils. This action is dependent on the glycan part of the molecule, which is highly variable (microheterogeneity). It is obvious that there are differences between the different glycan forms as far as the antiinflammatory property of the protein is concerned. Together with data in the literature, the results presented here suggest a variety of potential indications for therapeutic use of alpha 1-acid glycoprotein in humans.
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PMID:[Preclinical investigation of alpha 1-acid glycoprotein (orosomucoid)]. 1022 49

Oxidative stress has been associated with the development of blood-brain barrier disruption and cellular injury after ischemia. The cytosolic antioxidant, copper/zinc superoxide dismutase, has been shown to protect against blood-brain barrier disruption and infarction after cerebral ischemia-reperfusion. However, it is not clear whether copper/zinc superoxide dismutase can protect against evolving ischemic lesions after thromboembolic cortical ischemia. In this study, the photothrombotic ischemia model, which is physiologically similar to thromboembolic stroke, was used to develop cortical ischemia. Blood-brain barrier disruption and oxidative cellular damage were investigated in transgenic mice that overexpress copper/zinc superoxide dismutase and in littermate wild-type mice after photothrombotic ischemia, which was induced by both injection of erythrosin B (30 mg/kg) and irradiation using a helium neon laser for 3 min. Free radical production, particularly superoxide, was increased in the lesioned cortex as early as 4 h after ischemia using hydroethidine in situ detection. The transgenic mice showed a prominent decrease in oxidative stress compared with the wild-type mice. Blood-brain barrier disruption, evidenced by quantitation of Evans Blue leakage, occurred 1 h after ischemia and gradually increased up to 24 h. Compared with the wild-type mice, the transgenic mice showed less blood-brain barrier disruption, a decrease in oxidative DNA damage using 8-hydroxyguanosine immunohistochemistry, a subsequent decrease in DNA fragmentation using the in situ nick-end labeling technique, and decreased infarct volume after ischemia. From these results we suggest that superoxide anion radical is an important factor in blood-brain barrier disruption and oxidative cellular injury, and that copper/zinc superoxide dismutase could protect against the evolving infarction after thromboembolic cortical ischemia.
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PMID:The cytosolic antioxidant, copper/zinc superoxide dismutase, attenuates blood-brain barrier disruption and oxidative cellular injury after photothrombotic cortical ischemia in mice. 1153 Feb 38

We monitored alterations in cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability following middle cerebral artery occlusion (MCAo) and intrastriatal transplantation of mouse bone marrow stromal cells (BMSCs) or saline infusion in adult Sprague-Dawley rats. Laser Doppler and Evans Blue assay revealed that BMSC grafts dose-dependently restored CBF and BBB to near normal levels at a much earlier period (Days 4-5 post-MCAo) in transplanted stroke animals compared to stroke animals that received saline infusion (Days 11-14 post-MCAo). Xenografted BMSCs survived in the absence of immunosuppression, and elevated levels of transforming growth factor-beta superfamily of neurotrophic factors were detected in transplanted stroke animals. These data suggest that early restoration of CBF and BBB following transplantation of BMSCs could mediate the reported functional outcomes in stroke animals.
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PMID:Bone marrow grafts restore cerebral blood flow and blood brain barrier in stroke rats. 1512 23


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