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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As thrombolytic therapy for treatment of ischemic stroke was propagated, much attention has been paid to reperfusion brain injury. Oxidative stress is one of the most important factors that exacerbate tissue damage by reperfusion. Thus, we investigated the extent of oxidative damage in rat brain after transient middle cerebral artery (MCA) occlusion by immunohistochemical analysis for 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is one of the best markers of oxidative damage. Furthermore, in order to investigate its role in neuronal cell death, we performed terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) study, and compared the results with that of 8-OHdG immunohistochemistry. There was no immunoreactive 8-OHdG in sham-operated brain, but it became present in neurons of MCA territory at 3 h of reperfusion after 90-min ischemia. At 48 h after reperfusion, cerebral tissue of MCA territory was severely destroyed, and many cells in that area revealed TUNEL positivity. Some neurons in MCA territory showed mild immunoreactivity for 8-OHdG at that time, but it was strongest in neurons in the outer area of MCA territory. Those cells did not show TUNEL positivity, suggesting that 8-OHdG production is not necessarily followed by early cell death. Here, it was demonstrated that oxidative DNA damage occurs in more extended area than that where cell death is recognized. Although this damage does not cause early cell death, this might result in more prolonged cell dysfunction and eventual neuronal loss. Anti-oxidant therapy might be required for treatment of stroke in the future.
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PMID:Oxidative damage and breakage of DNA in rat brain after transient MCA occlusion. 1037 62

1. The amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of the total systemic oxidative stress in vivo, in stroke-prone spontaneously hypertensive rats (SHRSP) was not different from that in control normotensive Wistar-Kyoto (WKY) rats at 6 weeks of age, but became higher than control values after the development of severe hypertension at 14-17 weeks of age. 2. The amount of urinary 8-OHdG was not significantly different between SHRSP treated with anti-hypertensive agents and those not treated at 14 weeks of age. 3. Stroke-prone spontaneously hypertensive rats were exposed to DNA damage by oxidative stress at the early stage when they developed severe hypertension, but this increase in DNA damage was not the secondary effect of hypertension.
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PMID:Increased oxidative DNA damage in stroke-prone spontaneously hypertensive rats. 1038 43

Experimental stroke using a focal cerebral ischemia and reperfusion (FCIR) model was induced in male Long-Evans rats by a bilateral occlusion of both common carotid arteries and the right middle cerebral artery for 30-90 min, followed by various periods of reperfusion. Oxidative DNA lesions in the ipsilateral cortex were demonstrated using Escherichia coli formamidopyrimidine DNA N-glycosylase (Fpg protein)-sensitive sites (FPGSS), as labeled in situ using digoxigenin-dUTP and detected using antibodies against digoxigenin. Because Fpg protein removes 8-hydroxy-2'-deoxyguanine (oh8dG) and other lesions in DNA, FPGSS measure oxidative DNA damage. The number of FPGSS-positive cells in the cortex from the sham-operated control group was 3 +/- 3 (mean +/- SD per mm(2)). In animals that received 90 min occlusion and 15 min of reperfusion (FCIR 90/15), FPGSS-positive cells were significantly increased by 200-fold. Oxidative DNA damage was confirmed by using monoclonal antibodies against 8-hydroxy-guanosine (oh8G) and oh8dG. A pretreatment of RNase A (100 microg/ml) to the tissue reduced, but did not abolish, the oh8dG signal. The number of animals with positive FPGSS or oh8dG was significantly (P<0.01) higher in the FCIR group than in the sham-operated control group. We detected few FPGSS of oh8dG-positive cells in the animals treated with FCIR of 90/60. No terminal UTP nicked-end labeling (TUNEL)-positive cells, as a detection of cell death, were detected at this early reperfusion time. Our data suggest that early oxidative DNA lesions elicited by experimental stroke could be repaired. Therefore, the oxidative DNA lesions observed in the nuclear and mitochondrial DNA of the brain are different from the DNA fragmentation detected using TUNEL.
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PMID:Oxidative DNA damage precedes DNA fragmentation after experimental stroke in rat brain. 1078 50

Oxidative stress has been reported to be involved in not only cardiovascular diseases but in hypertension, which is a major risk for cardiovascular diseases. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been recognized as a sensitive biomarker of oxidative DNA damage and also of oxidative stress. In the present study, we assessed the oxidative stress in human subjects with hypertension and in hypertensive rats. In stroke-prone spontaneously hypertensive rats at the age of 14 weeks, the excretion of urinary 8-OHdG was significantly (p < 0.05) increased compared with that in age-matched normotensive Wistar-Kyoto rats. Next, we investigated the relationship between oxidative DNA damage and cardiovascular risk factors among Tanzanians aged 46-58 years in a population study carried out in 1998 in at Dar es Salaam, Tanzania, according to the WHO-CARDIAC Study Protocol. Sixty subjects (male/female, 28/32) were selected by SPSS Base 8.0 from those who completed a 24-h urine collection. The 24-h urinary 8-OHdG of the hypertensive subjects (SBP > or =140 mmHg and/or DBP > or =90 mmHg) was significantly (p < 0.05) higher than that of the normotensive subjects (SBP <140 mmHg and DBP <90 mmHg) after adjusting for age and gender (Hypertensives: 17.31 +/- 2.0 ng/mg creatinine, n=38; Normotensives: 10.10 +/- 2.64 ng/mg creatinine, n=22). Oxidative stress was thought to be involved in hypertensive subjects and in hypertensive rats.
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PMID:Assessment of in vivo oxidative stress in hypertensive rats and hypertensive subjects in Tanzania, Africa. 1082 Nov 40

1. In the present study, we examined the effect of resveratrol (3,4',5-trihydroxystilbene), a phytoestrogen found in the skins of most grapes, on oxidative DNA damage in male and female stroke-prone spontaneously hypertensive rats (SHRSP). 2. Five-week-old male and female SHRSP were divided into control and resveratrol groups. The resveratrol group was given 1 mg/kg per day, orally, resveratrol by gastric intubation once a day. 3. Following an 8 week feeding period, the levels of 8-hydroxydeoxyguanosine (8-OHdG), produced from deoxyguanosine under conditions of oxidative stress, in the urine of male and female resveratrol-treated SHRSP were significantly lower than that in control SHRSP. 4. The urine of resveratrol-treated male and female SHRSP had lower levels of hydroperoxide compared with control SHRSP, but the difference was not significant. 5. Treatment with resveratrol resulted in a 25 and 30% reduction in plasma glycated albumin in male and female SHRSP, respectively, compared with controls. 6. Gender differences for SHRSP with regard to 8-OHdG, hydroperoxide and glycated albumin levels were not confirmed, resveratrol having similar protective effects on male and female SHRSP. 7. These results indicate that dietary resveratrol: (i) plays a role in suppressing oxidative DNA damage and glycoxidative stress in vivo; and (ii) has similar protective effects in both male and female SHRSP, suggesting that the direct effects of this phytoestrogen on oxidative stress in vivo are not sexually dimorphic.
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PMID:Protective effect of resveratrol on oxidative damage in male and female stroke-prone spontaneously hypertensive rats. 1115 37

The preventive effects of sesamin, a lignan from sesame oil, and vitamin E on hypertension and thrombosis were examined using stroke-prone spontaneously hypertensive rats (SHRSP). At 5 weeks of age the animals were separated into four groups: (i) a control group; (ii) a vitamin E group, which was given a 1,000 mg alpha-tocopherol/kg diet; (iii) a sesamin group, given a 1,000 mg sesamin/kg diet; and (iv) a vitamin E plus sesamin group, given a 1,000 mg alpha-tocopherol plus 1,000 mg sesamin/kg diet for 5 weeks from 5 to 10 weeks of age. Resting blood pressure was measured by the tail-cuff method once weekly. A closed cranial window was created and platelet-rich thrombi were induced in vivo using a helium-neon laser technique. The number of laser pulses required for formation of an occlusive thrombus was used as an index of thrombotic tendency. In control rats, systolic blood pressure and the amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) became significantly elevated with age. However, the elevation in blood pressure and 8-OHdG were significantly suppressed in rats administrated vitamin E, sesamin, or vitamin E plus sesamin. At 10 weeks, the number of laser pulses required to induce an occlusive thrombus in arterioles of the control group was significantly lower than in the other groups (p<0.05). These results indicate that chronic ingestion of vitamin E and sesamin attenuated each of elevation in blood pressure, oxidative stress and thrombotic tendency, suggesting that these treatments might be beneficial in the prevention of hypertension and stroke.
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PMID:Effects of vitamin E and sesamin on hypertension and cerebral thrombogenesis in stroke-prone spontaneously hypertensive rats. 1176 36

1. An extract of Ginkgo biloba (EGb 761) has been reported to alleviate cerebrovascular problems. In the present study, we investigated the antithrombotic effects of EGb 761 in cerebral blood vessels of stroke-prone spontaneously hypertensive rats (SHRSP/Izm). 2. In the present study, EGb 761 was administered orally to SHRSP/Izm at 60 and 120 mg/kg each day for 3 weeks from the age of 7 weeks. The age-related increase in blood pressure observed in SHRSP was suppressed significantly by EGb 761 at both doses 3 weeks after treatment. 3. Thrombotic potential was assessed in vivo using a He-Ne laser-induced thrombosis model and was significantly suppressed by EGb 761. 4. The anti-oxidant effects of EGb 761 were determined by measurement of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). At 120 mg/kg, EGb 761 decreased 8-OHdG significantly compared with control animals. 5. Urinary nitrite/nitrate, nitric oxide (NO) metabolites, were increased significantly after administration of EGb 761. Expression of endothelial NO synthase (eNOS) mRNA was measured using a real-time quantitative reverse transcription-polymerase chain reaction method. The expression of eNOS mRNA in the EGb 761 group (120 mg/kg) was significantly higher than in the control group. 6. The results indicate that EGb 761 decreases blood pressure and mediates strong antithrombotic and anti-oxidant effects in SHRSP. These pharmacological activities may contribute to the beneficial properties of EGb 761 observed in clinical practice.
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PMID:Effects of Ginkgo biloba extract (EGb 761) on cerebral thrombosis and blood pressure in stroke-prone spontaneously hypertensive rats. 1236 86

The antioxidant and neuroprotective potential of the glutathione peroxidase mimic ebselen has been investigated in experimental stroke. Intravenous ebselen (1 mg/kg/h) or vehicle infusion was started 45 min before permanent middle cerebral artery occlusion in the rat, and continued until the end of the experiment. The topography and extent of oxidative damage to the brain was assessed immunohistochemically using an antibody for DNA damage that identified hydroxylated products of 2'-deoxyguanosine (8-OHdG/8-oxodGuo) and an antibody for lipid peroxidation that identified the 4-hydroxynonenal histidine adduct (4-HNE). Ischemic damage was mapped and evaluated with standard histopathology. In the vehicle-treated rats immunopositive staining for both 8-oxodGuo and 4-HNE extended beyond the boundary of ischemic damage. In ebselen-treated rats, the extent of tissue immunopositive for 8-oxodGuo, and 4-HNE was less than that demonstrating ischemic damage confirming the antioxidant mechanism of action in vivo. In addition, ebselen treatment induced a 28% reduction in cortical ischemic damage (p <.02).
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PMID:Antioxidant ebselen reduces oxidative damage in focal cerebral ischemia. 1249 79

The preventive effects of sesamin, a lignan from sesame oil and vitamin E on hypertension and thrombosis were examined using stroke-prone spontaneously hypertensive rats (SHRSP). Animals at 5 weeks of age were separated into four groups: (i) control group; (ii) vitamin E group, which was given 1000 mg alpha-tocopherol/kg diet; (iii) sesamin group, given 1000 mg sesamin/kg diet; and (iv) vitamin E plus sesamin group, given 1000 mg alpha-tocopherol plus 1000 mg sesamin/kg diet for 5 weeks from 5 to 10 weeks of age. Resting blood pressure was measured by the tail-cuff method once weekly. A closed cranial window was created in the right parietal bone of the rat and platelet-rich thrombi were induced in vivo using a helium-neon laser technique. The number of laser pulses required for formation of an occlusive thrombus was used as an index of thrombotic tendency. In control rats, systolic blood pressure and the amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) became significantly elevated with age. However, the elevation in blood pressure and 8-OHdG were significantly suppressed in rats administered vitamin E, sesamin, or vitamin E plus sesamin. At 10 weeks, the number of laser pulses required to induce an occlusive thrombus in arterioles of the control group was significantly lower than in the other groups (P < 0.05). These results indicate that chronic ingestion of vitamin E and sesamin attenuated both elevation in blood pressure, oxidative stress and thrombotic tendency, suggesting that these treatments might be beneficial in the prevention of hypertension and stroke.
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PMID:Effects of vitamin E and sesamin on hypertension and cerebral thrombogenesis in stroke-prone spontaneously hypertensive rats. 1564 79

1. Effects of voluntary exercise on blood pressures, oxidative stress, urinary nitric oxide (NO) level and expression of endothelial NO synthase (eNOS) mRNA were studied in stroke-prone spontaneously hypertensive rats (SHRSP/Izm). 2. SHRSP at the age of 6 weeks were divided into four groups: (i) the control group, sedentary group; (ii) the L-NAME group, which was the sedentary control group given L-NAME (5 mg/kg per day) in drinking water; (iii) the exercise group, which was allowed to run voluntarily on running wheel attached to the metal cages; and (iv) the exercise plus L-NAME group which was loaded exercise and given L-NAME solution for 3 weeks. 3. The bodyweight and systolic pressure of rats were increased with age and the bodyweight of the rats in an exercise plus L-NAME group was less than control but systolic pressure in the exercise group were significantly lower than control. 4. Thrombotic tendency assessed by He-Ne laser method in an exercise group was significantly decreased compared with the rest of the groups. 5. Urinary nitrite/nitrate level was significantly increased in the exercise group compared with before (6 weeks) and after exercise (9 weeks), but there were no significant differences in the rest of groups. 6. eNOS mRNA expression of aorta in the exercise group measured after exercise was significantly higher than the other groups. 7. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) level after exercise was significantly decreased in the exercise group compared with before exercise. 8. These results suggested that voluntary exercise decreased thrombotic tendency by increasing NO level through enhanced expression of eNOS mRNA and antioxidative effects.
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PMID:Effects of voluntary exercise on cerebral thrombosis and endothelial function in spontaneously hypertensive rats (SHRSP/Izm). 1564 88


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