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1.
The effect of alcohol intoxication on regional cerebral blood flow (rCBF) is unclear. The few published studies provide a mixed picture of alcohol effects, suggesting that blood flow increases at low doses and decreases at higher doses of alcohol. Using the cerebral blood flow agent 99mtechnetium hexamethyl-propylene-amine-oxime (HMPAO) and image reconstruction with single photon emission computed tomography (SPECT), we evaluated the effect of an oral dose of ethanol (0.6 g/kg) on rCBF in two age-stratified groups of healthy, nonalcoholic men (12 age 22–37 and 12 age 63–77). Intoxication was associated with a significant 4% increase in global cortical CBF ( t = 2.54, p = 0.02). Changes in HMPAO uptake were negatively correlated to ethanol levels in the entire group ( r = -0.47, p = 0.04). This relationship was seen in the older subgroup ( r = -0.70, p = 0.05), but not in the younger group ( r = -0.34, p = 0.26). In contrast, the younger group showed a significant positive correlation between rCBF and increases in acetate levels ( r = 0.71, p < 0.01), which was not seen in the older group ( r = -0.02, p = 0.96). These findings suggest that both acetate and alcohol contribute to the changes in CBF seen in the intoxication syndrome and that their relative influence is age-dependent.  相似文献   

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In the normal adult brain, glucose provides 90% of the energy requirements as well as substrate for nucleic acid and lipid synthesis. In the present study, effects of ethanol on glucose transporters (GLUT) and glucose utilization were examined in rat brain. Male Sprague-Dawley rats weighing 250-300 gms were given either ethanol 3 gm/kg BW or saline IP 4 hrs prior to the animal sacrifice and removal of the cerebral cortical tissue. The cortical plasma membranes analyzed by cytochalasin B binding assay showed a decrease in GLUT number but not in GLUT affinity in the ethanol treated rats as compared to the control rats. The estimated Ro values were 70 ± 8.9 Vs 91 ± 8.9 pmoles/mg protein (p < 0.05 N=4) and the estimated Kd values were 0.37 ± 0.03 and 0.28 ± 0.05 M (p: NS) in ethanol and control experiments respectively. Immunoblots of purified cerebral plasma membranes and low density microsomal fraction showed 17% and 71% decrease for GLUT1 and 54% and 21% (p<0.05 or less; n=6) for GLUT3 respectively in ethanol treated rats than in control animals. Immunofluoresence studies also showed reduction of GLUT1 immunoreactively in choroid plexus and cortical microvessels of ethanol treated rats as compared to control rats. The effect of ethanol on regional cerebral metabolic rates for glucose (CMRGle) was studied using [6-14C] glucose and showed statistically insignificant decrease in brain glucose utilization. These data suggest that ethanol invivo decrease GLUT number and protein content in rat cerebral cortex  相似文献   

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BACKGROUND: This study evaluated hypotheses concerning alcoholism, aging, and the relationship between cerebral hypoperfusion and residual deficits in the functioning of cerebellar and neocortical brain systems. METHODS: The participants were 10 healthy abstinent alcoholics (9 men, 1 woman) and 12 nonalcoholic controls (10 men, 2 women) ranging in age from 35 to 67 years. Cerebral blood flow was observed through the use of regionally specific computer-derived quantitative analysis of single photon emission computed tomography (SPECT) perfusion images. Cerebellar perfusion was measured and compared with cerebral cortex perfusion in age-equivalent subgroups of alcoholics and controls (under 55 years; 55 years and over). RESULTS: In abstinent alcoholics under age 55, cerebellar perfusion ratios were significantly reduced compared with the controls. In alcoholics and nonalcoholic controls 55 years old and older, this relationship was reversed, probably as a result of diminished cortical perfusion with aging in the alcoholics and of cerebellar decline in the controls. CONCLUSIONS: The findings support hypotheses that the residual effects of alcoholism include cerebellar brain abnormalities and that aging combined with long-term alcoholism leads to cerebral cortical decline.  相似文献   

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目的 探讨慢性进展性大脑中动脉主干闭塞患者的临床、神经影像和脑血流动力学改变.方法 对75例大脑中动脉主干闭塞患者行头颅核磁共振成像、CT和经颅多普勒超声检测.结果 65例(86.7%)出现脑缺血症状及体征.70例(93.3%)头颅核磁共振或CT显示不同类型脑梗死,最常见的是低灌注分水岭梗死和腔隙性脑梗死.60例(80.0%)闭塞侧大脑中动脉深度范围血流速度明显降低,70例(93.3%)闭塞侧大脑前动脉血流速度代偿性增快,45例(60.0%)闭塞侧大脑后动脉血流速度代偿性增快.结论 经颅多普勒超声和神经影像学检查有助于评估慢性进展性大脑中动脉主干闭塞患者的病情发展和预后,为了解颅内侧支循环代偿状况和更深入研究缺血性脑血管病的发病机制提供客观依据.  相似文献   

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Intercellular communication in the liver is a potentially important mechanism for the regulation of hepatic metabolism. Since alcohol (ethanol, ETOH) can interact with both parenchymal and nonparenchymal cells, the present study was performed to assess the possible effects of ETOH on the nonparenchymal cell-to-hepatocyte signal traffic by studying the glycogenolytic and glycolytic response of the perfused rat liver to colloidal carbon, a phagocytic stimulus for Kupffer and sinusoidal endothelial cells. Livers from fed rats were perfused with hemoglobin-free Krebs Ringer bicarbonate buffer containing ETOH (20 mm) or acetaldehyde (1 mm). Twenty minutes after initiating the infusion of ETOH or acetaldehyde, colloidal carbon was infused and the rate of carbon uptake, glucose, lactate and pyruvate output, and oxygen consumption were determined. In control livers, carbon stimulated the output of glucose (60%), lactate (25%), and pyruvate (53%), without affecting the lactate/pyruvate ratio. ETOH, but not acetaldehyde, enhanced the carbon effect on glucose output (38%), but suppressed the increased lactate and pyruvate output (48% and 91% respectively) resulting in a dramatic 10-fold increase in the lactate/pyruvate ratio. By using inhibitors of cyclooxygenase or alcohol dehydrogenase (indomethacin and 4-methylpyrazole, respectively) in the presence of carbon and/or ETOH, we determined that: (1) following carbon stimulation prostaglandins are the likely mediators secreted by nonparenchymal cells that increase carbohydrate output; and (2) the ETOH-induced enhancement of carbonstimulated glycogenolysis is also mediated by prostaglandins and is not dependent on the oxidative metabolism of ETOH.  相似文献   

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It has been reported that cerebral blood flow is decreased in chronic alcoholics without neurological diseases. We performed SPECT by the resting and vascular reserve (RVR) method in 11 chronic alcoholics (mean age 59.1 ± 10.4, all males) and 11 age-matched healthy controls (mean age 58.8 ± 10.1, all males). The resting and vascular reserve (RVR) method is a consecutive 99mTc-ECD SPECT study before and after acetazolamide administration with adjunctive radionuclide angiography, which is easy to perform for a routine clinical study and quite useful for evaluating regional cerebral blood flow and the cerebrovascular response to acetazolamide. Regional cerebral blood flows in almost all regions in the alcoholic group were lower than those in the control group. However, there were no significant differences in increased rates of blood flow in response to acetazolamide in almost all regions between the chronic alcoholic group and the control group. In both groups, the increased rates of blood flow in response to acetazolamide in the supratentorial region, cerebellum, and brain stem were 30–40%, 20–25%, and 42–48%, respectively. The cerebrovascular response to acetazolamide in chronic alcoholics was not impaired, therefore the reduction of brain metabolism may be one of the important factors causing the decreased cerebral blood flow in chronic alcoholics.  相似文献   

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The quantitative autoradiographic 2-[14C]deoxyglucose method was used to measure the effects of the acute administration of ethanol on local rates of glucose utilization in male Sprague-Dawley rats. Rates of glucose utilization were measured 10 min after the intraperitoneal administration of 0.00, 0.25, 0.50, and 1.00 g/kg ethanol. The acute administration of the lowest dose of ethanol (0.25 g/kg) significantly increased rates of cerebral metabolism, as compared with vehicle-treated controls, in structures of the mesocorticolimbic and nigrostriatal dopaminergic systems. Among the affected regions were the nucleus accumbens, medial prefrontal cortex, olfactory tubercle, caudate, ventral tegmental area, and substantia nigra. Acute administration of 0.50 g/kg ethanol resulted in similar trends in increased functional activity; however, significant increases were limited to the somatosensory cortex, posterior nucleus accumbens, and the CA3 region of the hippocampus. In contrast, the administration of 1.00 g/kg ethanol produced widespread decreases in rates of glucose utilization in brain regions involved in processing of sensory and motor information, as well as in portions of the limbic system. These data indicate that the effects of acute ethanol administration on functional activity as reflected by rates of glucose utilization are dose-dependent. These cerebral metabolic effects parallel the dose-dependent effects of ethanol on motor behavior, with stimulatory effects generally observed at lower doses and depressive effects at higher doses. Moreover, each of the doses studied produced alterations in functional activity in a unique subset of structures. This suggests that different neuroanatomical circuits mediate the effects of each dose.  相似文献   

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Background: A low level of response (LR) to alcohol is an important endophenotype associated with an increased risk of alcoholism. However, little is known about how neural functioning may differ between individuals with low and high LRs to alcohol. This study examined whether LR group effects on neural activity varied as a function of acute alcohol consumption. Methods: A total of 30 matched high‐ and low‐LR pairs (N = 60 healthy young adults) were recruited from the University of California, San Diego, and administered a structured diagnostic interview and laboratory alcohol challenge followed by two functional magnetic resonance imaging (fMRI) sessions under placebo and alcohol conditions, in randomized order. Task performance and blood oxygen level‐dependent response contrast to high relative to low working memory load in an event‐related visual working memory (VWM) task were examined across 120 fMRI sessions. Results: Both LR groups performed similarly on the VWM task across conditions. A significant LR group by condition interaction effect was observed in inferior frontal and cingulate regions, such that alcohol attenuated the LR group differences found under placebo (p < 0.05). The LR group by condition effect remained even after controlling for cerebral blood flow, age, and typical drinking quantity. Conclusions: Alcohol had differential effects on brain activation for low‐ and high‐LR individuals within frontal and cingulate regions. These findings represent an additional step in the search for physiological correlates of a low LR and identify brain regions that may be associated with the low LR response.  相似文献   

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Selective breeding of rats for sensitivity to the anesthetic effects of ethanol is being carried out with rats derived from the genetically heterogeneous N/Nih stock. Thirteen generations of within family selection have been achieved with replicate high (HAS), low (LAS) and control alcohol sensitive (CAS) lines. Significant separation between lines on sleep time and blood ethanol concentration (BEC) at awakening following ethanol administration has been achieved. In general, the results obtained so far replicate the findings with short (SS) and long (LS) sleep mice. One exception is that the high alcohol sensitivity rats (HAS) also appear more sensitive to pentobarbital relative to LAS rats. This finding is opposite to that which occurs with SS and LS mice where the low ethanol sensitive SS mice appear more sensitive to pentobarbital than the LS mice.  相似文献   

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目的探讨分次不同角度头高斜位暴露下,正常人体心血管反射与调节特征,从而筛选出有效的倾斜试验生理评价指标和最佳技术方案,为飞行员专项医学选拨和鉴定服务.方法采用自行研制的多功能双向式医用倾斜床,结合十二导联同步心电图描记方法和经颅多普勒脑血流成像技术,对20名健康自愿者进行分次不同角度(+60°/次、+75°/次、+90°/次)头高斜位暴露下的心率、血压、心率变异(HRV)和脑血流速率的测量与分析.结果①与暴露前比较暴露后心率明显增快,平均RR间期和脉压差明显缩小,有显著性差异(P<0.05~0.01);RR间期标准差在+75°20′和+90°20′明显缩小,有显著性差异(P<0.05);心率变异系数在+90°明显缩小,有显著性差异(P<0.05);收缩压除+60°即刻外均明显下降,有显著性差异(P<0.05~0.01);舒张压在20′时段明显升高,有非常显著性差异(P<0.01);收缩期最大血流速率在+60°20′和+75°即刻、+75°20′、+90°20′均明显下降,有非常显著性差异(P<0.01);平均血流速率除+90°即刻外均明显下降,有显著性差异(P<0.05~0.01).②各角度间比较心率和HRV指标在+75°和+90°均较+60°变化明显,有显著性差异(P<0.05~0.01),多项脑血流指标在+75°均较另外两个角度变化显著,有显著性差异(P<0.05~0.01).结论同一组个体分次不同角度暴露下心率、血压、HRV和脑血流变化特征和规律各异,但均以+75°头高斜位下表现最明显和最具规律性.  相似文献   

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Neurons in the rat hippocampal formation (the dentate gyrus and the hippocampus) are born over a protracted period, from gestational day (G) 15 into adulthood. Dentate gyral neurons born prenatally are generated from the ventricular zone, whereas those born postnatally are derived from a secondary proliferative zone, the intrahilar zone. In contrast, hippocampal pyramidal neurons are generated only prenatally from the ventricular zone. In the neocortex, ethanol depresses the proliferation of cells in the ventricular zone and stimulates the proliferation of cells in the secondary proliferative zone. The present study tests the hypotheses that prenatal treatment with ethanol has a different effect on the generation of dentate gyral neurons than does postnatal ethanol treatment, and that these differences are determined by the timing of the ethanol exposure relative to the period and site of neuronal generation. Rats were treated with ethanol between G6 and G21 or between postnatal day (P) 4 and P12. They were given an injection of [3H]thymidine on G15, G18, G21, P6, P9, or P12. Rats were killed on P30–P35. The tissue was processed by standard autoradiographic methods and assessed using rigorous stereological procedures. The total number of neurons and the density of radiolabeled neurons in both the dentate gyrus and the CA1 region of the hippocampus were determined. Prenatal ethanol treatment decreased the total number of neurons in the CA1 segment of the hippocampus and had little impact on neuronal number in the dentate gyrus. Likewise, the number of hippocampal and dentate gyral neurons generated daily was significantly lower in ethanol-treated rats than in controls. Postnatal treatment to ethanol, however, significantly increased the total number of dentate gyral neurons and the density of neurons generated postnatally. These postnatal changes depended on the blood ethanol concentration (BEC). At moderate BECs, the total number of neurons in the dentate gyrus and the number of neurons generated was increased. At high BECs, however, neuronal number and neuronal generation were decreased. Postnatal ethanol treatment had no effect on the number of (total or radiolabeled) CA1 neurons. Thus, pre- and postnatal exposure to ethanol have opposite effects both on the number of neurons in the dentate gyrus and on the generation of neurons. These paradoxical effects likely result from three causes: the differential effects of ethanol on the two proliferative zones, the critical period of neuronal development, and the potentially opposite effects of moderate and high BEC.  相似文献   

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目的 :研究养心氏片对急性脑梗死病人血液流变学和脑血流量的影响。方法 :选择 10 0例急性脑梗死病人 ,随机分为养心氏片组 (治疗组 ) 5 2例和对照组48例 ,两组均予复方丹参注射液2 0ml加生理盐水 2 5 0ml静脉输注 ,每日 1次 ;治疗组另加养心氏片 ,每次 5片 ,每日 3次口服 ,两组均治疗 2周。结果 :养心氏治疗组总有效率为 84% ,对照组为5 9 % ,两组比较有统计学意义(P <0 .0 5 )。两组治疗后血液流变学指标和脑血流量均有所改善 ,治疗组和对照组血浆比黏度差分别为 ( -0 .3 0± 0 .3 6)和( -0 .17± 0 .10 ) ;血小板黏附率分别为 ( -14 .1± 1.77) %和( -6.2± 1.4) % ,以治疗组尤为明显 (P <0 .0 5和P <0 .0 1)。结论 :养心氏片能有效改善病人血液流变学和脑血流量。  相似文献   

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The effects of ethanol on the cell cycle kinetics of cortical precursor cells during the period of cortical neuronogenesis [between gestational day (G) 12 and G21] was systematically examined. Samples of dissociated cortical cells were harvested from the cerebral cortices of 13-, 15-, 17-, 19-, and 21-day-old fetuses. The fetuses were obtained from pregnant rats: (a) fed a liquid diet containing 6.7% (v/v) ethanol (Et) ad libitum, (b) pair-fed an Isocaloric liquid control diet (Ct), or (c) fed chow and water (Ch) ad libitum. Before harvesting the cells, the fetuses were administered a series of 1–5 injections of bromodeoxyuridine (BrdU). The proportion of cells that incorporated the BrdU was assessed. Using these raw data, the S-phase length (TB, total cell cycle length (Tc), and the growth fraction (GF; the fraction of the total population that was actively cycling) were determined with a cumulative labeling procedure. The T3 was –8–9 hr, regardless of either the date of the injection or the dietary treatment of the dam. On the other hand, the Tc for the Ct- and Ch-treated rats increased over the gestational period. That is, the Tc was shortest on G13 and longest on G21. The Tc for Et-treated rats, however, did not change between G13 and G21. For the Ch- and Ct-treated groups, the GF decreased > 15-fold between G13 and G21. The decline (5-fold) for the Et-treated group over the same period, however, was not as great as it was for the Ct-treated fetuses. Thus, by G17 (and thereafter), the GF for Et-treated fetuses was significantly greater than it was for the Ct-treated group. Ethanol treatment has opposite effects on the two cortical germinal zones; it stimulates the proliferation of subventricular cells, whereas it inhibits the proliferation of ventricular cells). Thus, the ethanol-induced changes in the Tc and the GF reflect the combined effects of ethanol on the two cortical proliferative zones.  相似文献   

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Dose-response effects of acute ethanol infusions were studied, noninvasively, in the unopened brain to examine the hypothesis that ethanol can induce stroke-like events as a consequence of cerebral vasospasm and tissue ischemia. By using a single sending and receiving fiber, an optical backscatter measurement (500–800 nm) was used to monitor the levels of deoxyhemoglobin (DH), reduced cytochrome oxidase (rCO), and relative tissue blood content in a closed cranium preparation. Anesthetized rats were prepared by cannulating a branch of the internal carotid artery and subjected to either bolus infusions (1.25 or 2.5 μm ethanol in Ringers/g tissue) or to constant infusions of 5 or 10% ethanol at various rates (0.30–2.92 μm /g/min). To facilitate optical penetration, a portion of the left parietal cranium was shaved to a translucent appearance. Results showed that low, bolus doses of ethanol typically produced a slight increase (5–10%) in the oxyhemoglobin signal, indicating that vasodilation had probably occurred. Higher doses, however, produced a prompt and significant reduction in the hemoglobin signal, increased levels of DH, and a rise in rCO suggesting a vasoconstrictor response leading to ischemia had occurred, followed by recovery within 3–5 min. Constant infusions of ethanol produced a similar cerebral vascular response, in a dose-related manner, but of a more sustained nature. At levels of 50–60% of the maximum bolus dose, the effect was more pronounced, accompanied by an increase in the levels of rCO (by 50–90%). Control experiments using identical volumes/flow rates of Ringers solution produced no significant alterations in the optical spectrum. Overall, these data indicate that, depending on dose: (a) ethanol can induce vasodilatory or vasoconstrictor effects in the intact brain; (b) the more pronounced effects involve vasospasm in the cortical microcirculation leading to global ischemia; and (c) optical measurements permit direct noninvasive assessment of the cerebral vascular effects of alcohol and, potentially, other substances of abuse  相似文献   

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The rat is widely used as an animal model for experiments involving ethanol, and alcohol concentrations in blood obtained from the tail routinely are used to monitor ethanol exposure and metabolism. The present study demonstrates that during periods of rising and declining ethanol levels, the alcohol concentrations in tail vein blood lags far behind that of arterial, jugular, or femoral vein blood. As a result, tail vein ethanol concentrations markedly underestimate the concentration in arterial blood and rapidly perfused tissue during periods of increasing body ethanol, whereas the reverse is true as body ethanol declines. This discrepancy, which appeared to result from the low blood perfusion:tissue water ratio in the tail, disappeared when the tail was heated to 37°C. Compared with arterial blood, alcohol measurements performed on tail vein blood yielded a much higher apparent Km for ethanol clearance and a somewhat lower estimate of ethanol reaching the peripheral circulation. We conclude that, for a variety of studies, analyses of arterialized blood from the heated tail should yield a more accurate and reproducible measure of ethanol exposure and/or metabolism than does the conventional collection from the unheated tail.  相似文献   

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