bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased cerebral lactate output to cerebral venous blood after forebrain ischemia in rats.
Authors: Frerichs K U , Lindsberg P J , Hallenbeck J M , Feuerstein G Z
Published: June 2011

Increased cerebral lactate levels are a well-known aspect of the sequelae of the metabolic derangements that follow cerebral ischemia. A new technique has recently become available to sample cerebral venous blood from the superior sagittal sinus on a long-term basis in conscious rats. We report the applicability of this method to assess serial biochemical responses to brain injury. Serum samples were obtained from the superior sagittal sinus, the common carotid artery, and the external jugular vein of nine anesthetized rats before and up to 7 days after 10 minutes of forebrain ischemia was produced by carotid occlusion and hypovolemic hypotension (mean arterial blood pressure 50 +/- 4 mm Hg). The cerebral venous-arterial difference in serum lactate concentration was increased for up to 3 hours after ischemia, while there was no significant change in the difference in serum lactate concentrations in the common carotid artery and the external jugular vein. This indicates an elevated output of lactate from brain tissue to blood, detectable only in the superior sagittal sinus, which underlines the usefulness of the technique. We observed a persistent elevation in brain lactate production after virtually complete recovery from the acute insult.
Incidence of hypertension and stroke in relation to body fat distribution and other risk factors in older women.
Authors: Folsom A R , Prineas R J , Kaye S A , Munger R G
Published: June 2011

The relation between body fat distribution, as measured by the waist-to-hip circumference ratio, and the 2-year incidences of hypertension and stroke were examined in a cohort of 41,837 women aged 55-69 years. Women who developed hypertension were 2.1 (95% confidence interval 1.7-2.6) times more likely to be in the upper tertile of waist-to-hip ratio than those who did not. Adjustment for age, body mass index (kilograms per meter squared), cigarette smoking, physical activity, alcohol intake, and education level reduced this odds ratio to 1.6 (95% confidence interval 1.3-2.1). Women who developed a stroke were also 2.1 (95% confidence interval 1.5-2.9) times more likely to be in the upper tertile of waist-to-hip ratio than those who did not. Adjustment for the same covariates also lowered this odds ratio to 1.6 (95% confidence interval 1.1-2.4). Further adjustment for hypertension and diabetes mellitus reduced the estimated risk of stroke due to elevated waist-to-hip ratio to 1.3 (95% confidence interval 0.8-2.1). Hypertension, diabetes mellitus, and cigarette smoking remained significantly associated with stroke incidence in the multivariate model. These results indicate that abdominal adiposity, as measured by an increased waist-to-hip ratio, increases the risks of hypertension and stroke, even after accounting for overall body mass. The association of abdominal adiposity with risk of stroke is related, in part, to the association of abdominal adiposity with hypertension and diabetes.
Duration of cigarette smoking is the strongest predictor of severe extracranial carotid artery atherosclerosis.
Authors: Whisnant J P , Homer D , Ingall T J , Baker H L , O'Fallon W M , Wievers D O
Published: June 2011

The effect of cigarette smoking on extracranial carotid atherosclerosis was studies by obtaining cigarette smoking histories and information on other potential risk factors from consecutive patients undergoing carotid arteriography. At least on extracranial carotid artery was visualized in 752 patients in whom the extent of carotid atherosclerosis was assessed. The total years of cigarette smoking was the most significant independent predictor of the presence of severe carotid atherosclerosis. Other independent predictors, in order of significance, were age, hypertension, diabetes mellitus, male sex, and current systolic blood pressure. By age 60 years, the risk of having severe carotid atherosclerosis for a person who had smoked for 40 years was approximately 3.5 times that for a never smoker. The major benefit of smoking cessation is in limiting the accumulation of smoking years.
Problems in cerebral blood flow calculation using xenon-133 in patients with pulmonary diseases.
Authors: Hansen M , Jakobsen M , Enevoldsen E , Egede F
Published: June 2011

We used the end-tidal concentration of xenon-133 (air curve) to estimate the profile of its arterial concentration in calculating cerebral blood flow. We examined the effects of pulmonary disease and artificial ventilation on the air curve and the calculated cerebral blood flow. We studied the relation between arterial and end-tidal xenon activities in 19 subjects, of whom 15 had pulmonary dysfunction. The t 1/2 of the declining phases of the arterial and air curves were used to express their shapes. The mean +/- SD reference t 1/2 from 15 normal volunteers was 26.8 +/- 8.4 seconds. The mean +/- SD t 1/2 s of the air and arterial curves from the 15 patients with pulmonary dysfunction were 10.4 +/- 2.9 and 33.8 +/- 10.9 seconds. The degree of pulmonary dysfunction (expressed as the pulmonary shunt percentage) correlated with distortion of the air curve. Substituting the arterial for the air curve, mean calculated cerebral blood flow (as the initial slope index) increased from 40 to 61 for the 12 patients with chronic obstructive pulmonary disease. The degree of underestimation of cerebral blood flow using the air curve correlated with the pulmonary shunt percentage. Our work confirms the problems of estimating cerebral blood flow in subjects with pulmonary dysfunction.
Treatment of right hemispheric cerebral infarction by hemicraniectomy.
Authors: Delashaw J B , Broaddus W C , Kassell N F , Haley E C , Pendleton G A , Vollmer D G , Maggio W W , Grady M S
Published: June 2011

An anecdotal series of nine patients (three men and six women with an average age of 57 years) presented with progressive neurologic deterioration while on medical therapy for large right hemispheric cerebral infarction. Clinical signs of uncal herniation (anisocoria or fixed and dilated pupils, and/or left hemiplegia with right decerebrate posturing) were present in seven of these nine patients. Computerized tomography of the head confirmed mass effect from cerebral edema. It was the clinical judgment of the treating neurologists and neurosurgeons that each of these nine patients would perish unless surgical decompression of the infarcted brain was performed. Accordingly, each was treated with right hemicraniectomy and dural augmentation. Six patients demonstrated neurologic improvement on the first postoperative day. One patient, with a postoperative diagnosis of lung cancer, died 1 month after surgery. The remaining eight patients are currently living with their families with a follow-up period ranging from 5 to 25 months. Patient outcome as evaluated by the Barthel Index indicates that three individuals are functioning with minimal assistance and that the remaining six patients are functionally dependent. After rehabilitative therapy, four patients returned for elective cranioplasty. These results suggest that hemicraniectomy can be an effective lifesaving procedure for malignant cerebral edema after large hemispheric infarction.
Lidocaine accelerates neuroelectrical recovery after incomplete global ischemia in rabbits.
Authors: Rasool N , Faroqui M , Rubinstein E H
Published: June 2011

The use of high-dose lidocaine for cerebral protection during ischemia has produced varied results. Our study uses a new, single carotid artery preparation in the rabbit to produce incomplete global ischemia by graded carotid occlusion; specific electroencephalographic changes are used as the end point for the extent of blood flow reduction sustained during 20 minutes. We monitored arterial pressure, intracranial pressure, and internal carotid blood flow that were recorded with an electromagnetic flowmeter after surgical ligation of the opposite internal and the two vertebral arteries, and we studied the electroencephalogram and somatosensory-evoked potentials elicited by stimulation of the sciatic nerve. Low-dose lidocaine (0.2 mg/kg/min) infused throughout the experiment significantly accelerated the time course of the return of electroencephalographic and evoked-potential amplitudes toward control. Deep halothane anesthesia alone elicited the slowest recovery, suggesting that the action of lidocaine was independent of its general anesthetic effect. There were very small differences among the groups in the measured arterial pressure, intracranial pressure, and cerebral blood flow, suggesting that lidocaine changed recovery rate without markedly modifying any characteristic of the postischemic cerebral perfusion. The protective effect of lidocaine may be the result of a specific blockade of Na+ channels or a decrease in excitatory neurotransmitter release, either of which would cause a delay in the onset of the events that lead to neuronal damage during ischemia.
Spontaneous improvement after acute ischemic stroke. A pilot study.
Authors: Biller J , Love B B , Marsh E E , Jones M P , Knepper L E , Jiang D , Adams H P , Gordon D L
Published: June 2011

Recent clinical studies emphasize the importance of early (less than 12 hours after onset) treatment of patients with acute ischemic stroke. Therapies have been proposed as being effective because of early clinical improvement. The frequency and degree of spontaneous improvement in such patients, however, is unknown. We prospectively evaluated the course of 29 patients (19 men, 10 women) aged 33-82 years who were seen less than or equal to 12 hours after the onset of acute ischemic stroke. Seventeen patients were first evaluated less than or equal to 6 hours and the remaining patients at 6-12 hours after onset. All patients were examined using a modified National Institutes of Health Stroke Scale at baseline, 1, 2, 3, and 6 hours. No specific treatment for acute ischemic stroke was given during this time. Improvement (defined as a decrease of greater than or equal to 2 points from baseline score) was noted at 1 hour in seven patients (24%). By 6 hours 15 patients (52%) had improved, 12 (41%) were unchanged, and two (7%) were worse. Our results suggest that spontaneous, often dramatic improvement occurs in patients with acute ischemic stroke and should be taken into consideration in the design of any trial of acute treatment.
Cerebral vasoreactivity and blood flow before and 3 months after carotid endarterectomy.
Authors: Russell D , Dybevold S , Kjartansson O , Nyberg-Hansen R , Rootwelt K , Wiberg J
Published: June 2011

We measured regional cerebral blood flow and cerebral vasoreactivity before and 3 months after carotid endarterectomy using xenon-133 inhalation with single-photon emission computed tomography and the acetazolamide test in 14 selected patients who had suffered cerebral transient ischemic attacks due to an ipsilateral internal carotid artery stenosis. The patients had neither clinical nor cerebral computed tomographic evidence of infarction. Baseline regional cerebral blood flow was symmetrical before and unchanged after endarterectomy. Before endarterectomy, vasoreactivity in the middle and anterior cerebral artery territories of the symptomatic side was significantly reduced (p less than 0.05); however, vasoreactivity was normalized 3 months after surgery. Our findings strongly suggest that the stenoses caused a reduction in perfusion reserve that was improved by carotid endarterectomy.
Comparison of two-dimensional echocardiography and ultrafast cardiac computed tomography for evaluating intracardiac thrombi in cerebral ischemia.
Authors: Love B B , Struck L K , Stanford W , Biller J , Kerber R , Marcus M
Published: June 2011

Two-dimensional echocardiography has a high specificity for the detection of intracardiac thrombi, but technically difficult studies are often encountered. Ultrafast cardiac computed tomography may be useful in such cases. Using transthoracic two-dimensional echocardiography and ultrafast cardiac computed tomography, we studied 36 patients with cerebral ischemia; one patient had the studies performed on two occasions, making a total of 37 sets of studies. Technical difficulties occurred in 12 echocardiographic (32%) and two ultrafast cardiac computed tomographic (5%) studies. The two techniques agreed in 29 sets of studies (78%). Among the eight discrepant sets of studies, two-dimensional echocardiography was positive for a left ventricular thrombus while ultrafast cardiac computed tomography was negative in three and equivocal in one and echocardiography was equivocal while ultrafast cardiac computed tomography was negative in two and positive in one. In the latter case, a left ventricular thrombus was confirmed at autopsy. In the other discrepant set of studies echocardiography was negative while ultrafast cardiac computed tomography revealed a left atrial and appendage thrombus. Because of its ease of performance and safety, two-dimensional echocardiography is the appropriate initial screening test for left ventricular thrombus. Ultrafast cardiac computed tomography can provide additional information in patients with technically difficult or equivocal two-dimensional echocardiographic studies or patients with cardiac disorders predisposing to atrial thrombi formation.
Histopathologic and morphometric studies of leptomeningeal vessels in moyamoya disease.
Authors: Kono S , Oka K , Sueishi K
Published: June 2011

To clarify the morphogenesis of vascular anastomoses in the leptomeninx, we examined the leptomeningeal vessels of six autopsied patients with moyamoya disease who died of cerebral hemorrhage. Sites examined in the brain (the frontal pole, frontoparietal convexity, and lateral occipital region) were selected by the presence of angiographic abnormalities on the convexity of the hemisphere. At all examined sites, neither the vascular density (number of blood vessels per unit length of underlying cortical surface) nor the arterial/venous ratio differed significantly between the patients and 14 controls. All patients showed dilatative changes of both arteries and veins; however, attenuation or disruption of the internal elastic lamina and fibrous intimal thickening were more prominent in those patients who had had moyamoya disease longer. Our results indicate that the leptomeningeal vessels of moyamoya disease are not newly formed but are merely dilated preexisting vessels and that the structural alteration of the vascular walls suggests their adaptability for participation in the collateral circulation at the cerebral surface.
A review of stroke rehabilitation and physiotherapy.
Authors: Ernst E
Published: June 2011

Most of the members of the therapeutic team in stroke rehabilitation take the effectiveness of physical treatments after stroke for granted. Yet, published data show that the evidence is not so straightforward or easy to evaluate. The majority of the hard evidence, however, does imply that stroke patients benefit from rehabilitation with physiotherapy. This benefit may be statistically small, but for a given individual, it could mean the difference between living at home or in an institution. Few studies address the question of the optimal physiotherapy in stroke rehabilitation. The evidence available today suggests that it does not matter which form of treatment is chosen and that any of the available approaches will improve the patient's functional status. In other words, if an optimal treatment exists, we have, so far, failed to identify it. Until further evidence emerges, we should therefore select therapies that are most cost-effective and that can be given to the largest number of patients. Well-planned clinical trials aimed at finding the best approach and discriminating potential responders from nonresponders are urgently needed.
Role of carotid stenosis in ischemic stroke.
Authors: Zhu C Z , Norris J W
Published: June 2011

Using Doppler ultrasonography, we evaluated the frequency and severity of carotid artery stenosis in 261 patients with carotid ischemic strokes, 813 patients with carotid transient ischemic attacks, 500 patients with asymptomatic neck bruits, and 500 controls. Most patients with strokes and transient ischemic attacks had no associated carotid artery disease (55% and 64%, respectively), and such patients without neck bruits were even more likely to be without carotid artery disease (69% and 77%, respectively). Carotid stenosis was more frequent and more likely to be severe in symptomatic than in asymptomatic patients (p less than 0.0002), even after adjusting for age and sex. Carotid stenosis is present in only a minority of patients with strokes and transient ischemic attacks, especially if neck bruits are absent, and the cause of the ischemic cerebral events in most of these patients remains unexplained.
Clinical features of proven basilar artery occlusion.
Authors: Ferbert A , Brückmann H , Drummen R
Published: June 2011

Our study describes the early symptoms and signs of 85 patients with either basilar artery occlusion or bilateral distal vertebral artery occlusion documented by selective angiography. The most common prodromal symptoms were vertigo, nausea, and headache, which occurred during the 2 weeks before the stroke. Angiographic findings of 49 patients were classified into proximal, middle, and distal basilar artery occlusions. Twenty-two of these patients had additional vertebral artery lesions. A fourth group was composed of 36 patients with bilateral distal vertebral artery occlusion without opacification of the basilar artery through a vertebral artery injection. Onset was sudden in 20 patients; sudden, but preceded by prodromal symptoms in 11 patients; and progressive in 54 patients. Patients with progressive strokes often had bilateral vertebral artery occlusions. Most patients with acute onset had occlusion of the middle and distal basilar artery. An embolic origin of basilar artery occlusion from an arteriosclerotic vertebral artery lesion was assumed to be an important mechanism. An embolus reaching the basilar artery may not necessarily reach the top of the artery, but may also become lodged more proximally.
Assessment of median nerve somatosensory evoked potentials in cerebral ischemia.
Authors: Gott P S , Karnaze D S , Fisher M
Published: June 2011

Seventy patients with cerebral ischemia (21 with transient ischemic attack and 49 with stroke) were studied with short-latency median nerve somatosensory evoked potentials to characterize the evoked potentials in all ischemic patients and to investigate their efficacy for prognosis in stroke. Within 72 hours of symptom onset, all 70 patients received a scaled neurologic function score, with a maximum of 50 points. Somatosensory evoked potential abnormalities were found in 10% (2/19), 42% (15/36), and 93% (14/15) of all patients with initial neurologic examinations who had normal (50 points), mild-moderate (30-49 points), and severe deficits (less than or equal to 29 points), respectively. Thirty-seven of the 49 stroke patients were available for a follow-up neurologic assessment. Eight-nine percent (8/9) of the stroke patients with poor outcome had somatosensory evoked potential abnormalities; 82% (9/11) of the stroke patients with severe neurologic deficits at onset had poor outcome. Results demonstrate that somatosensory evoked potential abnormalities are common in patients with cerebral ischemia but that somatosensory evoked potential findings are not significantly better than a detailed neurologic examination in predicting outcome from stroke.
Slowdown in the decline of stroke mortality in the United States, 1978-1986.
Authors: Cooper R , Sempos C , Hsieh S C , Kovar M G
Published: June 2011

The gradual decline in stroke mortality rates observed in the United States since 1900 accelerated markedly around 1973 for whites and around 1968 for blacks. During the next decade stroke mortality rates decreased by almost 50% so that the United States now experiences one of the lowest stroke mortality rates in the world. Beginning in 1979, however the annual rate of decline in stroke mortality began to slow considerably. Comparing the period 1979-1986 with the previous decade, a 57% slowing in the absolute rate of decline (as estimated by the slope of the linear portion of the mortality curve) was observed for white men; the corresponding slowdowns in the rate of decline were 58% for white women, 44% for black men, and 62% for black women. If the decline during the 1980s had continued at the rate observed for the period 1968/73-1978, there would have been 131,000 fewer stroke deaths during the period 1979-1986, 28,000 fewer in 1986 alone. This slowdown in the rate of decline in stroke mortality is occurring while mortality rates for both coronary heart disease and all causes are leveling off. The reasons for this change in the mortality trend remain unknown, and corresponding trends in the treatment and control of hypertension do not provide an entirely satisfactory explanation.
Effects of nitrous oxide on global and regional cortical blood flow.
Authors: Deutsch G , Samra S K
Published: June 2011

We conducted regional cortical blood flow studies using the xenon-133 clearance technique on 12 volunteers during the administration of 25% and 50% N2O and during baseline conditions (breathing room air or 100% O2). Global cortical blood flow was very highly significantly increased above baseline measures in all subjects by 50% N2O (mean increase 37% above 100% O2 condition). A smaller but still significant increase was observed with 25% N2O. Analysis of regional cortical blood flow revealed heterogeneity in the pattern of changes; that is, the baseline pattern was altered by the inhalation of N2O, most often resulting in an accentuation of relative frontal blood flow. The anterior-posterior gradient in N2O-induced blood flow changes differs from that observed with simple vasodilatory agents, such as CO2, with which the increase is purely systemic and the baseline pattern is preserved. This indicates that N2O has differential effects on cerebral metabolism that may well reflect the typical alterations in experiential state reported by subjects.
Liposome-entrapped superoxide dismutase reduces cerebral infarction in cerebral ischemia in rats.
Authors: Imaizumi S , Woolworth V , Fishman R A , Chan P H
Published: June 2011

We studied the role of superoxide radicals in the pathogenesis of ischemic brain injury using a model of focal cerebral ischemia in 102 rats and liposome-entrapped CuZn-superoxide dismutase, which can penetrate the blood-brain barrier and cell membranes efficiently. The bolus intravenous administration of 25,000 units of liposome-entrapped CuZn-superoxide dismutase elevated superoxide dismutase activities in the blood and brain 1, 2, 8, and 24 hours later as well as in the ischemic hemisphere and contralateral cortex. Determined 24 hours after right middle cerebral and bilateral common carotid artery occlusion by the lack of staining for mitochondrial dehydrogenase activity with 2,3,5-triphenyltetrazolium chloride, infarct sizes were reduced by 33%, 25%, and 18% in the anterior, middle, and posterior brain slices, respectively, by treatment with liposome-entrapped CuZn-superoxide dismutase. Our data demonstrate that superoxide radicals are important determinants of infarct size following focal cerebral ischemia and that liposome-entrapped CuZn-superoxide dismutase may have pharmacologic value for the treatment of focal cerebral ischemic injury.
Effects of normothermic versus mild hyperthermic forebrain ischemia in rats.
Authors: Dietrich W D , Busto R , Valdes I , Loor Y
Published: June 2011

We compared the neuropathological consequences of global forebrain ischemia under normothermia versus mild hyperthermia. Twenty-one rats underwent 20 minutes of four-vessel occlusion during which brain temperature was maintained at either 37 degrees C (normothermia, n = 9) or 39 degrees C (hyperthermia, n = 12). Quantitative neuropathological assessment was conducted 1 or 3 days later. At 1 day following the ischemic insult, normothermic rats demonstrated neuronal injury mainly confined to the most dorsolateral striatum. By 3 days, ischemic cells were present throughout the striatum and CA1 hippocampus in normothermic animals. Compared with normothermic rats, intraischemic hyperthermia significantly increased the extent and severity of brain damage at 1 day after the ischemic insult. Areas of severe neuronal necrosis and frank infarction included the cerebral cortex, CA1 hippocampus, striatum, and thalamus. Morphologic damage was also detected in the cerebellum and pars reticulata of the substantia nigra. An overall mortality rate of 83% was demonstrated at 3 days in the hyperthermic ischemic group. We conclude that intraischemic hyperthermia 1) markedly augments ischemic brain damage and mortality compared with normothermia, 2) transforms ischemic cell injury into frank infarction, and 3) accelerates the morphological appearance of ischemic brain injury in regions usually demonstrating delayed neuronal necrosis. These observations on mild hyperthermia may have important implications for patients undergoing cardiac or cerebrovascular surgery as well as patients following cardiac arrest or those with stroke-in-evolution.
Increasing doses of intracarotid air and cerebral blood flow in rabbits.
Authors: Helps S C , Meyer-Witting M , Reilly P L , Gorman D F
Published: June 2011

We studied the natural history of brain air embolism by observing bubbles in the pial vessels of rabbits and the effect of different doses of intracarotid air on brain function and blood flow. We identified and then studied two doses of air; 25 microliters in five rabbits caused rapid bubble transit, recovery, and then deterioration in brain function and blood flow and 400 microliters in five rabbits caused temporary bubble trapping and sustained deterioration in brain function. These dose responses correlate well with the natural history of divers with air embolism of the brain. All doses of air caused both arteriolar dilatation and reduced blood flow, which were independent of dose, whereas the detrimental effect of air embolism of brain function was dose dependent. Our results suggest that this is a good model of brain air embolism.
Sequential cerebral blood flow changes in short-term cerebral ischemia in gerbils.
Authors: Kato H , Araki T , Kogure K , Murakami M , Uemura K
Published: June 2011

Using quantitative autoradiography, we studied sequential changes in regional cerebral blood flow during and after 2 minutes of bilateral common carotid artery occlusions in 18 gerbils. Occlusion (n = 4) led to severe ischemia in the forebrain (regional cerebral blood flow less than 5% of control [n = 4]) and midbrain (regional cerebral blood flow less than 10% of control), but was morphologically nonlethal. Reperfusion of the brain was complete, and regional cerebral blood flow was not different from control 1 minute after ischemia (n = 4), but hypoperfusion (regional cerebral blood flow 30-50% of control) occurred at 5 minutes (n = 3) and was pronounced at 1 hour (n = 4); at this stage blood flow was inhomogeneous. Hypoperfusion had disappeared at 4 hours (n = 3). Our results indicate that the well-documented sequence of cerebral blood flow changes (i.e., ischemia, initial recovery of blood flow, and delayed hypoperfusion) takes place even after nonlethal cerebral ischemia.
Nimodipine posttreatment does not increase blood flow in rats with focal cortical ischemia.
Authors: Dirnagl U , Jacewicz M , Pulsinelli W
Published: June 2011

We used laser-Doppler flowmetry to study the effect of nimodipine administered after the onset of focal cortical ischemia on regional cerebral blood flow in 16 halothane-anesthetized, mechanically ventilated Wistar rats. We selected the Wistar rats strain since it would provide a wide range of ischemia severities to test the vascular response to nimodipine. Laser-Doppler probes continuously recorded regional cerebral blood flow at two or three sites over the parietal cortex (dura intact) while brain temperature was regulated at 37 degrees C. Occlusion of the right middle cerebral and common carotid arteries reduced cerebral blood flow to a mean of 38% (range 13-77%) of baseline. Thirty minutes later, either 2 micrograms/kg/min nimodipine (n = 8) or its vehicle, polyethylene glycol 400 (n = 8), was administered by a continuous intravenous infusion. Over 60 minutes of treatment, both the nimodipine-treated and vehicle-treated groups showed a trivial (3%) mean increase in cerebral blood flow. Nimodipine failed to augment cerebral blood flow regardless of whether the cortex was severely, moderately, or mildly ischemic.
Activation of coagulation in acute cardioembolic stroke.
Authors: Takano K , Yamaguchi T , Kato H , Omae T
Published: June 2011

The hematologic disorders in patients with acute cardioembolic stroke are not fully understood, and no reliable measures are available to identify patients at high risk for recurrent embolism. We analyzed coagulation and fibrinolytic functions in 22 patients with cardiogenic cerebral embolism less than or equal to 24 hours after onset and in 25 age-matched controls. The levels of antithrombin III, protein C, and alpha 2-plasmin inhibitor were significantly lower in the patients than in the controls (p less than 0.001, 0.02, and 0.05, respectively). In contrast, the plasma concentrations of thrombin-antithrombin III complex and crosslinked D-dimer were markedly higher in the patients than in the controls (p less than 0.01 and 0.001, respectively). At the time of admission, the plasma concentrations of thrombin-antithrombin III complex and crosslinked D-dimer in the eight patients at high risk for recurrent embolization (one with prodromal embolism, three with intracardiac thrombi, and four with recurrent embolization) were 2.8 and 3.5 times, respectively, higher than those in the 14 patients without recurrence or thrombus formation. The lowest concentration of crosslinked D-dimer in the eight patients at high risk for recurrent embolization was 600 ng/ml on admission. Our results suggest that patients with acute cardioembolic stroke have various degrees of consumption coagulopathy and that the plasma concentrations of thrombin-antithrombin III complex and crosslinked D-dimer can be useful indicators of those who are prone to recurrent embolization during this stage.
Platelet volume, aggregation, and adenosine triphosphate release in cerebral thrombosis.
Authors: Tohgi H , Suzuki H , Tamura K , Kimura B
Published: June 2011

We compared whole blood platelet aggregation, adenosine triphosphate release, platelet count, platelet crit (percentage volume of platelets), and mean platelet volume during the acute, subacute, and chronic periods of cerebral thrombosis in 22 patients with value in 29 controls. During the acute and subacute periods, platelet aggregation, platelet count, platelet crit, and mean platelet volume were significantly less in the patients than in the controls (p less than 0.05-0.01) while the adenosine triphosphate release rate per volume of platelets was significantly greater (p less than 0.05). During the acute period, infarct size showed a significant positive correlation with platelet aggregation (r = 0.59, p less than 0.01) and adenosine triphosphate release rate (r = 0.70, p less than 0.001) but a negative correlation with platelet count (r = -0.44, p less than 0.05). Our results suggest that platelet aggregation is reduced during the acute period due to the consumption of platelets during thrombogenesis but that the remaining individual platelets are hyperactive. Platelet consumption during the acute period increases with infarct size. During the chronic period, platelet crit and mean platelet volume were significantly less in the patients than in the controls (p less than 0.01) while the adenosine triphosphate release rate was significantly greater (p less than 0.01), suggesting sustained platelet consumption and chronically enhanced secretion of individual platelets.
The role of neutrophils and platelets in a rabbit model of thromboembolic stroke.
Authors: Bednar M M , Raymond S , McAuliffe T , Lodge P A , Gross C E
Published: June 2011

Cerebral ischemia is accompanied by many of the cardinal features of acute inflammation such as neutrophil and platelet activation and accumulation. We sought to determine whether circulating neutrophils or platelets contribute to brain injury in a rabbit model of thromboembolic stroke that includes a fixed duration of superimposed systemic hypotension. We randomized 18 rabbits to receive either antineutrophil antiserum (n = 6), antiplatelet antiserum (n = 5), or nonimmune serum (n = 7). We assessed brain ischemia by measuring cerebral blood flow, intracranial pressure, and infarct size. Following the intracarotid administration of an autologous clot, cerebral blood flow in all groups fell to less than 5 ml/100 g/min during induced hypotension. After restoration of baseline blood pressure, mean cerebral blood flow in neutropenic animals recovered to 20-30 ml/100 g/min while that in control and thrombocytopenic rabbits remained at less than 10 ml/100 g/min. Intracranial pressure in control animals rose steadily to a final value of 241% of baseline, while a much smaller increase (148% of baseline) was noted in the thrombocytopenic group; no change from baseline was evident in the neutropenic group. Infarct size was significantly (p less than 0.05) reduced in the neutropenic group but not in the thrombocytopenic group. These results suggest that neutrophils may be important contributors to ischemia-induced brain injury whereas the role of platelets is more subtle.
Attenuated neuropathology by nilvadipine after middle cerebral artery occlusion in rats.
Authors: Kawamura S , Shirasawa M , Fukasawa H , Yasui N
Published: June 2011

We investigated the effects of nilvadipine, a calcium antagonist, on cerebral ischemia in rats. Under halothane anesthesia, 30 rats had a 3-0 nylon suture introduced through the extracranial internal carotid artery to occlude the left middle cerebral artery. Nilvadipine was dissolved in polyethylene glycol 400. Immediately following occlusion, group 1 rats (n = 10) were treated subcutaneously with vehicle and group 2 and 3 rats were treated with 1.0 (n = 10) and 3.2 (n = 10) mg/kg nilvadipine, respectively. Perfusion fixation was performed 24 hours later, and the histopathologic outcomes were quantified. In group 1 infarct volume was 28.2 +/- 11.4% of the total cerebral volume; in groups 2 and 3 infarct volumes were 25.5 +/- 11.6% (NS) and 13.9 +/- 9.2% (p less than 0.05 different from group 1), respectively. Nilvadipine decreased ischemic neuronal injury in a dose-dependent manner and may be of use in the treatment of cerebral ischemia.
Hypertension, cigarette smoking, and the decline in stroke incidence in eastern Finland.
Authors: Tuomilehto J , Bonita R , Stewart A , Nissinen A , Salonen J T
Published: June 2011

Finland has high rates of both cardiovascular disease and cardiovascular disease risk factors. We studied random samples of the population 30-59 years of age for risk factors in two provinces of eastern Finland in 1972 and 1977. We then followed both cohorts until 1985 through linkage with national hospital discharge and death certificate registers. The prevalence of hypertension and smoking in both provinces declined between 1972 and 1977, as did the stroke incidence in the 8-year period of follow-up of each cohort. We observed no differences in stroke incidence between the two provinces. The relative risk of stroke in the later period (1977-1985) was 0.71 and 0.58 for men and women, respectively, when compared with the earlier period (1972-1980). Overall, 28% of all stroke events could be attributed to hypertension, 17% to smoking, and 43% to these two factors jointly. The decrease in the prevalence of hypertension and smoking accounted for about 29% of the decline.
A novel treatment for ischemic intracranial hypertension in cats.
Authors: Bell R D , Frazer G D , Osterholm J L , Duckett S W
Published: June 2011

There is no accepted efficacious treatment for ischemic cerebral edema. We show in a cat model of focal cerebral ischemia that infarct volume can be reduced (p less than 0.05) by ventriculocisternal perfusion with an oxygenated fluorochemical emulsion (bis-perfluorobutylethylene). An accompanying effect of such ventriculocisternal perfusion is a reduction in intracranial pressure. At 18 hours following the start of the perfusion, there was a significant (p less than 0.05) difference in intracranial pressure between nonperfused controls (mean 11.4 [range 2.3-23.0] torr, n = 6) and cats perfused with an oxygenated nutrient solution not containing fluorochemical (mean 11.3 [range 3.0-29.0] torr, n = 8) or animals perfused with the oxygenated fluorochemical emulsion (mean 2.21 [range 0-3.5] torr, n = 7). Perfusion with this oxygenated fluorochemical emulsion warrants further study as a treatment for elevated intracranial pressure.
Effect of indomethacin on edema following single and repetitive cerebral ischemia in the gerbil.
Authors: Deluga K S , Plötz F B , Betz A L
Published: June 2011

Repetitive periods of cerebral ischemia result in more severe injury than a single period of ischemia of similar total duration. We investigated the possibility of prostaglandin mediation of this increased injury by attempting to modify brain edema formation with indomethacin pretreatment.

Under halothane/N2O anesthesia, groups of gerbils underwent bilateral carotid occlusion to induce forebrain ischemia. Group I underwent a single 15-minute period of carotid occlusion. Group II underwent three 5-minute periods of occlusion at hourly intervals. Groups III and IV were similar to groups I and II, respectively, but received 0.2 mg/kg indomethacin before carotid occlusion. Cortical and cerebellar water and sodium contents were determined in control animals (n = 6) at time zero and in experimental animals 24, 48, and 72 hours after ischemia (n = 6-10 gerbils/group at each time point).

Cortical water and sodium contents in group II peaked 48 hours after insult (82.15 +/- 0.31% and 420 +/- 14 meq/kg dry wt, respectively) and were significantly higher than control and group I values at both 24 and 48 hours. Cortical water did not change from control in group I animals. Indomethacin pretreatment significantly attenuated increases in water and sodium content seen at 48 hours in gerbils undergoing repetitive ischemia (peak 80.02 +/- 0.45% and 300 +/- 39 meq/kg dry wt), but did not affect mortality.

Indomethacin lessens edema after repetitive cerebral ischemia, suggesting that elevations of cyclooxygenase products are responsible, at least in part, for severe brain edema following repetitive ischemia.
Protective effect of flunarizine on blood-brain barrier permeability alterations in acutely hypertensive rats.
Authors: Nag S
Published: June 2011

Increased cerebrovascular permeability to protein is a well-documented finding in acute and chronic hypertension. In this study, we examined the effect of pretreatment with a calcium entry blocker, flunarizine, on the increased cerebrovascular permeability to protein that develops in norepinephrine-induced acute hypertension.

Protein transfer was assessed qualitatively with Evans blue dye and quantitatively with iodine-125-labeled serum albumin.

Brains of hypertensive rats showed increased permeability to both tracers. The number and size of the areas of Evans blue extravasation were smaller in the hypertensive groups pretreated with flunarizine intravenously. This was supported by the quantitative studies, which demonstrated a significant decrease in protein transfer in total brain of hypertensive rats pretreated with intravenous flunarizine, 1 mg/kg (p less than 0.005) and 2.5 mg/kg (p less than 0.001). Data from individual brain regions showed that pretreatment with flunarizine resulted in significant reduction of protein transfer in most brain regions.

These data support the hypothesis that calcium plays a role in increased cerebral endothelial permeability in hypertension.
Cholinergic deafferentation after focal cerebral infarct in rats.
Authors: Kataoka K , Hayakawa T , Kuroda R , Yuguchi T , Yamada K
Published: June 2011

For a better understanding of neuronal network disturbances after stroke, we investigated the changes in the cholinergic system after experimental focal infarct.

We quantitatively evaluated the highly sensitive acetylcholinesterase histochemistry and local glucose utilization 7 days after left middle cerebral artery occlusion in Wistar rats.

In all rats with occlusion, the ipsilateral frontal cortex and the nucleus basalis Meynert developed no infarct, whereas the subcortical striatum did. In the frontal cortex on the occlusion side, the acetylcholinesterase-positive fiber density was significantly (p less than 0.05) reduced; a computer-assisted image-analyzing system quantified approximately 1.0 m/mm3 brain cortex acetylcholinesterase-positive fibers in the ipsilateral frontal cortex layers II-IV and approximately 9.7 m/mm3 brain cortex acetylcholinesterase-positive fibers in the contralateral frontal cortex layers II-IV. Local glucose utilization was also significantly (p less than 0.05) decreased in the ipsilateral frontal cortex compared to the contralateral side and sham-operated animals.

These results suggest that functional disturbances and disruption of the cholinergic pathway between the frontal cortex and the nucleus basalis Meynert occur after middle cerebral artery occlusion in rats.
Cerebellar glutamine synthetase in children after hypoxia or ischemia.
Authors: Dao D N , Ahdab-Barmada M , Schor N F
Published: June 2011

Glutamate has been implicated in the pathophysiology of acute hypoxic-ischemic encephalopathy. Glutamine synthetase is an enzyme found in astrocytes that converts glutamate to its nontoxic analogue, glutamine. The present study tests the hypothesis that brain glutamine synthetase activity increases in response to acute hypoxic-ischemic insults and not in response to chronic hypoxia-ischemia or non-hypoxic-ischemic neurological disease.

Frozen sections of cerebellum from children who died with acute or chronic hypoxic-ischemic insults or chronic non-hypoxic-ischemic neurological disease were spectrophotometrically assayed for glutamine synthetase activity by an observer who was blinded to the clinical group assignment of each specimen. Enzyme activity was elevated in specimens from children with acute hypoxic-ischemic insults (mean 6.5; range 5.4-7.2 units/g wet tissue wt) as compared with those from patients with chronic hypoxia-ischemia (mean 2.8; range 0.7-10.2 units/g wet tissue wt) or with non-hypoxic-ischemic neurological disease (mean 2.6; range 1.3-3.9 units/g wet tissue wt). This difference was not due to differences in the degree of histological astrocytosis or edema among the specimens. Statistical analysis by the Kruskal-Wallis one-way analysis of variance by ranks test indicates that the three data groups do not come from one population (p less than 0.05).

These results support the notion that glutamine synthetase activity increases in response to acute hypoxic-ischemic nervous system injury in children and that other compensatory mechanisms prevail in the case of chronic hypoxic-ischemic insults.
Cerebrovascular effects of angiotensin converting enzyme inhibition involve large artery dilatation in rats.
Authors: Postiglione A , Bobkiewicz T , Vinholdt-Pedersen E , Lassen N A , Paulson O B , Barry D I
Published: June 2011

The aim of the study was to selectively examine the effects of converting enzyme inhibition on the large brain arteries by using concomitant inhibition of carbonic anhydrase to cause severe dilatation of mainly parenchymal resistance vessels.

Cerebral blood flow was measured using the xenon-133 injection technique in three groups of Wistar rats either during carbonic anhydrase inhibition with acetazolamide (treatment A, n = 8), during carbonic anhydrase inhibition followed by converting enzyme inhibition with captopril 40 minutes later (treatment B, n = 10), or during carbonic anhydrase inhibition preceded by converting enzyme inhibition 20 minutes earlier (treatment C, n = 7).

After treatment A, cerebral blood flow rose rapidly and stabilized within 20 minutes at an average of 220 ml/100 g.min; flow remained stable until at least 60 minutes. After treatment B, cerebral blood flow increased by a further 17.4%, from an average of 219 ml/100 g.min to an average of 257 ml/100 g.min (p less than 0.01). After treatment C, cerebral blood flow stabilized at an average of 238 ml/100 g.min, with flow from 20 to 60 minutes always being higher (from 5% to 17%) than during carbonic anhydrase inhibition alone (p less than 0.02). Thus the additional inhibition of converting enzyme resulted in higher cerebral blood flow than during inhibition of carbonic anhydrase alone.

These results suggest that converting enzyme inhibition reduced resistance of large brain arteries and support the hypothesis that there is some angiotensin II-induced tone in large cerebral arteries.
Incidence of silent lacunar lesion in normal adults and its relation to cerebral blood flow and risk factors.
Authors: Kobayashi S , Okada K , Yamashita K
Published: June 2011

There are few reports comparing incidence of silent lacunar lesions detected by magnetic resonance imaging and cerebral blood flow in neurologically normal adults.

We studied the incidence of such lesions and its relation to cerebral blood flow and risk factors in 246 neurologically normal adults (145 men, mean age 62 years; 101 women, mean age 60 years) who received health screening examinations of the brain.

Thirty-two subjects (13%) had possible silent lacunar lesions (66% of these were recognized by both T1- and T2-weighted image). The regional cerebral blood flow measured by the xenon-133 inhalation method was significantly lower in subjects with silent lacunes than in those without (p less than 0.02). Cerebral blood flow was mildly but significantly decreased in those with silent lacunes (p less than 0.05). Periventricular hyperintensity was closely related to silent lacune (p less than 0.01). However, there was no significant difference in cerebral blood flow between subjects with and without apparent periventricular hyperintensity.

Silent lacunar lesion was closely related to decrease of cerebral circulation and may be an important risk factor for symptomatic cerebrovascular disease.
Evaluation of 2,3,5-triphenyltetrazolium chloride staining to delineate rat brain infarcts.
Authors: Isayama K , Pitts L H , Nishimura M C
Published: June 2011

Accurate and reproducible determination of the size and location of cerebral infarcts is critical for the evaluation of experimental focal cerebral ischemia. The purpose of this study was to compare intracardiac perfusion of 2,3,5-triphenyltetrazolium chloride with immersion of brain tissue in 2,3,5-triphenyltetrazolium chloride to delineate brain infarcts in rats.

After 6, 24, or 48 hours of ischemia induced by permanent middle cerebral artery occlusion, some rats were perfused with 2,3,5-triphenyltetrazolium chloride; other rats were given an overdose of barbiturates, after which brain sections were immersed in 2,3,5-triphenyltetrazolium chloride. Coronal sections were taken 4, 6, and 8 mm from the frontal pole, and infarct areas in perfused and immersed sections were compared; subsequently, the same sections were stained with hematoxylin and eosin.

In rats subjected to 24 or 48 hours of occlusion, areas of infarction were clearly defined with both 2,3,5-triphenyltetrazolium chloride staining techniques, and the infarct sizes correlated well with the results of hematoxylin and eosin staining (r = 0.85-0.94).

These results demonstrate that intracardiac perfusion of 2,3,5-triphenyltetrazolium chloride is an accurate, inexpensive, and efficient staining method to detect infarcted tissue 24 and 48 hours after the onset of ischemia in rats.