bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonpeptide endothelin antagonist. Cerebrovascular characterization and effects on delayed cerebral vasospasm.
Authors: Willette R N , Zhang H , Mitchell M P , Sauermelch C F , Ohlstein E H , Sulpizio A C 
Published: June 2011

(+/-)-SB 209670, a potent nonpeptide endothelin (ET) receptor antagonist, was used to investigate the potential role of ET in cerebral vasospasm associated with subarachnoid hemorrhage.
The effects of (+/-)-SB 209670 were evaluated in isolated segments of canine posterior cerebral arteries in vitro, vascular smooth muscle cells in culture, and in the canine two-hemorrhage model of delayed cerebral vasospasm in vivo.
In the canine basilar and anterior spinal arteries, (+/-)-SB 209670 caused a dose-related inhibition of contractile responses mediated by ET (KB = 4.6 nmol/L and apparent KB = 2.7 nmol/L, respectively). The effects of (+/-)-SB 209670 were mediated by inhibition of ETA receptors since the ETB selective agonist sarafotoxin 6c did not contract these posterior cerebral vessels. (+/-)-SB 209670 also produced a concentration-dependent inhibition (IC50 = 1 nmol/L) of the mitogenic response induced by ET-1 in vascular smooth muscle cell culture. In the canine model of delayed cerebral vasospasm, animals received intracisternal vehicle (saline) or (+/-)-SB 209670 (360 +/- 10 micrograms/d) via osmotic minipump for 7 days. On day 7, the cross-sectional areas in the (+/-)-SB 209670 group were significantly greater than those in the vehicle group in both the basilar artery (68% versus 27%) and anterior spinal artery (78% versus 38%). No differences in blood pressure or heart rate were noted in the two groups, and the vasospasm in the vehicle group did not differ from that of historic controls in this model.
The results suggest that ET plays a significant role in the development of delayed cerebral vasospasm via an interaction with ETA receptors. Furthermore, ETA receptor antagonists may represent a novel therapeutic approach to the treatment of subarachnoid hemorrhage.
Age-related changes in release of endothelium-derived relaxing factor from the carotid artery.
Authors: Paternò R , Faraci F M , Heistad D D 
Published: June 2011

The goal of this study was to determine whether release of endothelium-derived relaxing factor (EDRF) from carotid artery in response to acetylcholine is altered by aging.
Responses were examined in arteries from Wistar rats 6 to 8 months old (young rats), 24 to 26 months old (old rats), and 30 to 32 months old (very old rats). We used a bioassay technique to measure release of EDRF from the carotid artery (donor vessel) and, in the same experiment, measured the diameter of pressurized donor arteries.
Responses of the donor arteries and the detector vessels (aortas) to sodium nitroprusside were not altered in old (24 to 26 months) and very old (30 to 32 months) rats compared with responses in the young rats. Dilator responses in the carotid artery to acetylcholine tended to be lower in the old rats and were significantly lower in very old rats compared with the young rats. Relaxation of the detector vessel during administration of acetycholine to the donor artery was not significantly different in young, old, and very old rats.
Endothelium-dependent dilatation in carotid arteries of old rats is impaired, but release of EDRF and responsiveness of vascular muscle to nitroprusside are normal. Thus, impairment of endothelium-dependent relaxation in the carotid artery during aging is not due to impaired release of EDRF.
Significance of plaque ulceration in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial.
Authors: Eliasziw M , Streifler J Y , Fox A J , Hachinski V C , Ferguson G G , Barnett H J 
Published: June 2011

The importance of carotid plaque ulceration as a cause of cerebral ischemic symptoms remains uncertain. Moreover, its prominence in symptomatic patients with severe carotid stenosis is unknown.
The association between angiographically defined plaque ulceration and risk of subsequent stroke was assessed using Cox proportional hazards regression in 659 patients with severe (70% to 99%) carotid stenosis from the North American Symptomatic Carotid Endarterectomy Trial.
Treatment assignment (medical versus surgical) and degree of ipsilateral stenosis were identified as having a significant influence on the results. The risk of ipsilateral stroke at 24 months for medically treated patients with ulcerated plaques increased incrementally from 26.3% to 73.2% as the degree of stenosis increased from 75% to 95%. For patients with no ulcer, the risk of stroke remained constant at 21.3% for all degrees of stenosis. The net result yielded relative risks of stroke (ulcer versus no ulcer) ranging from 1.24 (95% confidence interval, 0.61 to 2.52) to 3.43 (95% confidence interval, 1.49 to 7.88). Conversely, for surgically treated patients with antecedent presence of an ulcerated plaque, the risk of stroke increased slightly at the highest degrees of stenosis. Overall, carotid endarterectomy reduced the risk of ipsilateral stroke at 24 months by at least 50%. Similar results were obtained for risk of major ipsilateral stroke and risk of all strokes and death.
The presence of angiographically defined ulceration for medically treated symptomatic patients is associated with an increased risk of stroke. The risk of stroke more than doubles at higher degrees of stenosis. Carotid endarterectomy is beneficial in substantially reducing the risk of stroke, regardless of plaque ulceration and degree of severe carotid stenosis.
Relation of cerebral blood flow to motor and cognitive functions in chronic stroke patients.
Authors: Mori S , Sadoshima S , Ibayashi S , Lino K , Fujishima M 
Published: June 2011

The aim of this study was to examine the levels of cerebral blood flow in relation to motor and cognitive functions in 300 chronic unilateral stroke patients (age, 64 +/- 12 years; mean +/- SD).
Cerebral blood flow was measured by the 133Xe inhalation method, adjusted for age, sex, and PCO2 level. Motor function was scored according to Brunnstrom hemiplegic staging and cognitive function according to the Hasegawa dementia rating scale tested in Japanese.
Asymmetries of blood flow between affected and nonaffected hemispheres increased with lesion size and were highest in 11 embolic strokes (20 +/- 9%) and higher in 80 nonembolic cortical infarctions (11 +/- 11%) and 76 hemorrhages (9 +/- 7%) than in the group of 133 subcortical infarctions (2 +/- 6%) or 16 control subjects (1 +/- 2%). Severity of hemiparesis correlated with decreased cerebral blood flow in the affected hemisphere (P < .01) and increased hemispheric asymmetries of blood flow (P < 001). Cognitive impairments, after adjusting for age, correlated with decreased cerebral blood flow in the nonaffected hemisphere (P < .0001), left hemispheric lesions (P < .0005), and embolic stroke (P < .005) but not with asymmetries of blood flow. Among 67 patients having bilateral reductions of cerebral blood flow, 25 patients with left hemispheric lesions showed more severe cognitive impairments than among 42 patients with right hemispheric lesions (P < .05).
We confirmed that severity of hemiparesis correlated with the degree of asymmetries of cerebral blood flow, reflecting the extent and location of the lesions. Bilateral reductions of cerebral blood flow in patients with left hemispheric lesions may in part contribute to cognitive impairments, indicating reductions of global neuronal activities in the contralateral hemisphere or diffuse cerebrovascular changes. Further studies of cerebral metabolism and follow-up of cerebral circulation are required to reveal the pathophysiology and clinical consequences.
A prospective reevaluation of transient ischemic attacks as a risk factor for death and fatal or nonfatal cardiovascular events.
Authors: Howard G , Evans G W , Crouse J R , Toole J F , Ryu J E , Tegeler C , Frye-Pierson J , Mitchell E , Sanders L 
Published: June 2011

Transient ischemic attack (TIA) is generally considered a risk factor for death and cardiovascular events. This assumption is based on comparisons of the survival of the TIA population with that of the general population. Such comparisons may provide biased estimates of the risk associated with TIA because the general population is usually more healthy than TIA patients.
Using a prospective case-control study design, we report the comparison of a TIA population (n = 280) and a control group (n = 399) with a comparable cardiovascular risk factor burden. Proportional hazards analysis was used to compare survival time and time to fatal or nonfatal stroke and/or myocardial infarction for the two study groups. Comparisons were made without adjustment for risk factors and after adjustment for age, race, sex, and major cardiovascular risk factors.
Before adjustment for age-race-sex or risk factors, TIA proved to be a risk factor for early mortality, stroke, and myocardial infarction (P < .05). Adjustment for age-race-sex disparities between the case and control groups explained much of the differences in mortality, as the hazard ratio was reduced from 2.2 to 1.4. However, adjustment for age-race-sex or age-race-sex and risk factors did not markedly reduce the role of TIA as a risk factor for stroke or myocardial infarction.
Although TIA proved to be a risk factor for stroke or myocardial infarction, it apparently plays a smaller role in the risk of death.
Doppler emboli signals vary according to stroke subtype.
Authors: Grosset D G , Georgiadis D , Abdullah I , Bone I , Lees K R 
Published: June 2011

Doppler ultrasound detection of emboli signals may assist in distinguishing embolic from thrombotic stroke. Selected patient groups have a high incidence of such signals. We have examined consecutive stroke cases to identify the incidence of Doppler emboli in different etiologic subtypes of stroke.
Forty-five patients presenting with first-ever acute carotid territory cerebral ischemia were studied prospectively. Transcranial Doppler examination of both middle cerebral arteries, carotid color duplex ultrasound, and transthoracic or transesophageal echocardiography were completed within 48 hours of deficit onset. Clinical and imaging data were interpreted independent of emboli data, and stroke etiology was classified according to recent multicenter trial criteria.
Middle cerebral artery signals were identified in at least one cerebral hemisphere in 41 of the 45 patients. Emboli signals were present in 29 of these 41 cases (71%). These signals were bilateral in 22, within the affected (symptomatic) cerebral hemisphere only in 5, and contralateral only in 2 cases. No emboli signals were detected in any of 8 patients with lacunar stroke. The overall difference in emboli signal counts between etiologic subgroups was significant (P = .001, Kruskal-Wallis). A significantly higher emboli signal count was found within affected cerebral hemispheres than contralaterally in the 8 patients with large artery atherosclerosis (11.3 versus 1 signals per hour, median [95% confidence interval, 3 to 40 and 0 to 3, respectively], P = .02), but this interhemisphere difference was not present for other etiologic subgroups.
Emboli signals are common in patients with acute stroke, with the notable exception of lacunar stroke. This is consistent with the small vessel etiology for the latter group and provides support for the relevance of Doppler emboli signal detection in thromboembolic cerebrovascular disease.
Transcranial color-coded sonography of the basal cerebral circulation. Reference data from 115 volunteers.
Authors: Martin P J , Evans D H , Naylor A R 
Published: June 2011

Transcranial color-coded sonography is a new development in noninvasive cerebral vascular imaging. Reference data using this technique are described.
Blood velocities and pulsatility and resistance indices were determined in the anterior cerebral, middle cerebral, posterior cerebral, vertebral, and basilar arteries in 115 volunteers after correction for the angle of insonation.
Of 1265 basal arterial segments, 1053 were insonated (83%). The vertebral (98%), basilar (92%), middle cerebral (84%), and posterior (P1) cerebral arteries (84%) were the most successfully insonated, with the anterior (73%) and posterior (P2) cerebral arteries (72%) the least successfully insonated. Mean and end-diastolic blood velocities decreased significantly with age in all vessels (middle cerebral artery mean velocity: 20 to 39 years, 74 cm/s [71-76]; > 60 years, 58 cm/s [55-61], P < .0001; mean with 95% confidence intervals), and peak systolic velocity decreased significantly except in the posterior (P2) cerebral artery. Blood velocities were higher in women except in the > 60-year group. Velocities showed the least interhemispheric asymmetry in the middle cerebral artery (r = .85 and r = .83, peak and mean velocities, respectively) and the greatest asymmetry in the posterior (P2) cerebral artery (r = .58 and r = .59, peak and mean velocities, respectively). Pulsatility and resistance indices increased significantly with age in all vessels (middle cerebral artery pulsatility index: 20 to 39 years, 0.84 [0.82-0.87], > 60 years, 0.97 [0.93-1.02], P < .0001; middle cerebral artery resistance index: 20 to 39 years, 0.55 [0.54-0.56], > 60 years, 0.62 [0.60-0.64], P < .0001).
Transcranial color-coded sonography can image the basal cerebral arteries and distinguish vertebral from basilar artery flow and enables pulsed Doppler interrogation with correction for the angle of insonation.
Nitric oxide inhibition aggravates ischemic damage of hippocampal but not of NADPH neurons in gerbils.
Authors: Sancesario G , Iannone M , Morello M , Nisticò G , Bernardi G 
Published: June 2011

Nitric oxide may influence pathophysiology of brain ischemia in a complex way depending on the sources of its production either from neurons or endothelial cells. We investigated whether inhibition of nitric oxide synthesis affects postischemic neuronal death in hippocampus. Moreover, we evaluated whether the presence of nitric oxide synthase activity in specific neurons protects these against ischemia in the hippocampus, striatum, and sensorimotor cortex.
To inhibit nitric oxide synthase, several dosing regimens of NG-nitro-L-arginine methyl ester (L-NAME) were used (5 or 50 mg/kg IP, twice a day for 4 days, or 30 mg/kg IV) in gerbils. Control animals received either the isomer NG-nitro-D-arginine methyl ester or the vehicle. The gerbils underwent 10-minute occlusion of carotid arteries under ether anesthesia and controlled body temperature while physiological parameters were monitored. Neuronal damage was assessed 5 days after ischemia using Nissl-stained sections of hippocampus. Nitric oxide synthase neurons were histochemically stained for reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity.
L-NAME treatments, but not the chronic one at 5 mg/kg, induced elevation of blood pressure (30% to 80% greater than the control level, P < .01), as observed shortly before and after bilateral carotid occlusion. Postischemic neuronal loss in the CA1 through CA4 sectors was worsened by chronic pretreatment with L-NAME at 50 mg/kg (eg, CA1 neuronal counts per 100-microns length: 3.2 +/- 2.74, mean +/- SD; n = 19; P < .01). After the acute (30 mg/kg) or chronic pretreatment at lower dosage (5 mg/kg) with L-NAME, neuronal loss was comparable to that of animals treated with the D-isomer or the vehicle (CA1 counts in vehicle-treated animals: 7.65 +/- 6.51, mean +/- SD; n = 14). None of the L-NAME treatments affected postischemic survival of NADPH diaphorase-positive neurons in hippocampus, striatum, and sensorimotor cortex.
These observations demonstrate that inhibition of endothelial and neuronal nitric oxide synthase activity does not modify resistance of nitric oxide-producing neurons to transient ischemia. The severe inhibition of nitric oxide production aggravates postischemic neuronal death in the hippocampus, whereas the mild inhibition is ineffective.
The effect of ritanserin, a 5-HT2 receptor antagonist, on ischemic cerebral blood flow and infarct volume in rat middle cerebral artery occlusion.
Authors: Takagi K , Ginsberg M D , Globus M Y , Busto R , Dietrich W D 
Published: June 2011

In a previous study from our laboratory, ritanserin, a specific 5-HT2 serotonin receptor antagonist, reduced ischemic damage in the setting of transient global ischemia. In this study, we examined the effect of ritanserin on ischemic cerebral blood flow, systemic blood pressure, and infarct volume in the model of permanent focal ischemia with brain temperature controlled at 35.0 degrees C to 36.0 degrees C.
Thirty-seven male Sprague-Dawley rats were used. The right middle cerebral artery was permanently occluded. Ritanserin (8 mg/kg) or vehicle was continuously administered intravenously for 90 minutes starting 10 minutes after middle cerebral artery occlusion. Cerebral blood flow was monitored by laser Doppler flowmetry in the ischemic cortex before and for 2 hours after arterial occlusion. Brains were perfusion-fixed 3 days later, and infarct volumes were measured.
Mean arterial blood pressure was not affected by treatment. In the vehicle and ritanserin groups, mean ischemic cerebral blood flow (percent of preischemic values) was 34.6 +/- 14.7% (mean +/- SD) and 26.6 +/- 15.0%, respectively. Hemispheric infarct volumes were 119.3 +/- 49.4 mm3 and 136.6 +/- 49.6 mm3, respectively. No significant differences were recognized.
Intravenous administration of ritanserin did not affect mean arterial blood pressure or cerebral blood flow in the ischemic region during the acute phase of ischemia. No protective effect of ritanserin was apparent in the setting of permanent focal ischemia when treatment was begun shortly after the onset of ischemia.
Efficacious experimental stroke treatment with high-dose methylprednisolone.
Authors: de Courten-Myers G M , Kleinholz M , Wagner K R , Xi G , Myers R E 
Published: June 2011

Recent studies reveal success in treating spinal cord trauma with early, high-dose methylprednisolone. As in spinal cord research, failure to find therapeutic effects with steroids in studies of acute stroke treatment may reflect institution of treatment too late and at too low dosage. We presently test the efficacy of stroke treatment with methylprednisolone administered early and at high doses using a cat temporary middle cerebral artery occlusion model.
We occluded the middle cerebral artery for 4 hours in 24 pentobarbital-anesthetized cats. To enhance the probability of brain injury, we maintained the cats' serum glucose concentrations at high levels both during occlusion and for 6 hours afterward. Using a blinded, randomized study design, we treated 12 cats with methylprednisolone (30 mg/kg IV infused over 15 minutes starting 30 minutes after occlusion followed by 5.4 mg.kg-1.h-1 IV for the next 23 hours) and 12 control cats with vehicle. During and for 8 hours after occlusion, we monitored cerebral blood flow, brain and rectal temperatures, and multiple cardiovascular and blood compositional parameters. We assessed brain pathological outcome after animal survival for 4 days or after acute death from hemispheric edema.
Experimental and control animals showed similar early mortality rates (treated, 3/12; controls, 4/12). However, surviving methylprednisolone-treated cats (n = 9) showed a mean infarct size more than six times smaller than in the control animals (n = 8) (mean +/- SEM, 2.4 +/- 0.7% versus 15.6 +/- 6.2% of the ischemic territory, respectively; P < .05). The methylprednisolone-treated animals also showed less marked reduction in cerebral blood flow during ischemia than did the controls (mean +/- SEM, 58 +/- 5% versus 74 +/- 4%; P < .005).
Administering methylprednisolone at high doses early after onset of ischemia significantly reduces tissue injury in cats that survive 4 days of temporary middle cerebral artery occlusion. This improvement in outcome occurs in the setting of significant increases in ischemic cerebral blood flow. However, methylprednisolone treatment did not reduce hemispheric edema in animals that died early after temporary middle cerebral artery occlusion.
Cerebral ischemic attack caused by postprandial hypotension.
Authors: Kamata T , Yokota T , Furukawa T , Tsukagoshi H 
Published: June 2011

Food ingestion sometimes induces systemic hypotension (postprandial hypotension). Although the possibility of stroke occurring postprandially has been suggested, no cases have been reported until now.
A 78-year-old man experienced repeated transient ischemic attacks after almost every ingestion of food and showed orthostatic and postprandial hypotension. An angiogram revealed occlusion of his left carotid artery and stenosis of his right middle cerebral artery.
Postprandial as well as orthostatic hypotension can be a risk factor for stroke in patients with severe occlusive cerebrovascular disease.
Reduction of functional neuronal connectivity in long-term treated hypertension.
Authors: Mentis M J , Salerno J , Horwitz B , Grady C , Schapiro M B , Murphy D G , Rapoport S I 
Published: June 2011

Anatomic imaging of patients with chronic well-treated hypertension has demonstrated dilatation of the lateral cerebral ventricles and left brain atrophy, whereas positron emission tomography has shown only subtle reductions in regional cerebral metabolic rates for glucose in some subcortical nuclei. To further explore the implications of the imaging changes, an analytic technique designed to determine functional neuronal connectivity between regions of interest (ROIs) was applied to the data on regional cerebral metabolic rates for glucose to determine if and where in the brain reduction of functional neuronal connectivity occurred.
Glucose metabolism was measured by positron emission tomography in 17 older men (age, 68 +/- 8 years) with well-controlled, noncomplicated hypertension of at least 10 years' duration and in 25 age- and sex-matched healthy control subjects. A significant correlation difference analysis was performed to determine which ROI pairs had reduced correlation coefficients (reduced functional neuronal connectivity). The vascular pattern of the reduction was determined after allocating the ROIs to their appropriate vascular territories.
Compared with the control subjects, hypertensive patients had reduced correlation coefficients in cortical territories of the internal carotid arteries but not of the vertebrobasilar arteries. The border zone supplied by the middle and anterior cerebral arteries was most affected.
The border zone between the anterior and middle cerebral arteries is vulnerable to ischemia from carotid pathology, systemic hypotension, or both. We hypothesize that although these hypertensive patients were "well controlled" and had normal neuropsychological tests, they may have experienced ischemia severe enough to cause border zone reduction of functional neuronal connectivity as a result of carotid pathology, antihypertensive medications, hypotensive episodes with a right-shifted autoregulation curve, or other factors in isolation or combination.