bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific changes in human brain following reperfusion after cardiac arrest.
Authors: Fujioka M , Okuchi K , Sakaki T , Hiramatsu K , Miyamoto S , Iwasaki S
Published: June 2011

Very few reports are available on serial changes in human brain after cardiac arrest. The primary objective of this study is to investigate sequential neuroradiological changes in patients remaining in a persistent vegetative state following resuscitation after cardiac arrest.

We repeatedly studied eight vegetative patients resuscitated from unexpected out-of-hospital cardiac arrest using computed tomographic (CT) scanning and high-field magnetic resonance (MR) imaging at 1.5 T.

In seven of the eight patients, CT scans obtained between days 2 and 6 features symmetrical low-density lesions in the bilateral caudate, lenticular, and/or thalamic nuclei. These ischemic lesions were persistently of low density on serial CT scans. In these seven patients, MR images demonstrated what were thought to be hemoglobin degradation products derived from minor hemorrhages localized in the bilateral basal ganglia, thalami, and/or substantia nigra. Diffuse brain edema in the acute stage and diffuse brain atrophy in the chronic stage were consistent neuroradiological findings. No abnormal enhanced lesions were demonstrated by CT scans.

The most characteristic findings on high-field MR images were symmetrical lesions in the bilateral basal ganglia, thalami, and/or substantia nigra with specific changes suggestive of minor hemorrhages that were not evident on CT scans. We speculate that these minor hemorrhages result from diapedesis of red blood cells in these regions during the reperfusion period through the endothelium disrupted by ischemia-reperfusion insult.
An integrated system for multidisciplinary assessments in stroke rehabilitation.
Authors: Kalra L , Fowle A J
Published: June 2011

There is increasing emphasis on the use of integrated systems for timely, accurate, and efficient data collection for a range of service, audit, quality, and research applications. The present study evaluates the acceptability and the quality of data collected on a ward-based system over a 6-month period.

A multidisciplinary system specific for stroke rehabilitation was used. Members of each discipline were required to enter demographic, medical, nursing, therapy, and psychosocial data as appropriate to their specialty. A users' survey was undertaken at the beginning and at the end of the study. The quality and completeness of data entry were assessed by a "snapshot" of the database at the end of the study period. Primary users (n = 13) included physicians, nurses, and therapists.

The user survey at the end of the evaluation showed a significant increase in confidence in using the system. Although the frequency of use had increased, the time spent in data entry had decreased significantly. The increase in work load, estimated at 15 to 60 minutes per week, was considered to be balanced by the benefits in patient care, audit, and research. There were 67 medical and 1046 other assessments on 67 patients entered into the system. Seven patients (11%) had incomplete medical records. Nursing and therapy assessments had been entered for all patients at admission and on discharge, with more than 95% of all possible assessments monitoring recovery being recorded accurately compared with conventional records.

The study showed that it was possible to introduce a computerized multidisciplinary assessment system on rehabilitation wards as a part of day-to-day work without the need for significant extra resources.
The European Stroke Scale.
Authors: Hantson L , De Weerdt W , De Keyser J , Diener H C , Franke C , Palm R , Van Orshoven M , Schoonderwalt H , De Klippel N , Herroelen L
Published: June 2011

For detecting therapeutic effect and matching of treatment groups in stroke trials, a scale that meets the clinimetric criteria is of the utmost importance.

The European Stroke Scale consists of 14 items selected for their specificity and their prognostic value. It is designed for patients with middle cerebral artery stroke. Interrater reliability, internal consistency, and time for completion were investigated in 74 patients. Intrarater reliability was studied in 38 patients. To establish concurrent validity, two trials were performed in 20 and 44 patients. The scale was correlated with the MCA Neurological Scale, the Canadian Stroke Scale, the Scandinavian Stroke Scale, the Barthel Index, and the Rankin Scale. Correlations were calculated by means of Spearman's correlation coefficient. The trial in 44 patients also investigated the prognostic validity of the scale for 1-month and 8-month neurological, functional, and handicap status. These data were analyzed by linear regression.

Interrater (kappa value range, 0.62 to 0.85) and intrarater (kappa value range, 0.65 to 1.00) reliability for each item was good, and internal consistency was excellent (Cronbach's alpha coefficient, 0.92). Mean time for completion was 8.2 minutes (range, 4 to 14 minutes). Correlations of the European Stroke Scale with other neurological scales ranged from 0.93 to 0.95. The correlation with the Barthel Index and the Rankin Scale was 0.84 and -0.86. The R2 values for prognostic validity ranged from 0.45 to 0.81 (P < or = .0001).

The European Stroke Scale has been developed according to the clinimetric criteria.
Graded bioassay for demonstration of brain rescue from experimental acute ischemia in rats.
Authors: Aronowski J , Ostrow P , Samways E , Strong R , Zivin J A , Grotta J C
Published: June 2011

This study explored the correlation between duration of focal ischemia and infarct volume in spontaneously hypertensive rats as a measure of outcome after neuroprotective intervention.

We used 2,3,5-triphenyltetrazolium chloride staining to discriminate infarcted tissue and calculate infarct volume 24 hours after temporary tandem common carotid/middle cerebral artery occlusion lasting 5 to 150 minutes. We used a graded bioassay described by logistic function and executed by computer program (ALLFIT) to evaluate changes in infarct volume after increasing durations of ischemia. The method allowed us to calculate the maximal infarct volume (Volmax) and the duration of ischemia before reperfusion producing half-maximal infarct size (T50). Hypothermia and the N-methyl-D-aspartate antagonist CNS-1102 begun after the onset of ischemia were tested for their ability to reduce Volmax and prolong T50 as analyzed by ALLFIT.

Volmax was 180.6 +/- 22.4 mm3 and T50 was 45.9 +/- 5.8 minutes in control rats. Hypothermia (30 degrees C) applied during ischemia reduced Volmax by 66 mm3 and extended T50 by 50% (P < .05 for each comparison). CNS-1102, like hypothermia, extended T50 by 44% but did not have an effect on Volmax.

Analysis of the changes of infarct size after increasing durations of ischemia indicates that although both were protective, the two treatments tested may exhibit different profiles of efficacy. This method of analyzing ischemia-induced damage may be very sensitive for studying the efficacy and possible clinical use of neuronal protective therapies for hyperacute stroke.
Competitive N-methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats.
Authors: Nishikawa T , Kirsch J R , Koehler R C , Miyabe M , Traystman R J
Published: June 2011

We tested the hypothesis that administration of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist NPC 17742 (2R,4R,5S-[2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid]) during transient focal ischemia affects early postischemic brain injury.

Halothane-anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 4 hours of reperfusion. Control cats received saline (n = 7). Experimental cats were treated with NPC 17742 at a dose of 5 mg/kg IV from 45 minutes of ischemia to 15 minutes of reperfusion and 2.5 mg/kg per hour for 4 hours of reperfusion (NPC-5; n = 7) or 50 mg/kg from 45 minutes of ischemia to 15 minutes of reperfusion and 25 mg/kg per hour for 4 hours of reperfusion (NPC-50; n = 5).

Microsphere-determined blood flow to the ipsilateral inferior temporal cortex and caudate nucleus decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the three groups. Triphenyltetrazolium-determined injury volume of ipsilateral cerebral hemisphere (saline, 24 +/- 8%; NPC-5, 4 +/- 2%; NPC-50, 5 +/- 2% of hemisphere; mean +/- SE) and caudate nucleus (saline, 72 +/- 6%; NPC-5, 37 +/- 10%; NPC-50, 26 +/- 4%) was less in cats treated with both doses of drug compared with cats treated with saline. Recovery of somatosensory evoked potential amplitude was incomplete and similar in all groups (saline, 36 +/- 14%; NPC-5, 58 +/- 8%; NPC-50, 51 +/- 15% of baseline).

These data indicate that activation of NMDA receptors plays an important role in the mechanism of acute injury in both cortex and caudate after 1 hour of transient focal ischemia in the cat. Because NPC 17742 afforded protection when administered at the end of ischemia and during reperfusion, NMDA receptor activation during reperfusion may contribute to the progression of injury in ischemic border regions.
Accuracy of hospital discharge abstracts for identifying stroke.
Authors: Leibson C L , Naessens J M , Brown R D , Whisnant J P
Published: June 2011

Much of the available data on stroke occurrence, service use, and cost of care originated with hospital discharge abstracts. This article uses the unique resources of the Rochester Epidemiology Project to estimate the sensitivity and positive predictive value of hospital discharge abstracts for incident stroke.

The Rochester Stroke Registry was used to identify all confirmed first strokes (hospitalized and nonhospitalized) among Rochester residents for 1970, 1980, 1984, and 1989 (n = 364). The sensitivity of discharge abstracts was estimated by following these individuals for 12 months after stroke to determine the proportion assigned a discharge diagnosis of cerebrovascular disease (International Classification of Diseases [ICD] codes 430 through 438.9). The positive predictive value of discharge abstracts was assessed by identifying all hospitalizations of Rochester residents with an ICD code of 430-438.9 in 1970, 1980, and 1989 (n = 377). Events were categorized as incident stroke, recurrent stroke, stroke sequelae, or nonstroke after review of the complete community-based medical record by a neurologist.

Only 86% (n = 313) of all first-stroke patients in 1970, 1980, 1984, and 1989 were hospitalized. Of hospitalized patients, only 76% were assigned a principal discharge diagnosis code of 430-438.9. Fatal strokes and those occurring during a hospitalization were less likely to be identified. Among all hospitalizations of Rochester residents in 1970, 1980, and 1989, there were 377 with a principal diagnosis code of 430-438.9. Less than half (n = 177) were determined by the neurologist to be incident stroke; only 60% (n = 225) were either incident or recurrent stroke. Comparison of alternative approaches showed the validity of discharge abstracts was enhanced by increasing the number of diagnoses and excluding codes with poor positive predictive value.

This study provides previously unavailable estimates of the sensitivity of stroke-coded hospitalizations for a US community. A model for improving the sensitivity and positive predictive value of discharge abstracts is presented.
Carotid artery and heart disease in subtypes of cerebral infarction.
Authors: Lindgren A , Roijer A , Norrving B , Wallin L , Eskilsson J , Johansson B B
Published: June 2011

The aim of the study was to determine the prevalences of carotid artery disease and major and minor potential cardioembolic sources (1) in patients with cerebral infarction and age-matched control subjects and (2) in different clinical subtypes of cerebral infarction.

A series of 166 consecutive patients with cerebral infarction and 59 control subjects was examined. The study protocol included clinical subtyping of the cerebral infarctions, ultrasonography of the carotid arteries, transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), ECG, and examination of the brain with computed tomography, magnetic resonance imaging, or autopsy.

Carotid artery stenosis > or = 80% or occlusion was present in 35 (21%) patients but in no control subjects (P < .001; chi 2 test). A major potential cardioembolic source was detected in 65 (39%) patients and 3 (5%) control subjects. Atrial fibrillation was present in 35 (21%) patients and 3 (5%) control subjects at initial ECG (P < .01) and in 47 (28%) patients at repeat examination; 17 patients had paroxysmal atrial fibrillation. Sinus rhythm and a major potential cardioembolic source were detected in 18 (11%) patients but in no control subjects (P < .01) at TTE (all patients and control subjects examined) or TEE (118 patients and 52 control subjects examined). The frequency of a minor potential cardioembolic source detectable at TTE or TEE was similar in the patient and control groups (51% and 53%, respectively [NS]) and increased significantly with age. A finding of carotid artery stenosis > or = 80% or occlusion, atrial fibrillation, or a major cardioembolic source detected at TTE or TEE was more frequent among patients with cortical symptoms from anterior or middle cerebral artery territories than among those with lacunar syndromes (66% versus 22%, respectively). The probable source of cerebral infarction was identified in most of the 166 patients: cardiac embolism in 28% of cases (n = 46), carotid artery disease in 8% (n = 14), both cardiac embolism and carotid artery disease in 7% (n = 11), and lacunar infarction in 23% (n = 38). In 57 (34%) of the patients no unequivocal cause of the cerebral infarction was found.

The prevalences of carotid artery and heart disease differ significantly between clinical subtypes of cerebral infarction. The cause of cerebral infarction remains uncertain in one third of patients. Because a minor potential cardioembolic source occurs in about 50% of both patients and control subjects, this finding is of questionable value as a risk factor for stroke in the elderly.
B-mode-detected carotid artery plaque in a general population. Atherosclerosis Risk in Communities (ARIC) Study Investigators.
Authors: Li R , Duncan B B , Metcalf P A , Crouse J R , Sharrett A R , Tyroler H A , Barnes R , Heiss G
Published: June 2011

There is little information on the distribution of atherosclerotic lesions of the extracranial carotid artery wall in free-living populations. The purpose of the present study was to describe the prevalence from 1987 through 1989 of extracranial carotid artery plaque and plaque with acoustic attenuation (shadowing) lesions in a general population of white and black adults from four US communities.

B-mode ultrasound was used to characterize wall lesions in the common and internal carotid arteries and at the carotid artery bifurcation in 14,046 men and women 45 to 64 years old who participated in the Atherosclerosis Risk in Communities Study baseline survey.

Thirty-four percent of participants had plaque and 6.4% had plaque with acoustic shadowing. The prevalence of plaque with acoustic shadowing increased steadily with age from 2.5% at ages 45 to 49 to 12.4% at ages 60 to 64. Overall, whites had more plaque with acoustic shadowing lesions than blacks (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.02 to 1.46), and men had more than women (OR, 1.42; 95% CI, 1.22 to 1.63). However, plaque lesions in the common carotid artery were less common among whites than among blacks, and no racial difference was observed in the prevalence of plaque with acoustic shadowing at this segment.

Although these prevalence rates are likely to be underestimated because of the emphasis on arterial boundary visualization of the scanning protocol, they show a large, mostly asymptomatic burden of atherosclerosis in these populations, especially among older individuals. Site-specific frequency rates of plaque varied between blacks and whites. Among those with plaque, however, whites had more lesions with acoustic shadowing attenuation.
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.
Cerebral vasoreactivity in unilateral carotid artery disease. A comparison of blood flow velocity and regional cerebral blood flow measurements.
Authors: Dahl A , Russell D , Nyberg-Hansen R , Rootwelt K , Bakke S J
Published: June 2011

Hemodynamic information obtained by assessing cerebral vasoreactivity is of clinical interest and may have prognostic significance in patients with occlusive carotid disease. The aim of this study was to compare the results of transcranial Doppler and regional cerebral blood flow studies when used to assess cerebral vasoreactivity.

Blood flow velocities in both middle cerebral arteries and regional cerebral blood flow in their respective perfusion territories were compared in 52 patients with severe unilateral carotid stenosis or occlusion. The studies were first performed under basal conditions and repeated after the intravenous administration of 1 g acetazolamide.

Asymmetry (normal compared with pathological side) in middle cerebral artery blood velocity increase was significantly greater than the asymmetry in cerebral blood flow increase in the perfusion territories of the arteries. A significant correlation (r = .63, P < .0001) was found between asymmetry in percent velocity increase and asymmetry in absolute cerebral blood flow increase. The two methods agreed in their assessment of either a normal or a reduced vasoreactivity in 38 subjects and disagreed in 14. In six of the latter patients, who had no evidence of cerebral infarction, the asymmetry in velocity increase was abnormal, whereas asymmetry in flow increase was assessed as normal.

We found a good correlation between the asymmetry in regional cerebral blood flow increase in the middle cerebral artery perfusion territories and asymmetry in the velocity increase in the middle cerebral arteries after administration of acetazolamide. These results suggest that transcranial Doppler examination combined with the acetazolamide test may be used in clinical situations to assess cerebral vasoreactivity.
A comparison of intra-arterial and intravenous tissue-type plasminogen activator on autologous arterial emboli in the cerebral circulation of rabbits.
Authors: Hamilton M G , Lee J S , Cummings P J , Zabramski J M
Published: June 2011

The efficacy of thrombolytic therapy for treatment of embolic stroke has been a subject of both experimental and clinical examination. The aim of this study was to compare the efficacy, in regard to reduction of volume of ischemic brain, of two different modes of administration (ie, intra-arterial and intravenous) of tissue-type plasminogen activator (TPA) given 30 minutes after experimental embolic stroke in rabbits.

A randomized, blinded, controlled experimental trial was undertaken. Embolic stroke was simulated in rabbits by injecting fragments of autologous arterial thrombus into one internal carotid artery. Thirty minutes after embolization, the rabbits were blindly treated with 2 mg/kg intra-arterial TPA, 2 mg/kg intravenous TPA, or saline (all n = 10). Six hours after embolization the rabbits were killed. The brains were perfused with triphenyltetrazolium chloride and cut into 0.5-cm-thick coronal sections, and the areas of ischemia were measured.

Administration of TPA resulted in a significant reduction in the volume of ischemic cerebral injury (P < .0001): control animals sustained ischemic injury to 20.1 +/- 4.6% (mean +/- SD) of total brain compared with 4.6 +/- 4.1% for animals treated with intra-arterial TPA and 3.4 +/- 2.6% for those treated with intravenous TPA. The difference between intra-arterial and intravenous TPA treatment was not significant (P = .786).

In this rabbit model of embolic stroke, administration of TPA within 30 minutes resulted in a dramatic reduction in the amount of ischemic injury, with equal efficacy for the two modes of administration. These results favor the treatment of acute embolic stroke with intravenous TPA, given the rapidity with which intravenous therapy can be established in the clinical setting.
An experimental model of symptomatic vasospasm induced by oxyhemoglobin in rabbits.
Authors: Otsuji T , Endo S , Hirashima Y , Nishijima M , Takaku A
Published: June 2011

There are many experimental models for studies of cerebral vasospasm. However, no ideal model has been established thus far to comparatively reproduce the ischemic state of the brain that may occur in patients after subarachnoid hemorrhage.

In the present study, we attempted to induce severe vasospasm in rabbits by using an oxyhemoglobin-rich blood product prepared from hemolyzed arterial blood and evaluate neurological symptoms, cerebral angiogram, cerebral blood flow, and histology.

Clinically significant neurological symptoms were observed in about half of the rabbits. There was no significant correlation between angiographic results of the vasospastic state of the main artery and the severity of neurological symptoms observed. However, the cerebral blood flow was significantly lower than in the control group and significantly correlated with the severity of neurological symptoms. On histological examination, lesions were found in about half of the rabbits. Development of obvious infarction was found more frequently than in other reported models.

These results suggest that this model is appropriate as an experimental model of vasospasm occurring after subarachnoid hemorrhage and is especially useful in that it induces vasospasm intense enough to cause obvious infarction.
Neuroprotection with a calpain inhibitor in a model of focal cerebral ischemia.
Authors: Hong S C , Goto Y , Lanzino G , Soleau S , Kassell N F , Lee K S
Published: June 2011

Excessive elevation of intracellular calcium and uncontrolled activation of calcium-sensitive events are believed to play a central role in ischemic neuronal damage. Calcium-activated proteolysis by calpain is a candidate to participate in this form of pathology because it is activated under ischemic conditions and its activation results in the degradation of crucial cytoskeletal and regulatory proteins. The present studies examined the effects of a cell-penetrating inhibitor of calpain on the pathological outcome after transient focal ischemia in the brain.

Twenty-five male Sprague-Dawley rats were divided into four groups: a saline-treated group, a vehicle-treated group, and two calpain inhibitor-treated groups (Cbz-Val-Phe-H; 30-mg/kg and 60-mg/kg cumulative doses). Ischemia was induced by occluding the left middle cerebral artery and both common carotid arteries for 3 hours followed by reperfusion. Animals were killed 72 hours after surgery, and quantitative measurements of infarction volumes were performed using histological techniques. Eight additional rats were killed 30 minutes after ischemia and examined for the extent of proteolysis using immunoblot techniques. A final group of 12 animals was decapitated after injection of vehicle or calpain inhibitor, and the proteolytic response was measured after 60 minutes of total ischemia.

Rats treated with Cbz-Val-Phe-H exhibited significantly smaller volumes of cerebral infarction than saline-treated or vehicle-treated control animals. Intravenous injections of cumulative doses of 30 mg/kg or 60 mg/kg of Cbz-Val-Phe-H were effective in reducing infarction, edema, and calcium-activated proteolysis. The proteolytic response to postdecapitation ischemia was also reduced by the calpain inhibitor.

These results demonstrate the neuroprotective effect of a cell-penetrating calpain inhibitor when administered systemically. The findings suggest that targeting intracellular, calcium-activated mechanisms, such as proteolysis, represents a viable therapeutic strategy for limiting neurological damage after ischemia.
Pilot study of low-molecular-weight heparin in the treatment of acute ischemic stroke.
Authors: Kay R , Wong K S , Woo J
Published: June 2011

Our purpose was to assess the feasibility and risk of performing a double-blind placebo-controlled study of low-molecular-weight heparin in the treatment of acute ischemic stroke.

Fifty-five patients were treated within 48 hours of stroke onset. Pretreatment computed tomography was performed to rule out cerebral hemorrhage. Fraxiparine (6000 IU per day) was given subcutaneously for 7 days. No adverse reaction was encountered during the treatment period. At 3 months, 26 patients were independent, 21 moderately disabled, 4 severely disabled, and 4 dead.

It would be safe and practical to conduct a clinical trial on the use of Fraxiparine in the treatment of acute ischemic stroke.