bluuebunny/crossref_metadata_2025 huggingface dataset:
Depression After Stroke
Authors: Kotila Mervi , Numminen Heikki , Waltimo Olli , Kaste Markku
Published: June 2011

Background and Purpose
—We compared the incidence and severity of depression at 3 and 12 months after stroke in patients and their chief caregivers (spouses, 63%; children, 37%) in four districts of Finland, two with and two without after-hospital-discharge interventional programs (outpatient rehabilitation and activities of the local divisions of the Finnish Heart Association [FHA]). A population-based stroke register was used, and factors influencing depression were analyzed.

Methods
—A stroke register of patients recruited over 2 years in four different districts (total population, 134 804) in Finland; 594 first-ever strokes were registered. Beck’s Depression Inventory (BDI), with 10 as the cutoff point for depression, was applied to 321 of 423 survivors and 195 caregivers at 3 months and to 311 of 390 survivors and 184 caregivers at 12 months in the districts with and without interventional programs.

Results
—At 3 months, fewer patients in the districts with active programs (41%) were depressed than in the control districts (54%) (odds ratio, 0.59; 95% confidence interval, 0.37 to 0.94), and the difference was maintained at 12 months (42% versus 55%) (odds ratio, 0.55; 95% confidence interval, 0.34 to 0.88). Univariate risk factors for depression at 3 months were female sex and severe prognostic score at the onset of stroke (≤14 points) on the Scandinavian Stroke Scale (SSS). Only SSS prognostic score and age emerged as significant independent contributors to depression on both linear and logistic multivariate analyses. There was no significant difference in the depression rate of caregivers between districts with active programs (42%) and those without such programs (41%) at 3 months; at 12 months the results were the same (39% in districts with active programs versus 42% in those without such programs). However, at 12 months there were significantly more severely depressed caregivers in districts without active programs than in districts with such programs (
P
.036). Poor Rankin scale score (grades III through V) and severe SSS long-term score (≤42 points) at 3 months among the patients were associated with depression of the caregivers at 3 months in the univariate analysis. Poor Rankin Scale score of the patients was independently associated with the depression of their caregivers at 3 months on multivariate logistic regression analysis.

Conclusions
—Depression was common among stroke survivors and among their caregivers at 3 months, and its rate did not decrease at 1-year follow-up. The lower depression rate in districts with active programs compared to those without supports the idea that outpatient rehabilitation and support provided by local divisions of the FHA may be an effective way of decreasing the rate of depression after stroke.
The Greater Cincinnati/Northern Kentucky Stroke Study
Authors: Broderick Joseph , Brott Thomas , Kothari Rashmi , Miller Rosie , Khoury Jane , Pancioli Arthur , Gebel James , Mills Debbie , Minneci Laura , Shukla Rakesh
Published: June 2011

Background and Purpose
—The Greater Cincinnati/Northern Kentucky Stroke Study was designed to be the first large, population-based metropolitan study of temporal trends in stroke incidence rates and outcome within a biracial population.

Methods
—We are identifying all hospitalized and autopsied cases of stroke and transient ischemic attack (TIA) among the 1.3 million inhabitants of a five-county region of Greater Cincinnati/Northern Kentucky for the period 7/1/93–6/30/94. We have already prospectively monitored for out-of-hospital stroke and TIAs for this same time period at 128 screening sites, including a random sample of all primary care physicians and nursing homes in the region. We have already identified all hospitalized and autopsied cases of stroke and TIA among blacks for 1/1/93–6/30/93 and report preliminary incidence rates for this 6-month period.

Results
—The overall incidence rate for all first-ever hospitalized or autopsied stroke (excluding TIAs) among blacks in the Greater Cincinnati region was 288 per 100 000 (95% CI, 250 to 325, age- and sex-adjusted to 1990 US population). The overall incidence rate for first-ever and recurrent stroke (excluding TIAs) was 411 per 100 000 (95% CI, 366 to 456). By comparison, the overall incidence rate of first-ever stroke among whites in Rochester, Minn, during the period 1985–1989 was 179 per 100 000 (95% CI, 164 to 194, age- and-sex adjusted to 1990 US population). The incidence rates among blacks in Greater Cincinnati were substantially greater than the rates among whites in Rochester, Minn, for all age categories except ages 75 and older, for which the rates were similar.

Conclusions
—We conservatively estimate that 731 100 first-ever or recurrent strokes occurred in the United States during 1996. Studies of first-ever as well as total stroke among biracial and representative populations are critical for understanding temporal trends in the incidence rate and the burden of stroke in the US population.
Permanent Cortical Damage Detected by Flumazenil Positron Emission Tomography in Acute Stroke
Authors: Heiss Wolf-Dieter , Grond Martin , Thiel Alexander , Ghaemi Mehran , Sobesky Jan , Rudolf Jobst , Bauer Bernd , Wienhard Klaus
Published: June 2011

Background and Purpose
—Therapy of acute ischemic stroke can only be effective as long as neurons are viable and tissue is not infarcted. Since γ-aminobutyric acid receptors are abundant in the cortex and sensitive to ischemic damage, specific radioligands to their subunits, the central benzodiazepine receptors (BZR), may be useful as indicators of neuronal integrity and as markers of irreversible damage. To test this hypothesis we studied the binding of the BZR ligand [
11
C]flumazenil (FMZ) early after ischemic stroke in comparison to the extent of final infarcts and hypometabolic cortical areas.

Methods
—In 10 patients cerebral blood flow, cerebral metabolic rate for oxygen (CMRO
2
), oxygen extraction fraction (OEF), and FMZ binding were studied by positron emission tomography 3.5 to 16 hours after onset of their first hemispheric stroke. Early changes in flow, oxygen metabolism, and FMZ binding were compared with permanent disturbances in glucose metabolism, and the size of the final infarcts was determined on MRI or CT 12 to 22 days after the stroke.

Results
—In all patients except one cerebral blood flow was disturbed, with marked decreases in eight and a hyperperfusion in one patient corresponding to the location of neurological deficits. In these areas CMRO
2
was also reduced but to a variable degree, inducing highly variable OEF. Areas with markedly decreased CMRO
2
(<60 μmol/100 g per minute) corresponded to regions with decreased FMZ binding (<4.0 times the mean value in the white matter). In all patients the final cortical infarcts were visible on the early FMZ images. Infarcts could be discriminated from noninfarcted cortex by decreased FMZ binding despite a wide range of OEF. In finally hypometabolic cortex FMZ binding was initially decreased or normal, with OEF covering a wide range; this suggested neuronal loss and/or deactivation as the cause of metabolic disturbance. Additionally, a highly significant correlation was found between FMZ distribution within the first 2 minutes after injection and regional cerebral blood flow.

Conclusions
—These results demonstrate that permanently and irreversibly damaged cortex can be detected by reduced FMZ binding early after stroke. Since FMZ distribution additionally images regional cerebral perfusion, BZR radioligands have a potential as clinically useful tracers in patients with acute ischemic stroke. The evidence of tissue damage furnished by these tracers might be of relevance for the selection of individual therapeutic strategies.
Low Molecular Weight Iron in Cerebral Ischemic Acidosis In Vivo
Authors: Lipscomb Diane C. , Gorman Linda G. , Traystman Richard J. , Hurn Patricia D.
Published: June 2011

Background and Purpose
—Iron-catalyzed radical generation is a potentially significant mechanism by which extensive tissue acidosis exacerbates brain injury during ischemia/reperfusion. We hypothesized that levels of low-molecular-weight (LMW) iron increase during in vivo global cerebral ischemia in a pH-dependent manner, potentially catalyzing oxidant injury. The present study quantified regional differences in LMW iron during global cerebral incomplete ischemia and determined whether augmenting the fall in ischemic tissue pH with hyperglycemia also amplifies free iron availability.

Methods
—Dogs anesthetized with pentobarbital-fentanyl were treated with 30 minutes of global incomplete cerebral ischemia produced by intracranial pressure elevation. Cerebral energy metabolites (ATP, phosphocreatine) and intracellular pH (pH
i
) were measured by
31
P magnetic resonance spectroscopy. Preischemic plasma glucose level was manipulated to titrate end-ischemic pH
i
. After ischemia, brains were perfused with cold phosphate-buffered saline solution; then 16 different brain areas were sampled, filtered to separate the LMW fraction (<30 000 D), and assayed by rapid colorimetric assay for tissue iron. Total iron, LMW iron, and protein in each sample were measured in sham-operated (no ischemia, n=8), normoglycemic ischemia (ISCH [glucose 7±4 mmol/L], n=7), and hyperglycemic (GLU-ISCH [glucose 31±3 mmol/L], n=9) groups.

Results
—High-energy phosphates fell to near zero values in both ISCH and GLU-ISCH groups by 30 minutes but remained unchanged in the sham-operated group. As expected, pH
i
decreased during ischemia but to a greater extent in GLU-ISCH (6.20±0.05 in ISCH, 6.08±0.04 in GLU-ISCH,
P
<.05). Iron could be detected in all areas of the brain in sham-operated animals, with the highest amounts obtained from subcortical areas such as the hippocampus, pons, midbrain, and medulla. Total iron was higher in ISCH relative to sham-operated animals and higher in cortex and pons relative to GLU-ISCH. Regional LMW (as a percentage of total iron; LMW/total iron) was elevated in numerous brain areas in ISCH, including cortical gray matter, cerebellum, hippocampus, caudate, and midbrain. LMW/total iron was higher in GLU-ISCH versus ISCH in cortical gray matter only. In other brain areas, ischemic LMW/total iron was equivalent in glucose-treated or normoglycemic animals (white matter, thalamus, pons, medulla) or lower in the glucose-treated group (cerebellum, hippocampus, caudate, midbrain).

Conclusions
—These data demonstrate that levels of total and LMW iron increase with global cerebral ischemia in the majority of cortical and subcortical regions of normoglycemic brain. However, exacerbation of ischemic acidosis via glucose administration does not increase tissue iron and produces a greater increase in the LMW fraction in cortical gray matter only. In other brain regions, total and LMW iron availability is similar to that of nonischemic animals.
Combating Hyperthermia in Acute Stroke
Authors: Ginsberg Myron D. , Busto Raul
Published: June 2011

Background
—Moderate elevations of brain temperature, when present during or after ischemia or trauma, may markedly worsen the resulting injury. We review these provocative findings, which form the rationale for our recommendation that physicians treating acute cerebral ischemia or traumatic brain injury diligently monitor their patients for incipient fever and take prompt measures to maintain core-body temperature at normothermic levels.

Summary of Review
—In standardized models of transient forebrain ischemia, intraischemic brain temperature elevations to 39°C enhance and accelerate severe neuropathological alterations in vulnerable brain regions and induce damage to structures not ordinarily affected. Conversely, the blunting of even mild spontaneous postischemic hyperthermia confers neuroprotection. Mild hyperthermia is also deleterious in focal ischemia, particularly in reversible vascular occlusion. The action of otherwise neuroprotective drugs in ischemia may be nullified by mild hyperthermia. Even when delayed by 24 hours after an acute insult, moderate hyperthermia can still worsen the pathological and neurobehavioral outcome. Hyperthermia acts through several mechanisms to worsen cerebral ischemia. These include (1) enhanced release of neurotransmitters; (2) exaggerated oxygen radical production; (3) more extensive blood-brain barrier breakdown; (4) increased numbers of potentially damaging ischemic depolarizations in the focal ischemic penumbra; (5) impaired recovery of energy metabolism and enhanced inhibition of protein kinases; and (6) worsening of cytoskeletal proteolysis. Recent studies demonstrate the feasibility of direct brain temperature monitoring in patients with traumatic and ischemic injury. Moderate to severe brain temperature elevations, exceeding core-body temperature, may occur in the injured brain. Cerebral hyperthermia also occurs during rewarming after hypothermic cardiopulmonary bypass procedures. Several studies have now shown that elevated temperature is associated with poor outcome in patients with acute stroke. Finally, recent clinical trials in severe closed head injury have shown a beneficial effect of moderate therapeutic hypothermia.

Conclusions
—The acutely ischemic or traumatized brain is inordinately susceptible to the damaging influence of even modest brain temperature elevations. While controlled clinical investigations will be required to establish the therapeutic efficacy and safety of frank hypothermia in patients with acute stroke, the available evidence is sufficiently compelling to justify the recommendation, at this time, that fever be combated assiduously in acute stroke and trauma patients, even if “minor” in degree and even when delayed in onset. We suggest that body temperature be maintained in a safe normothermic range (eg, 36.7°C to 37.0°C [98.0°F to 98.6°F]) for at least the first several days after acute stroke or head injury.
Adverse Effect of Nighttime Blood Pressure on the Outcome of Lacunar Infarct Patients
Authors: Yamamoto Yasumasa , Akiguchi Ichiro , Oiwa Kaiyo , Hayashi Masamichi , Kimura Jun
Published: June 2011

Background and Purpose
—Antihypertensive therapy has dramatically reduced the incidence of stroke recurrence; however, recent studies have suggested that the excessive lowering of blood pressure (BP) could cause ischemic cerebral lesions. We conducted a prospective study using MRI and ambulatory blood pressure monitoring to elucidate the appropriate BP control level for the prevention of silent and symptomatic cerebral infarction.

Methods
—We studied 105 patients with symptomatic lacunar infarcts who underwent repeated MRI and 24-hour BP monitoring in the period between the two MRI examinations. The patients were divided into five groups according to their outcome as follows: group 1, those who showed neither symptomatic episodes nor the development of new silent lesions detected by repeated MRI; group 2, those who only showed the development of silent lacunae; group 3, those who showed development of diffuse white matter lesions only; group 4, those who showed the development of both silent lacunae and diffuse white matter lesions; and group 5, those who showed symptomatic cerebrovascular disease. Groups 2 through 5 were then compared with group 1 with respect to the ambulatory BP values.

Results
—The average follow-up period was 3.2±2.6 years (mean±SD). In all patients in group 4 and group 5, nighttime systolic BPs were significantly higher than in group 1 (both
P
<.01), and the magnitude of the nocturnal systolic BP dip and diastolic BP dip in group 4 and group 5 were significantly smaller than in group 1 (all
P
<.01). In patients who took antihypertensive agents, the 24-hour systolic and diastolic BPs and nighttime systolic and diastolic BPs in group 4 were significantly higher than in group 1 (
P
<.01,
P
<.01,
P
<.001,
P
<.01, respectively). The magnitude of the nocturnal systolic and diastolic BP dip in group 5 was significantly smaller than in group 1 (both
P
<.01).

Conclusions
—A high average ambulatory BP, especially nighttime BP, and a reduced nocturnal BP dip may have an adverse effect on the development of silent ischemic lesions and symptomatic stroke attack in patients with lacunar infarcts.
Increased Workload Enhances Force Output During Pedaling Exercise in Persons With Poststroke Hemiplegia
Authors: Brown D. A. , Kautz S. A.
Published: June 2011

Background and Purpose
—A principle of poststroke rehabilitation is that effort should be avoided since it leads to increased spasticity and produces widespread associated abnormal reactions. Although weakness also contributes to movement dysfunction after a stroke, it has been feared that heightened activity levels during strength training will further exacerbate the abnormal tone imbalance present in spastic hemiplegia. The purpose of this study was to test this hypothesis by quantifying the effects of increased workload on motor performance during different speeds of pedaling exercise in persons with poststroke hemiplegia.

Methods
—Twelve healthy elderly subjects and 15 subjects with poststroke hemiplegia of greater than 6 months since onset were tested. The experimental protocol consisted of having subjects pedal at 12 randomly ordered workload and cadence combinations (45-J, 90-J, 135-J, and 180-J workloads at 25, 40, and 55 rpm). Pedal reaction forces were measured and used to calculate work done by each leg, including net positive and negative components. An electromyogram was recorded from seven leg muscles.

Results
—The main finding was that net mechanical work done by the plegic leg increased as workload increased in 75 of 81 instances without increasing the percentage of inappropriate muscle activity.

Conclusions
—This study provides evidence that persons with hemiplegia increase force output by their plegic limb when pedaling against higher workloads without exacerbation of impaired motor control. Therefore, exertional pedaling exercise is a beneficial intervention for achieving gains in muscular force output without worsening motor control impairments.
Effectiveness of Superficial Temporal Artery–Middle Cerebral Artery Anastomosis in Adult Moyamoya Disease
Authors: Okada Yoshikazu , Shima Takeshi , Nishida Masahiro , Yamane Kanji , Yamada Tohru , Yamanaka Chie
Published: June 2011

Background and Purpose
—The efficacy of superficial temporal artery–middle cerebral artery (STA-MCA) anastomosis in adult moyamoya disease was evaluated by clinicopathophysiological studies.

Methods
—Fifteen patients with cerebral ischemic attacks (ischemia group) and 15 patients with intracranial hemorrhages (hemorrhage group) were investigated. Clinicoangiographic features and regional cerebral blood flow (rCBF) of the MCA territory were preoperatively and postoperatively investigated, and cortical arterial pressure (CAP) and anastomotic blood flow (AF) were intraoperatively measured.

Results
—In the ischemia group, the preoperative rCBF of 38.4 mL/100 g per minute was significantly increased to 42.1 mL/100 g per minute with a diminution of angiographic moyamoya vessels in 67% of patients after surgery. The mean CAP and AF were 25.6 mm Hg and 34.7 mL/min, respectively. Proximal and distal cerebral vascular resistance (PCVR=[Mean Systemic Arterial Blood Pressure−Mean CAP]/rCBF and DCVR=[Mean CAP/rCBF]) were 1.78 and 0.68, respectively. One patient died perioperatively as a result of intracerebral hemorrhage. During follow-up (mean, 67 months), 12 of 14 patients recovered without neurological deficits, 1 was moderately disabled because of the initial insult, and another patient experienced an intracerebral hemorrhage but recovered fully. In the hemorrhage group, the preoperative rCBF of 38.0 mL/100 g per minute was significantly increased to 42.7 mL/100 g per minute with a diminution of moyamoya vessels in 60% after surgery. The mean CAP and AF were 29.1 mm Hg and 24.1 mL/min, respectively. PCVR and DCVR were 1.72 and 0.77, respectively. One patient became hemiparetic because of perioperative intracerebral hemorrhage. During follow-up (mean, 94 months), 3 patients had fatal intracranial hemorrhages, 10 had good recoveries, and 2 had moderate disabilities.

Conclusions
—This study revealed a high PCVR and a very low DCVR in both the ischemia and hemorrhage groups of patients. STA-MCA anastomosis partially normalized cerebral circulation and decreased moyamoya vessels but did not completely prevent rebleeding.
Patterns of Lateral Medullary Infarction
Authors: Kim Jong S. , Lee Jay H. , Choi Choong G.
Published: June 2011

Background and Purpose
—Correlation of MRI findings with various vascular pathologies has rarely been attempted in patients with lateral medullary infarction (LMI). The aim of the present study was to correlate the diverse MRI lesions with the vascular lesions seen on conventional cerebral angiography in LMI.

Methods
—The subjects included 34 patients with LMI who underwent both MRI and conventional angiography. We analyzed the risk factors, clinical features, MRI findings, and angiography results. The size of the infarction was also measured. We attempted to correlate the MRI findings with the vascular lesions shown in the angiograms.

Results
—Presumed causes for infarction were atherothrombosis in 19 patients, arterial dissection in 8, cardiogenic embolism in 3, moyamoya disease in 1, small-vessel disease in 1, and embolism of unknown source in 2. Isolated posterior inferior cerebellar artery (PICA) disease (n=8) was usually associated with atherothrombosis and correlated with thin, round, or diagonal band–shaped lesions in the lateral-superficial area of the caudal medulla and/or dorsolateral portion of the rostral-middle medulla. Short-segment distal vertebral artery (VA) disease (n=9) was usually due to atherothrombosis and correlated with small lateral caudal and/or medium-sized, diagonal band–shaped rostral-middle medullary lesions. There were 13 patients with long-segment VA disease sparing (n=8) or involving (n=5) the proximal part of the VA with concomitant occlusion of the PICA in 7 patients. This vascular lesion produced either large MRI lesions extending ventrally (n=5; 4 were associated with VA dissection) or small lesions mimicking those produced by isolated PICA disease (n=8; 6 were associated with atherothrombosis and 1 patient had moyamoya disease). These large MRI lesions characteristically produced bilateral or contralateral trigeminal sensory involvement. Normal angiogram (n=4; 3 patients were presumed to have cardiac embolism, one lesion was associated with small-vessel infarction) was associated with small, round lesions that produced minor and fragmentary symptoms. Among these subgroups, the size of the infarct in the patients with long-segment VA disease due to dissection was significantly larger than that of the patients with other vascular lesions.

Conclusions
—Our data suggest that the heterogeneous MRI lesions (and consequent clinical syndromes) of LMI are correlated with diverse angiographic findings, which in turn are due to different pathogenic mechanisms: etiology, location and size of the involved vessels, speed of the lesion development, and status of collateral channels. Generally, infarcts related to multiple vessel involvement, dissection, and poor collateral circulation are larger than those associated with single-vessel disease, long-standing atherothrombosis/cardiac embolism, and good collateralization.
Alterations of Neuropsychological Function and Cerebral Glucose Metabolism After Cardiac Surgery Are Not Related Only to Intraoperative Microembolic Events
Authors: Jacobs A. , Neveling M. , Horst M. , Ghaemi M. , Kessler J. , Eichstaedt H. , Rudolf J. , Model P. , Bönner H. , de Vivie E. R. , Heiss W.-D.
Published: June 2011

Background and Purpose
—High-intensity transient signals (HITS) during cardiac surgery are capable of causing encephalopathy and cognitive deficits. This study was undertaken to determine whether intraoperative HITS cause alterations of neuropsychological function (NPF) and/or cerebral glucose metabolism (CMRGlc), even in a low-risk patient group, and whether induced changes are interrelated.

Methods
—Eighteen patients without signs of cerebrovascular disease underwent elective coronary artery bypass grafting (CABG), and two of these additionally underwent valve replacement in normothermia. Intraoperatively, HITS were recorded by means of transcranial Doppler ultrasonography (TCD). Perioperatively, NPF and CMRGlc were assessed using a standardized complex test battery and positron emission tomography with
18
F-2-fluoro-2-deoxy-
d
-glucose (FDG-PET), respectively.

Results
—Intraoperatively, the number of HITS ranged from 90 to 1710 per patient and hemisphere, more on the right side than on the left (
P
<.05). HITS occurred primarily during cardiopulmonary bypass (71.3%) and, to a lesser extent, during aortic manipulation (22.2%). Changes in global and regional CMRGlc between first (one day preoperatively) and second (8 to 12 days postoperatively) FDG-PET scans were mild. No correlations were found between the number of HITS, age of patient, duration of cardiac ischemia or cardiopulmonary bypass and the changes in CMRGlc. In patients with recorded HITS and a postoperative decrease of regional CMRGlc (n=11), the maximal decrease of rCMRGlc in each hemisphere below the individual global change of CMRGlc correlated with the number of HITS (
r
=−0.46,
P
<.05). Limitations in NPF occurred 8 to 12 days postoperatively, resolved within 3 months, and were not found to be correlated to the absolute number of HITS or changes in CMRGlc.

Conclusions
—HITS during cardiac surgery can cause alterations of both NPF and CMRGlc, even in a low-risk patient group. However, the number of HITS and changes in NPF and CMRGlc are not necessarily interrelated, which indicates that (1) the location of brain damage related to HITS is more important for the development of NPF than is the absolute number of HITS, and (2) factors in addition to HITS might contribute to surgery-related brain damage.
Drug-Induced Neuroprotection From Global Ischemia Is Associated With Prevention of Persistent but Not Transient Activation of Nuclear Factor-κB in Rats
Authors: Clemens James A. , Stephenson Diane T. , Yin Tinggui , Smalstig E. Barry , Panetta Jill A. , Little Sheila P.
Published: June 2011

Background and Purpose
—Nuclear factor-κB (NF-κB) is an oxidative stress responsive transcription factor that is transiently activated in most forebrain neurons in response to transient global ischemia. However, in hippocampal CA1 neurons destined to die, NF-κB remains persistently activated. The present study was performed to determine whether an antioxidant (
LY231617
) that afforded neuroprotection in previous studies had any effect on NF-κB activation in hippocampal CA1 neurons after global ischemia.

Methods
—Rats were subjected to 30 minutes of forebrain ischemia by 4-vessel occlusion (4-VO) and killed at 24 and 72 hours after ischemia. LY231617 was administered orally at a dose of 50 mg/kg 30 minutes before 4-VO and again 4 hours after 4-VO. Neuronal damage was evaluated in sections stained with cresyl violet. Other sections were immunostained with antibodies to NF-κB p50 to assess nuclear localization. An electrophoretic mobility shift assay was performed on nuclear extracts from sham- and LY231617-treated rats at 24 and 72 hours after ischemia.

Results
—The administration of
LY231617
had a significant protective effect on hippocampal CA1 neurons at 72 hours after ischemia (control group, 16±7 neurons/mm; treated group, 294±35 neurons/mm,
P
<.02) and prevented nuclear translocation of activated NF-κB as normally seen at 72 hours after ischemia in untreated controls. In contrast, the untreated controls showed activated NF-κB at 72 hours after ischemia. At 24 hours after ischemia, both the control group and the
LY231617
group showed intense nuclear localization of NF-κB.

Conclusions
—Activation of NF-κB in vitro has been reported to promote proapoptotic as well as antiapoptotic mechanisms, depending on the cell type being investigated. In the present in vivo study, the role of the transient activation of NF-κB observed at 24 hours may be responsible for the induction of protective factors in neurons that survive the ischemic insult, whereas the persistent activation of NF-κB in hippocampal neurons could be responsible for the induction of proteins that result in CA1 neuronal death.
Susceptibility to Cerebral Infarction in the Stroke-Prone Spontaneously Hypertensive Rat Is Inherited as a Dominant Trait
Authors: Gratton Julie A. , Sauter Andre , Rudin Markus , Lees Kennedy R. , McColl John , Reid John L. , Dominiczak Anna F. , Macrae I. Mhairi
Published: June 2011

Background and Purpose
—Susceptibility to cerebral infarction was compared in stroke-prone spontaneously hypertensive (SHRSP), normotensive Wistar-Kyoto (WKY) rats, and F
1
hybrids derived from a SHRSP/WKY cross.

Methods
—The proximal left middle cerebral artery (MCA) was occluded under anesthesia and infarct volume assessed 24 hours later by magnetic resonance imaging and confirmed 5 days later by quantitative histopathology. Total hemispheric infarct volume was expressed as a percentage of the total brain volume.

Results
—Infarct volumes measured by MRI in adult SHRSP (19.5±2.0%) and F
1
hybrid rats (19.4±1.9%) were significantly greater than in WKY (11.1±2.4; CI [6.07, 10.76]) and (5.93, 10.52), respectively,
P
<.001). Sensitivity to an ischemic insult was unrelated to blood pressure: although systolic blood pressures differed between young versus adult male SHRSP and between female versus male SHRSP and F
1
hybrids, infarct volumes were equal. A close correlation was found between infarct volumes measured by MRI and histology (
r
=.92,
P
<.0001).

Conclusions
—Outcome to MCA occlusion (MCAO) measured with MRI provides a reproducible and nonterminal quantitative phenotypic marker of stroke susceptibility in the SHRSP. This is the first study to employ MCAO with MRI to quantify stroke susceptibility in F
1
hybrid rats and indicates a dominant mode of inheritance for this phenotype.
Brain Involvement in Scleroderma
Authors: Héron Emmanuel , Fornes Paul , Rance Arnaud , Emmerich Joseph , Bayle Olivier , Fiessinger Jean-Noël
Published: June 2011

Background
—Neuropathological data are very scarce in systemic sclerosis and fail to demonstrate primary changes in the brains of such patients.

Case Descriptions
—A 41-year-old woman with CREST syndrome developed signs of dementia after an episode of severe dehydration and died two months later of septic shock. A 63-year-old woman with CREST syndrome and a history of two unexplained transient ischemic attacks had had balance disorders since age 62. She died of severe pulmonary hypertension. In both cases, the autopsy showed extensive wall calcification of small arteries and arterioles in the brain, primarily in the basal ganglia, and also in the frontal lobes and the cerebellar area in the second case. No known cause of cerebrovascular calcification was found in either patient.

Conclusion
—The neuropathological findings in these two patients suggest that systemic sclerosis may induce primary vascular changes in the brain, of which calcification may be a marker.
Effect of a Therapeutic Intervention for the Hemiplegic Upper Limb in the Acute Phase After Stroke
Authors: Feys Hilde M. , De Weerdt Willy J. , Selz Beat E. , Cox Steck Gail A. , Spichiger Ruth , Vereeck Luc E. , Putman Koen D. , Van Hoydonck Gustaaf A.
Published: June 2011

Background and Purpose
—Arm function recovery is notoriously poor in stroke patients. The effect of treatment modalities, particularly those directed at improving upper limb function, has been studied primarily in chronic stroke patients. The purpose of this study was to investigate the effect of a specific therapeutic intervention on arm function in the acute phase after stroke.

Methods
—In a single-blind, randomized, controlled multicenter trial, 100consecutive patients were allocated to either an experimental group that received an additional treatment of sensorimotor stimulation or to a control group. The intervention was applied for 6 weeks. Patients were evaluated for level of impairment (Brunnström-Fugl-Meyer test) and disability (Action Research Arm test, Barthel Index) before, midway, and after the intervention period and at follow-up 6 and 12 months after stroke.

Results
—Patients in the experimental group performed better on the Brunnström-Fugl-Meyer test than those in the control group throughout the study period, but differences were significant only at follow-up. Results on the Action Research Arm test and Barthel Index revealed no effect at the level of disability. The effect of the therapy was attributed to the repetitive stimulation of muscle activity. The treatment was most effective in patients with a severe motor deficit and hemianopia or hemi-inattention. No adverse effects due to the intervention were found.

Conclusions
—Adding a specific intervention during the acute phase after stroke improved motor recovery, which was apparent 1 year later. These results emphasize the potential beneficial effect of therapeutic interventions for the arm.
Treatment With the Competitive NMDA Antagonist GPI 3000 Does Not Improve Outcome After Cardiac Arrest in Dogs
Authors: Helfaer Mark A. , Ichord Rebecca N. , Martin Lee J. , Hurn Patricia D. , Castro Alejandro , Traystman Richard J.
Published: June 2011

Background and Purpose
—We previously showed that treatment with a competitive
N
-methyl-
d
-aspartate (NMDA) receptor antagonist GPI-3000 (GPI) improved short-term physiological recovery after incomplete global cerebral ischemia complicated by dense acidosis. We tested the hypothesis that GPI administered after resuscitation from cardiac arrest would improve a more long-term recovery as measured by neurobehavioral assessment and neuropathology 4 days after resuscitation.

Methods
—Anesthetized dogs were subjected to 7 minutes of cardiac arrest followed by vest cardiopulmonary resuscitation. Neurobehavioral outcomes were scored daily on a score ranging from 0 (normal) to 500 (worst). On the fourth day, the animals were killed, and neuropathology was evaluated in a blinded manner in the hippocampus and the neocortex by hematoxylin and eosin staining and by determination of percentage of injured neurons. Three groups of animals were treated in a randomized, blinded protocol with either saline (SAL), low-dose GPI (5 mg/kg followed by 1 mg/kg per hour for 2 hours), or high-dose GPI (25 mg/kg, followed by 5 mg/kg per hour for 2 hours).

Results
—The mortality rate was higher in animals receiving GPI than in saline-treated control animals (4 of 15 deaths in SAL, 6 of 15 in the low-dose GPI group, and 9 of 18 in the high-dose GPI group). Neurobehavioral scores were depressed in GPI-treated animals compared with saline-treated control animals in a dose-dependent manner, with 96-hour scores of essentially normal (9±2) in saline-treated animals compared with those animals with significant impairment (181±47) treated with high-dose GPI. Neuropathological damage in the neocortex was most severe in GPI-treated animals, with the percentage of injured neurons dependent on the dose: 8.3%±2.7% SAL, 13.2%±6.4% low-dose GPI, and 39.4%±10.1%, high-dose GPI. CA1 neuronal damage was severe regardless of treatment.

Conclusions
—Contrary to results seen in experimental global and focal cerebral ischemia, in which NMDA receptor antagonism may improve responses to injury, receptor antagonism with GPI does not improve brain outcome after cardiac arrest and resuscitation in the dog. Behavioral and histological outcomes both were worsened by GPI treatment at two doses, and mortality was higher relative to saline control treatment. We speculate that systemic drug effects, as well as potential neurotoxicity of the drug under ischemic conditions, may be responsible for the deleterious outcomes observed in our cardiac arrest model.
A Novel Endothelin Antagonist, A-127722, Attenuates Ischemic Lesion Size in Rats With Temporary Middle Cerebral Artery Occlusion
Authors: Tatlisumak Turgut , Carano Richard A. D. , Takano Kentaro , Opgenorth Terry J. , Sotak Christopher H. , Fisher Marc
Published: June 2011

Background and Purpose
—Endothelins (ETs) are potent vasoconstrictors. Plasma ET levels increase during acute brain ischemia and may worsen the ischemic damage. Diffusion-weighted MRI (DWI) and perfusion imaging (PI) are powerful tools for evaluation of acute cerebral ischemia. We studied the effects of A-127722, a novel ET
A
-selective ET antagonist, on cerebral ischemic lesion size using 2,3,5-triphenyltetrazolium chloride (TTC) staining postmortem, on acute ischemic lesion development with DWI, and on the cerebral circulation using PI.

Methods
—Twenty male Sprague-Dawley rats received either 5 mg/kg of A-127722 or vehicle (n=10 per group) intravenously 30 minutes and subcutaneously 4 hours after middle cerebral artery occlusion (MCAO). Whole-brain DWI and single-slice PI were done before initiation of treatment and repeated frequently thereafter up to 4 hours after MCAO. The animals were reperfused in the MRI scanner 90 minutes after the onset of MCAO. At 24 hours the animals were killed, and the brains were cut into six 2-mm-thick slices and stained with 2% TTC. Percent hemispheric lesion volume (%HLV) was calculated for each animal.

Results
—Physiological parameters, body weight, neurological scores, and premature mortality (2 versus 2) did not differ between the two groups. No hypotension, abnormal behavior, or other adverse effects were seen. TTC-derived %HLV was 25.3±5.6% for controls and 16.2±9.6% for treated animals (36% reduction,
P
<.02). Six animals in each group had successful reperfusion as shown by PI. Among these animals, %HLV was 23.2±3.1% for controls and 9.3±4.4% for treated animals (60% reduction,
P
=.0001). The beneficial effect of A-127722 was limited to animals in which successful reperfusion was demonstrated. No difference in PI-detected perfusion deficit size was observed between the groups. DWI did not demonstrate significant in vivo lesion size differences.

Conclusions
—A-127722 significantly reduced ischemic lesion size in rats without observable adverse effects. It is not clear whether the effect was due to vasodilatation of collateral arterioles not detectable by PI or whether A-127722 has neuroprotective properties that are independent of vascular effects.
Dietary Vitamin E Levels Affect Outcome of Permanent Focal Cerebral Ischemia in Rats
Authors: van der Worp H. B. , Bär P.R. , Kappelle L. J. , de Wildt D. J.
Published: June 2011

Background and Purpose
—A supraphysiological amount of vitamin E in the standard diet of laboratory animals may provide partial protection against cerebral ischemic damage in stroke models. The aim of the present study was to test the effect of dietary vitamin E on infarct volume in rats subjected to permanent focal cerebral ischemia.

Methods
—Male Wistar rats were raised on a vitamin E–deficient diet (n=10) or a control diet containing 62.7 mg vitamin E/kg (n=11) for 13 to 16 weeks, from the age of 3 weeks. The left middle cerebral artery (MCA) was permanently occluded by means of an intraluminal silicone-coated 3–0 suture. Blood flow in the left MCA territory was measured before and after occlusion with laser Doppler flowmetry. The area of infarction was measured in hematoxylin-eosin–stained brain sections by means of an image analysis system. The investigator was not aware of the vitamin E status of the rats.

Results
—Blood flow in the left MCA territory in the second half hour after occlusion was 43±17% and 42±17% (mean±SD) of the baseline value in control and vitamin E–deficient rats, respectively. The mean infarct volume, measured after 48 hours of survival, was 61±19 mm

3

in control rats and 137±76 mm

3

in vitamin E–deficient rats (
P
=0.037).

Conclusions
—After permanent focal cerebral ischemia, the infarct is larger in vitamin E–deficient rats than in rats raised on a diet with the usual, supraphysiological amount of vitamin E. This may have consequences for cerebral ischemia studies with experimental animals.
White Matter Changes in the Gerbil Brain Under Chronic Cerebral Hypoperfusion
Authors: Kurumatani Takahiro , Kudo Takashi , Ikura Yasumitsu , Takeda Masatoshi
Published: June 2011

Background and Purpose
—An animal model of chronic cerebral hypoperfusion was developed with coiled clips applied to both carotid arteries of adult Mongolian gerbils for between 1 week and 2 months. In the brain of this animal model, rarefaction of white matter with dilatation of the ventricles was frequently observed. To better understand the mechanism of white matter alteration under cerebral hypoperfusion, the chronological sequence of molecular changes in the cerebral white matter of the animal model was determined.

Methods
—Specially designed coiled clips were placed around both carotid arteries of Mongolian gerbils to create stenosis without occlusion. Changes in levels of myelin basic protein (MBP) as a marker of myelin, neurofilament H (NFH) as a marker of axonal proteins, and glial fibrillary acidic protein (GFAP) in astroglia after 2 months of cerebral hypoperfusion were analyzed with Western blotting and enzyme-linked immunosorbent assay.

Results
—Western blotting of the white matter after 2 months of hypoperfusion showed that the levels of MBP and NFH decreased, whereas that of GFAP increased. The time course of MBP and NFH changes determined with enzyme-linked immunosorbent assay revealed that the change of MBP preceded that of NFH.

Conclusions
—In the present study it was shown that the damage to myelin precedes that to the axon in the white matter in a chronic cerebral hypoperfusion animal model, suggesting that the change in myelin is the primary pathological event in the cerebral white matter under chronic hypoperfusion. The present study may help in understanding the mechanisms of white matter pathology in leukoaraiosis.
Impact of Medical Treatment on the Outcome of Patients After Aneurysmal Subarachnoid Hemorrhage
Authors: Vermeij Frederique H , Hasan Djo , Bijvoet Henk W. C. , Avezaat Cees J. J.
Published: June 2011

Background and Purpose
—The rationale behind early aneurysm surgery in patients with subarachnoid hemorrhage (SAH) is the prevention of rebleeding as early as possible after SAH. In addition, by clipping the aneurysm as early as possible, one can apply treatment for cerebral ischemia more vigorously (induced hypertension) without the risk of rebleeding. Hypervolemic hemodilution is now a well-accepted treatment for delayed cerebral ischemia. We compared the prospectively collected clinical data and outcome of patients admitted to the intensive care unit in the period 1977 to 1982 with those of patients admitted in the period 1989 to 1992 to measure the effect of the change in medical management procedures on patients admitted in our hospital with SAH.

Methods
—We studied 348 patients admitted within 72 hours after aneurysmal SAH. Patients with negative angiography results and those in whom death appeared imminent on admission were excluded. The first group (group A) consisted of 176 consecutive patients admitted from 1977 through 1982. Maximum daily fluid intake was 1.5 to 2 L. Hyponatremia was treated with fluid restriction (<1 L/24 h). Antihypertensive treatment with diuretic agents was given if diastolic blood pressure was >110 mm Hg. Patients in the second group (172 consecutive patients; group B) were admitted from 1989 through 1992. Daily fluid intake was at least 3 L, unless cardiac failure occurred. Diuretic agents and antihypertensive medications were avoided. Cerebral ischemia was treated with vigorous plasma volume expansion under intermittent monitoring of pulmonary wedge pressure, cardiac output, and arterial blood pressure, aiming for a hematocrit of 0.29 to 0.33. Aneurysm surgery was planned for day 12.

Results
—Patients admitted in group B had less favorable characteristics for the development of cerebral ischemia and for good outcome when compared with patients in group A. Despite this, we found a significant decrease in the frequency of delayed cerebral ischemia in patients of group B treated with tranexamic acid (
P
=0.00005 by log rank test) and significantly improved outcomes among patients with delayed cerebral ischemia (
P
=0.006 by χ
2
test) and among patients with deterioration from hydrocephalus (
P
=0.001 by χ
2
test). This resulted in a significant improvement of the overall outcome of patients in group B when compared with those in group A (
P
=0.006 by χ
2
test). The major cause of death in group B was rebleeding (
P
=0.011 by χ
2
test).

Conclusions
—We conclude that the outcome in our patients with aneurysmal SAH was improved but that rebleeding remains a major cause of death. Patient outcome can be further improved if we can increase the efficacy of preventive measures against rebleeding by performing early aneurysm surgery.
Patent Foramen Ovale Size and Embolic Brain Imaging Findings Among Patients With Ischemic Stroke
Authors: Steiner Michaela M. , Di Tullio Marco R. , Rundek Tanja , Gan Robert , Chen Xun , Liguori Chiara , Brainin Michael , Homma Shunichi , Sacco Ralph L.
Published: June 2011

Background and Purpose
—Although the cause of stroke among patients with patent foramen ovale (PFO) may be due to paradoxical cerebral embolism (PCE), this mechanism is often difficult to prove. The aim of our study was to evaluate the association between brain imaging findings suggestive of embolism and PFO among ischemic stroke patients.

Methods
—As part of the Northern Manhattan Stroke Study, 95 patients with first ischemic stroke over age 39 underwent transesophageal echocardiography (TEE) for evaluation of a cardiac source of embolism. The stroke subtype was determined by modified NINDS Stroke Data Bank criteria. Stroke subtype and MRI/CT imaging data were evaluated blind to the presence of a PFO. These findings were compared between two groups: patients with medium to large PFO (≥2 mm) and small (<2 mm) or no PFO.

Results
—Of the 95 patients who underwent TEE, 31 (33%) had a PFO. The frequency of PFO was significantly greater among patients with cryptogenic infarcts (19 of 42; 45%) compared with patients with determined cause of stroke (12 of 53, 23%;
P
=0.02). Medium to large PFOs were found more often among cryptogenic strokes than among infarcts of determined cause (26% versus 6%;
P
=0.04). Superficial infarcts occurred more often in the group with larger PFOs than in the group with small or no PFOs (50% versus 21%;
P
=0.02). Patients with medium or large PFOs more frequently had occipital and infratentorial strokes (57% versus 27%;
P
=0.02).

Conclusions
—Stroke patients with larger PFOs show more brain imaging features of embolic infarcts than those with small PFOs. Larger PFOs may be more likely to cause paradoxical embolization and may help explain the stroke mechanism among patients with no other definite cause.