bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Potassium Channels in Regulation of Brain Arteriolar Tone
Authors: Horiuchi Tetsuyoshi , Dietrich Hans H. , Tsugane Shinichiro , Dacey Ralph G.
Published: June 2011

Background and Purpose
—Potassium channels are important regulators of resting tone in large cerebral arteries, but their activity and distribution may vary according to vessel location and species studied. In the cerebral microcirculation in vivo, however, these channels appear to be silent at rest. Our goal was to determine the activity of potassium channels of brain arterioles from 2 origins under basal conditions in vitro.

Methods
—Penetrating cerebral (40.9±2.2 μm control diameter) and brain stem (36.2±1.2 μm) arterioles of rats were prepared from middle cerebral and basilar arteries, respectively. The internal diameter of cannulated and pressurized vessel was monitored with the inverted microscope before and after administration of potassium channel inhibitors. In addition, we studied the effect of nitric oxide synthase inhibition on potassium channel activity.

Results
—Cerebral and brain stem arterioles were significantly constricted by 4-aminopyridine and low concentration of BaCl
2
but not by glibenclamide. The addition of
N

ω

-nitro-
l
-arginine to 4-aminopyridine further decreased diameters of both arterioles. Tetraethylammonium ion caused a significant constriction of brain stem but not cerebral arteriole. The brain stem arteriole was further constricted by additional
N

ω

-nitro-
l
-arginine.

Conclusions
—Voltage-dependent and inward-rectifier, but not ATP-sensitive, potassium channels are active under basal conditions of rat cerebral and brain stem arterioles. There is a regional difference in the activity of calcium-activated potassium channels, which, at rest, are open in brain stem but silent in cerebral arterioles. In addition, basal endogenous nitric oxide may not contribute to the activation of voltage-dependent and calcium-activated potassium channels.
Treatment of Acute Ischemic Stroke With the Low-Molecular-Weight Heparin Certoparin
Authors: Diener Hans Christoph , Ringelstein Erich Bernd , von Kummer Rüdiger , Langohr Hans Dieter , Bewermeyer Heiko , Landgraf Helmut , Hennerici Michael , Welzel Dieter , Gräve Michael , Brom Joachim , Weidinger Gottfried
Published: June 2011

Background and Purpose
—To study the safety and efficacy of the low-molecular-weight heparin certoparin, we performed a randomized, double-blind, dose-finding multicenter trial in patients with acute ischemic stroke (Therapy of Patients With Acute Stroke [TOPAS]).

Methods
—We randomized 404 patients to 4 treatment groups within 12 hours of stroke onset: 3000 U anti–factor Xa (aXa) certoparin once daily (treatment group 1); 3000 U aXa twice daily (group 2); 5000 U aXa twice daily (group 3); and 8000 U aXa twice daily (group 4). The primary efficacy variable was the proportion of patients reaching a favorable functional outcome (Barthel Index ≥90 points) at 3 months. CT was performed at trial entry, after 7 days, and on clinical deterioration.

Results
—The proportion of patients with Barthel Index ≥90 was not different between treatment arms (61.5%, 60.8%, 63.3%, and 56.3% in the 4 groups, respectively; intent-to-treat population). European Stroke Scale scores improved in all treatment groups within the first 14 days to a similar extent. During the follow-up of 6 months, percentages of patients with recurrent stroke/transient ischemic attack were 11.0%, 5.9%, 9.7%, and 13.0% in the 4 groups, respectively. Overall mortality was only 7.4%. Two parenchymal cerebral hematomas and 1 extracranial bleeding episode occurred in treatment group 1 versus 1 and 0 in group 2, 2 and 0 in group 3, and 4 and 5 in group 4, respectively. During certoparin treatment, 1 deep vein thrombosis but no pulmonary embolism was observed.

Conclusions
—Dose increase of certoparin up to 8000 U aXa twice daily did not improve the functional outcome of patients with ischemic stroke. Severe bleeding tended to be more frequent in the highest dose group only.
Antisense Oligodeoxynucleotide Inhibition of Tumor Necrosis Factor-α Expression Is Neuroprotective After Intracerebral Hemorrhage
Authors: Mayne M. , Ni W. , Yan H. J. , Xue M. , Johnston J. B. , Del Bigio M. R. , Peeling J. , Power C.
Published: June 2011

Background and Purpose
—Tumor necrosis factor-α (TNF-α) expression is increased in brain after cerebral ischemia, although little is known about its abundance and role in intracerebral hemorrhage (ICH). A TNF-α–specific antisense oligodeoxynucleotide (ORF4-PE) was used to study the extent to which TNF-α expression influenced neurobehavioral outcomes and brain damage in a collagenase-induced ICH model in rat.

Methods
—Male Sprague-Dawley rats were anesthetized, and ICH was induced by intrastriatal administration of heparin and collagenase. Immediately before or 3 hours after ICH induction, ORF4-PE was administered directly into the site of ICH. TNF-α mRNA and protein levels were measured by reverse transcriptase–polymerase chain reaction and immunoblot analyses. Cell death was measured by terminal deoxynucleotidyl transferase–mediated uridine 5′triphosphate-biotin nick end labeling (TUNEL). Neurobehavioral deficits were measured for 4 weeks after ICH.

Results
—ICH induction (n=6) elevated TNF-α mRNA and protein levels (
P
<0.01) at 24 hours after the onset of injury compared with sham controls (n=6). Immunohistochemical labeling indicated that ICH was accompanied by elevated expression of TNF-α in neutrophils, macrophages, and microglia. Administration of ORF4-PE (2.0 nmol) directly into striatal parenchyma, 15 minutes before (n=4) or 3 hours after (n=6) ICH, decreased levels of TNF-α mRNA (
P
<0.001) and protein (
P
<0.01) in the brain tissue surrounding the hematoma compared with animals treated with saline alone (n=6). Mean±SEM striatal cell death (cells per high-powered field) was also reduced in animals receiving ORF4-PE (34.1±5.0) compared with the saline-treated ICH group (80.3±7.50) (
P
<0.001). ORF4-PE treatment improved neurobehavioral deficits observed at 24 hours (
P
<0.001) after induction of ICH (n=6) compared with the untreated ICH group (n=6). This improvement was maintained at 28 days after hemorrhage induction (
P
<0.001).

Conclusions
—These results indicate a pathogenic role for TNF-α during ICH and demonstrate that reducing TNF-α expression using antisense oligodeoxynucleotides is neuroprotective.
Bone Mineral Density in Acute Stroke Patients
Authors: Jørgensen Lone , Engstad Torgeir , Jacobsen Bjarne K.
Published: June 2011

Background and Purpose
—Osteoporosis and stroke share several risk factors, including age, smoking, low physical activity, and hypertension. Thus, low bone mineral density (BMD) and high stroke risk may be related. We examined the relationship between BMD and acute stroke in noninstitutionalized men and women aged ≥60 years.

Methods
—Sixty-three stroke patients (33 women and 30 men) and 188 control subjects from the general population were included. BMD was measured by using dual-energy x-ray absorptiometry at both proximal femurs. The measurements of the stroke patients were performed 6 days after the onset of stroke.

Results
—The BMD at the femoral neck in the female stroke patients was 8% lower than in the control subjects (
P
=0.007). In men, no difference in BMD between the stroke patients and their controls was found. Women with BMD values in the lowest quartile had a higher risk of stroke than women with BMD values in the highest quartile (OR 4.8), and the probability value for linear trend over the quartiles was statistically significant (
P
=0.003). The OR for stroke increased 1.9 per SD (0.13 g/cm
2
) reduction in BMD, and the association between low BMD and stroke in women remained significant when the analysis was adjusted for potential confounders.

Conclusions
—Female, but not male, stroke patients have lower BMD than population controls. Low BMD may predict stroke in women.
Stroke Severity Determines Body Temperature in Acute Stroke
Authors: Boysen Gudrun , Christensen Hanne
Published: June 2011

Background and Purpose
—Several studies have claimed that temperature on admission is of prognostic significance in acute stroke. Experimental studies showing that hyperthermia increases infarct size have lent credibility to this assumption. The aim of the present study was to test the hypothesis that initial body temperature is of importance for stroke outcome.

Methods
—This prospective study included 725 consecutive patients, 584 with cerebral infarcts and 141 with intracerebral hemorrhages, admitted to an acute stroke unit within 6 hours of stroke onset. Time of stroke onset and time of admission were recorded. Body temperature was measured on admission and every 2 hours during the first 24 hours. Patients were divided into 2 groups on the basis of stroke severity on admission: Scandinavian Stroke Scale Score (SSS) ≤25 was defined as major stroke, and SSS >25 was defined as mild to moderate stroke.

Results
—On admission, mean body temperature was normal. In the major stroke patients, body temperature started to rise 4 to 6 hours after stroke onset. At 10 to 12 hours after stroke onset, increased body temperature was found to be related to poor outcome. In mild to moderate stroke, there was no significant rise in temperature. Initial temperature >37.5°C was not related to stroke severity or stroke outcome.

Conclusions
—In major stroke, a significant rise in temperature occurred hours after stroke onset. Severe infarcts and intracerebral hemorrhages caused temperature to rise, whereas initially increased temperature had no influence on stroke severity. Elevated body temperature on admission within 6 hours of stroke onset had no prognostic influence on stroke outcome at 3 months.
Caspase Inhibitors Attenuate Oxyhemoglobin-Induced Apoptosis in Endothelial Cells
Authors: Meguro Toshinari , Chen Betty , Parent Andrew D. , Zhang John H.
Published: June 2011

Background and Purpose
—Our recent study showed that oxyhemoglobin (OxyHb) induces apoptosis in cultured endothelial cells. Apoptosis requires the action of various classes of proteases, including a family of cysteine proteases known collectively as the caspases. This study was undertaken to investigate the effect of 2 caspase inhibitors, Z-VDVAD-FMK and Z-DEVD-FMK, in the protection of endothelial cells from OxyHb-induced apoptosis.

Methods
—Cultured bovine brain microvascular endothelial cells (passages 5 to 9) were exposed to OxyHb (10 μmol/L) for 24 to 72 hours with and without caspase inhibitors. Cell attachment, DNA ladder, Western blotting of poly(ADP-ribose) polymerase (PARP), and caspase activities were measured to confirm the cytotoxic effect of OxyHb and the protective effect of the caspase inhibitors.

Results
—(1) OxyHb produced cell detachment in a time-dependent manner. (2) OxyHb increased caspase-2 and -3 activities, produced DNA ladders, and cleaved PARP in endothelial cells. (3) Z-VDVAD-FMK and Z-DEVD-FMK (100 μmol/L) attenuated OxyHb-induced cell detachment, reduced caspase-2 and -3 activities, abolished OxyHb-induced DNA ladders, and prevented OxyHb-induced cleavage of PARP.

Conclusions
—OxyHb activates caspase-2 and -3 in cultured brain microvessel endothelial cells. Caspase inhibitors attenuated the cytotoxic effect of OxyHb.
Overexpression of Copper-Zinc Superoxide Dismutase Attenuates Acute Activation of Activator Protein-1 After Transient Focal Cerebral Ischemia in Mice
Authors: Huang Chiung-Ying , Fujimura Miki , Chang Yung-Yee , Chan Pak H.
Published: June 2011

Background and Purpose
—Reactive oxygen species (ROS) have been implicated in reperfusion injury after focal cerebral ischemia (FCI). ROS are known to regulate the activity of transcription factors such as activator protein-1 (AP-1), which is a dimer consisting of members of the Jun and Fos families. We investigated the role of ROS in AP-1 activity after FCI using transgenic mice that overexpressed copper-zinc superoxide dismutase (SOD1) and that had reduced infarction volume after FCI.

Methods
—The SOD1 transgenic mice and their wild-type littermates were subjected to middle cerebral artery occlusion and reperfusion by intraluminal suture blockade. After 60 minutes of middle cerebral artery occlusion, mice were allowed to recover for 1, 2, and 4 hours before euthanasia. Protein expression of c-Jun and c-Fos was examined by immunohistochemistry and Western blotting. AP-1 DNA-protein binding activity was assessed by electrophoretic mobility shift assays.

Results
—In wild-type mice, immunohistochemistry demonstrated acute c-Jun and c-Fos activation in ischemic cortex and its outer boundary. Expression of both was reduced in SOD1 transgenic mice. Western blotting confirmed that SOD1 overexpression was associated with reduced c-Jun and c-Fos protein levels in ischemic brain. Electrophoretic mobility shift assays revealed that the ischemia-enhanced DNA binding activity observed in wild-type mice was reduced in SOD1 transgenic mice. Supershift assays indicated that c-Jun participated in the bound AP-1 complex.

Conclusions
—SOD1 overexpression prevents early activation of AP-1 after transient FCI in mice. This may block the expression of downstream target genes that are injurious, thereby reducing the infarction volume after transient FCI in mice.
Resolution of Stroke Deficits Following Contralateral Grafts of Conditionally Immortal Neuroepithelial Stem Cells
Authors: Veizovic Tina , Beech John S. , Stroemer R. Paul , Watson William P. , Hodges Helen
Published: June 2011

Background and Purpose
—Grafts of MHP36 cells have previously been shown to reduce dysfunction after global ischemia in rats. To test their efficacy after focal ischemia, MHP36 cells were grafted 2 to 3 weeks after transient intraluminal middle cerebral artery occlusion (tMCAO) in rats.

Methods
—MHP36 cells were implanted into the hemisphere contralateral to the lesion, with 8 deposits of 3 μL of cell suspension (25 000 cells per microliter). Sham grafted rats received equivalent volumes of vehicle. Three groups, sham-operated controls (n=11), MCAO+sham grafts (n=10), and MCAO+MHP36 grafts (n=11), were compared in 3 behavioral tests.

Results
—In the bilateral asymmetry test, MCAO+MHP36 grafted rats exhibited neglect before grafting but subsequently showed no significant dysfunction, whereas MCAO+sham grafted rats showed stable sensorimotor deficits over 18 weeks relative to controls. MCAO+sham grafted rats demonstrated spontaneous motor asymmetry and increased rotational bias after injection of dopamine agonists. MCAO+MHP36 and control groups exhibited no bias in either spontaneous or drug-induced rotation. In contrast to motor recovery, MCAO+MHP36 grafted rats showed no improvement relative to MCAO+sham grafted rats in spatial learning and memory in the water maze. MCAO produced large striatal and cortical cavitations in both occluded groups. Lesion volume was significantly reduced (
P
<0.05) in the MCAO+MHP36 grafted group. The majority of MHP36 cells were identified within the intact grafted hemisphere. However, MHP36 cells were also seen in the cortex, striatum, and corpus callosum of the lesioned hemisphere.

Conclusions
—MHP36 cells may improve functional outcome after MCAO by assisting spontaneous reorganization in both the damaged and intact hemispheres.
Elevated White Blood Cell Count and Carotid Plaque Thickness
Authors: Elkind Mitchell S. , Cheng Jianfeng , Boden-Albala Bernadette , Paik Myunghee C. , Sacco Ralph L.
Published: June 2011

Background and Purpose
—Elevated leukocyte count has been associated with cardiovascular and cerebrovascular disease in several epidemiological studies. We sought to determine whether white blood cell count (WBC) is associated with carotid plaque thickness in a stroke-free, multiethnic cohort.

Methods
—For this cross-sectional analysis, WBC was measured in stroke-free community subjects undergoing carotid duplex Doppler ultrasound. Maximal internal carotid plaque thickness (MICPT) was measured for each subject. Demographic and potential medical confounding factors were analyzed with linear and logistic regression to calculate the effect of quartile of WBC on MICPT. Odds ratios (ORs) and 95% confidence intervals (CIs) for the effect of quartile of WBC on MICPT ≥75th percentile were calculated. All analyses were stratified by race-ethnicity.

Results
—The mean age of the 1422 subjects was 68.6±10.2 years; 40.0% were men; 24.4% were white, 46.9% Hispanic, and 26.7% black. Among Hispanics, compared with the lowest quartile of WBC, those in the highest quartile had significantly increased MICPT (mean difference=0.30 mm,
P
=0.0086) after adjustment for age, sex, and other atherosclerotic risk factors. There was no significant increase for blacks or whites. The OR for MICPT ≥75th percentile (1.9 mm) was significantly increased for Hispanics (OR, 2.8; 95% CI, 1.4 to 5.6), marginally elevated for black non-Hispanics (OR, 1.6; 95% CI, 0.8 to 3.2), and not increased for white non-Hispanics (OR, 0.5; 95% CI, 0.2 to 1.1).

Conclusions
—Relative elevation in WBC is associated with carotid atherosclerosis, but this relationship differs by race-ethnicity. The association is strongest in Hispanics, intermediate in black non-Hispanics, and not present in white non-Hispanics in this population. Chronic subclinical infection or inflammation may account for this association.
Cerebrovascular Manifestations in 321 Cases of Hereditary Hemorrhagic Telangiectasia
Authors: Maher Cormac O. , Piepgras David G. , Brown Robert D. , Friedman Jonathan A. , Pollock Bruce E.
Published: June 2011

Background and Purpose
—Patients with hereditary hemorrhagic telangiectasia (HHT) are at risk for developing cerebral vascular malformations and pulmonary arteriovenous fistulae. We assessed the risk of neurological dysfunction from these malformations and fistulae.

Methods
—Three hundred twenty-one consecutive patients with HHT seen at a single institution over a 20-year period were studied. Any evidence of prior neurological symptoms or presence of an intracranial vascular malformation was recorded. All cases of possible cerebral arteriovenous malformation were confirmed by conventional arteriography.

Results
—Twelve patients (3.7%) had a history of cerebral vascular malformations. Ten patients had arteriovenous malformations, 1 had a dural arteriovenous fistula, and 1 had a cavernous malformation. Seven patients (2.1%) presented with intracranial hemorrhage, 2 presented with seizures alone, and 3 were discovered incidentally. The average age at the time of symptomatic intracranial hemorrhage was 25.4 years. All patients with a history of intracranial hemorrhage were classified as Rankin grade I or II at a mean follow-up interval of 6.0 years. A history of cerebral infarction or transient ischemic attack was found in 29.6% of patients with HHT and a pulmonary arteriovenous fistula.

Conclusions
—The risk of intracranial hemorrhage is low among people with HHT. Furthermore, a majority of these patients have a good functional outcome after hemorrhage. The data do not suggest a compelling indication for routine screening of patients with HHT for asymptomatic cerebral vascular malformations. By comparison, pulmonary arteriovenous fistulae are a much more frequent cause of neurological symptoms in this population.
Plasma Vitamin C Levels Are Decreased and Correlated With Brain Damage in Patients With Intracranial Hemorrhage or Head Trauma
Authors: Polidori Maria Cristina , Mecocci Patrizia , Frei Balz
Published: June 2011

Background and Purpose
—Free radical hyperproduction may play an important role in brain hemorrhage and ischemia/reperfusion injury. The aims of this study were to assess whether antioxidant depletion occurs after intracranial hemorrhage (ICH) and head trauma (HT) and to evaluate the relation between the diameter of the brain lesion, the degree of the neurological impairment, and any observed antioxidant changes.

Methods
—We measured plasma levels of vitamin C (ascorbic acid, AA), uric acid (UA), vitamin E (α-tocopherol), and ubiquinol-10 in 13 patients with ICH and 15 patients with HT on the day of the brain injury and subsequently every other day up to 1 week. Patients were compared with 40 healthy control subjects.

Results
—ICH and HT patients had significantly lower plasma levels of AA compared with healthy subjects, in contrast to plasma levels of UA, α-tocopherol, and ubiquinol-10. AA levels were significantly inversely correlated with the severity of the neurological impairment as assessed by the Glasgow Coma Scale and the National Institutes of Health Stroke Scale. AA levels were also significantly inversely correlated with the major diameter of the lesion. In addition, mean plasma AA levels were lower in jugular compared with peripheral blood samples obtained from 5 patients.

Conclusions
—These findings suggest that a condition of oxidative stress occurs in patients with head trauma and hemorrhagic stroke of recent onset. The consequences of early vitamin C depletion on brain injury as well as the effects of vitamin C supplementation in ICH and HT patients remain to be addressed in further studies.
C-Reactive Protein in Ischemic Stroke
Authors: Di Napoli Mario , Papa Francesca , Bocola Vittorio
Published: June 2011

Background and Purpose
—There is growing evidence of the prognostic importance of C-reactive protein (CRP) in ischemic stroke. However, the independent value of CRP at different stages after stroke has not been established. Therefore, we assessed the prognostic values of CRP in ischemic stroke. We also compared the relation of CRP at admission and discharge with 1-year outcome.

Methods
—One hundred ninety-three patients were included in a derivation set (n=128) and a validation set (n=65). Serum CRP was measured, within 24 hours after index ischemic stroke, within 48 to 72 hours, and at hospital discharge. We examined the association between the level of CRP at different stages after stroke and outcome. We adjusted for the possible confounding effect using a multivariate Cox proportional hazard model.

Results
—A cutoff point of 1.5 mg/dL for CRP at discharge provided optimum sensitivity and specificity for adverse outcome, based on the receiver operator curves. CRP at admission (hazard ratio [HR] 2.78, 95% CI 1.45 to 5.33;
P
=0.0021) and discharge (HR 9.42, 95% CI 4.27 to 19.05;
P
<0.0001) were predictors of the combined end point of new vascular events or death at 1 year. CRP at hospital discharge was the strongest independent marker of adverse outcome (HR 7.42, 95% CI 2.75 to 20.03;
P
=0.0001). These results were confirmed in the validation set (HR 15.66, 95% CI 3.36 to 72.97;
P
=0.0005).

Conclusions
—CRP is a marker of increased 1-year risk in ischemic stroke. CRP at discharge is better related to later outcome and could be of greater utility for risk stratification. These findings are consistent with the hypothesis that elevated CRP may predict future cardiovascular events or death.
Multiparametric MRI Tissue Characterization in Clinical Stroke With Correlation to Clinical Outcome
Authors: Jacobs Michael A. , Mitsias Panayiotis , Soltanian-Zadeh Hamid , Santhakumar Sunitha , Ghanei Amir , Hammond Rabih , Peck Donald J. , Chopp Michael , Patel Suresh
Published: June 2011

Background and Purpose
—Multiparametric MRI generates different zones within the lesion that may reflect heterogeneity of tissue damage in cerebral ischemia. This study presents the application of a novel model of tissue characterization based on an angular separation between tissues obtained with the use of an objective (unsupervised) computer segmentation algorithm implementing a modified version of the Iterative Self-Organizing Data Analysis Technique (ISODATA). We test the utility of this model to identify ischemic tissue in clinical stroke.

Methods
—MR parameters diffusion-, T2-, and T1-weighted imaging (DWI, T2WI, and T1WI, respectively) were obtained from 10 patients at 3 time points (30 studies) after stroke: acute (≤12 hours), subacute (3 to 5 days), and chronic (3 months). The National Institutes of Health Stroke Scale (NIHSS) was measured, and volumes were obtained from the ISODATA, DWI, and T2WI maps on patients at each time point.

Results
—The acute (≤12 hours) multiparametric ISODATA volume was significantly correlated with the acute (≤12 hours) DWI (
r
=0.96,
P
<0.05; n=10) and chronic (3 months) T2WI volume (
r
=0.69,
P
<0.05; n=10). The ISODATA-defined tissue regions exhibited MR indices consistent with ischemic and/or infarcted tissue at each time point. The acute (≤12 hours) multiparametric ISODATA volumes were significantly correlated (
r
=0.82,
P
<0.009; n=10) with the final NIHSS score. In comparison, the acute (≤12 hours) DWI volumes were less correlated (
r
=0.77,
P
<0.05; n=10) and T2WI volume (≤12h) exhibited a marginal correlation (
r
=0.66,
P
<0.05; n=10) with the final NIHSS score.

Conclusions
—The integrated ISODATA approach to tissue segmentation and classification discriminated abnormal from normal tissue at each time point. The ISODATA volume was significantly correlated with the current MR standards used in the clinical setting and the 3-month clinical status of the patient.
Geographic Distribution of Stroke Incidence Within an Urban Population
Authors: Engström Gunnar , Jerntorp Ingela , Pessah-Rasmussen Hélène , Hedblad Bo , Berglund Göran , Janzon Lars
Published: June 2011

Background and Purpose
—Geographic differences in stroke incidence indicate a potential for prevention. The present study from the city of Malmö, Sweden, sought to investigate whether incidence of stroke in residential areas is related to prevalence of cardiovascular risk factors and socioeconomic circumstances.

Methods
—The Stroke Register in Malmö, Sweden, was used for retrieval of the 3540 patients who suffered a first stroke between 1989 and 1998. The Malmö Diet and Cancer cohort (n=28 466) was used to assess area specific prevalence of hypertension, diabetes, smoking, and being overweight and for computation of a cardiovascular risk score. Socioeconomic circumstances for the 17 administrative areas were expressed in terms of a composite score.

Results
—Standardized stroke incidence ranged among areas from 437 to 743 per 100 000 for men and from 223 to 518 per 100 000 for women. Socioeconomic score correlated significantly with area-specific stroke rates among men (
r
=−0.62,
P
=0.008) and women (
r
=−0.67,
P
=0.004). Incidence of stroke was significantly associated with cardiovascular risk score for each area (men,
r
=0.53,
P
<0.05; women,
r
=0.76,
P
<0.001). The cardiovascular score and the socioeconomic score together accounted for 44% of the geographic variance among men and 63% among women.

Conclusions
—Marked differences occurred in stroke incidence among residential areas within this urban population. High-rate areas were characterized by a higher prevalence of smoking, hypertension, diabetes, and being overweight and by inferior socioeconomic circumstances. These risk factors accounted for a substantial proportion of the geographic variance in incidence of stroke.
Functional MRI Detects Posterior Shifts in Primary Sensorimotor Cortex Activation After Stroke
Authors: Pineiro R. , Pendlebury S. , Johansen-Berg H. , Matthews P. M.
Published: June 2011

Background and Purpose
—Further recovery from stroke can occur late, long after the end of the apparent evolution of pathological changes. This observation and evidence obtained from functional imaging for altered patterns of activation after brain injury suggest that cortical reorganization may contribute to recovery. Here, we have tested for potentially adaptive reorganization in the primary sensorimotor cortex.

Methods
—We used functional MRI to study brain activation with dominant hand movement in right-handed healthy control subjects (n=20) and in patients after subcortical ischemic infarcts causing mild to moderate right hemiparesis (n=8). The numbers of pixels activated above threshold and the geometric centers of activation clusters were determined.

Results
—Although random-effects analysis identified some differences in activation maxima, similar regions of the brain were activated with sequential finger tapping in the patient and control groups. However, consistent with the heterogeneity in the locations, sizes, and times after the infarcts, patterns and magnitudes of activation showed some heterogeneity between patients. Nonetheless, for the group as a whole, there was a decreased motor cortex lateralization index (−0.1±0.7 in patients and 0.7±0.3 in control subjects,
P
=0.05). The geometric center of activation of the primary sensorimotor cortex activation cluster contralateral to the affected hand in patients was also shifted posteriorly (mean 12 mm,
P
<0.04) relative to that of the control subjects. To confirm the latter observation, the activation response with a simple hand-tapping task was examined in some of the subjects. With this task, there was also a trend (mean 10 mm,
P
=0.07) toward a more posterior activation in patients.

Conclusions
—These results confirm altered patterns of activation in the contralateral and ipsilateral primary sensorimotor cortices after recovery from strokes causing hemiparesis. These (and other changes) suggest that modulation of widely distributed parts of the cortical network for motor control may contribute to adaptations leading to functional recovery after stroke.
Attributable Risk of Common and Rare Determinants of Subarachnoid Hemorrhage
Authors: Ruigrok Ynte M. , Buskens Erik , Rinkel Gabriël J. E.
Published: June 2011

Background and Purpose
—Smoking, hypertension, alcohol consumption, autosomal dominant polycystic kidney disease (ADPKD), and positive family history for subarachnoid hemorrhage (SAH) are well-known risk factors for SAH. For effective prevention, knowledge about the contribution of these risk factors to the overall occurrence of SAH in the general population is pivotal. We therefore investigated the population attributable risks of the risk factors for SAH.

Methods
—We retrieved the relative risk and prevalence of established risk factors for SAH from the literature and calculated the population attributable risks of these risk factors.

Results
—Drinking alcohol 100 to 299 g/wk accounted for 11% of the cases of SAH, drinking alcohol ≥300 g/wk accounted for 21%, and smoking accounted for 20%. An additional 17% of the cases could be attributed to hypertension, 11% to a positive family history for SAH, and 0.3% to ADPKD.

Conclusions
—Screening and preventive treatment of patients with familial preponderance of SAH alone will cause a modest reduction of the incidence of SAH in the general population. Further reduction can be achieved by reducing the prevalence of the modifiable risk factors alcohol consumption, smoking, and hypertension.
A New Rating Scale for Age-Related White Matter Changes Applicable to MRI and CT
Authors: Wahlund L. O. , Barkhof F. , Fazekas F. , Bronge L. , Augustin M. , Sjögren M. , Wallin A. , Ader H. , Leys D. , Pantoni L. , Pasquier F. , Erkinjuntti T. , Scheltens P.
Published: June 2011

Background and Purpose
—MRI is more sensitive than CT for detection of age-related white matter changes (ARWMC). Most rating scales estimate the degree and distribution of ARWMC either on CT or on MRI, and they differ in many aspects. This makes it difficult to compare CT and MRI studies. To be able to study the evolution and possible effect of drug treatment on ARWMC in large patient samples, it is necessary to have a rating scale constructed for both MRI and CT. We have developed and evaluated a new scale and studied ARWMC in a large number of patients examined with both MRI and CT.

Methods
—Seventy-seven patients with ARWMC on either CT or MRI were recruited and a complementary examination (MRI or CT) performed. The patients came from 4 centers in Europe, and the scans were rated by 4 raters on 1 occasion with the new ARWMC rating scale. The interrater reliability was evaluated by using κ statistics. The degree and distribution of ARWMC in CT and MRI scans were compared in different brain areas.

Results
—Interrater reliability was good for MRI (κ=0.67) and moderate for CT (κ=0.48). MRI was superior in detection of small ARWMC, whereas larger lesions were detected equally well with both CT and MRI. In the parieto-occipital and infratentorial areas, MRI detected significantly more ARWMC than did CT. In the frontal area and basal ganglia, no differences between modalities were found. When a fluid-attenuated inversion recovery sequence was used, MRI detected significantly more lesions than CT in frontal and parieto-occipital areas. No differences were found in basal ganglia and infratentorial areas.

Conclusions
—We present a new ARWMC scale applicable to both CT and MRI that has almost equal sensitivity, except for certain regions. The interrater reliability was slightly better for MRI, as was the detectability of small lesions.
Rapid Differential Endogenous Plasminogen Activator Expression After Acute Middle Cerebral Artery Occlusion
Authors: Hosomi Naohisa , Lucero Jacinta , Heo Ji Hoe , Koziol James A. , Copeland Brian R. , del Zoppo Gregory J.
Published: June 2011

Background and Purpose
—During focal cerebral ischemia, the microvascular matrix (ECM), which participates in microvascular integrity, is degraded and lost when neurons are injured. Loss of microvascular basal lamina antigens coincides with rapid expression of select matrix metalloproteinases (MMPs). Plasminogen activators (PAs) may also play a role in ECM degradation by the generation of plasmin or by MMP activation.

Methods
—The endogenous expressions of tissue-type plasminogen activator (tPA), urokinase (uPA), and PA inhibitor-1 (PAI-1) were quantified in 10-μm frozen sections from ischemic and matched nonischemic basal ganglia and in the plasma of 34 male healthy nonhuman primates before and after middle cerebral artery occlusion (MCA:O).

Results
—Within the ischemic basal ganglia, tissue uPA activity and antigen increased significantly within 1 hour after MCA:O (2
P
<0.005). tPA activity transiently decreased 2 hours after MCA:O (2
P
=0.01) in concert with an increase in PAI-1 antigen (2
P
=0.001) but otherwise did not change. The transient decrease in free tPA antigen was marked by an increase in the tPA–PAI-1 complex (2
P
<0.001). No significant relations to neuronal injury or intracerebral hemorrhage were discerned.

Conclusions
—The rapid increase in endogenous PA activity is mainly due to significant increases in uPA, but not tPA, within the ischemic basal ganglia after MCA:O. This increase and an increase in PAI-1 coincided with latent MMP-2 generation and microvascular ECM degeneration but not neuronal injury.
Barriers to Acute Stroke Therapy and Stroke Prevention in Mexican Americans
Authors: Morgenstern Lewis B. , Steffen-Batey Lyn , Smith Melinda A. , Moyé Lemuel A.
Published: June 2011

Background and Purpose
—The purpose of this study was to identify specific targets to improve acute stroke treatment and stroke prevention in the Mexican American (MA) community.

Methods
—A professional, academic survey research team provided structured questions and elicited responses from 719 subjects identified by random-digit dialing in the biethnic community of Corpus Christi, Texas. This community of approximately 300 000 is approximately half MA and half non-Hispanic white (NHW). The cooperation rate for the survey was 58%.

Results
—MAs (n=357) were younger, less well educated, and had lower family income than NHWs (n=362,
P
=0.001). MAs had a higher prevalence of diabetes mellitus (
P
=0.001) but similar rates of hypertension, elevated cholesterol, and current tobacco use. MAs less commonly recognized that acute stroke therapy existed (
P
=0.029), were less likely to acknowledge a time window for acute stroke treatment (
P
=0.001), and were more reticent to say they would call 911 for stroke symptoms (
P
=0.01) than NHWs. MAs were significantly less able to recall stroke symptoms and risk factors than NHWs. Only approximately 20% of both groups identified stroke as the No. 1 cause of disability. MAs expressed less confidence in their ability to prevent stroke (
P
<0.001), more distrust in the medical establishment (
P
=0.007), and more concern that money impedes their seeking medical care (
P
<0.001).

Conclusions
—There are significant barriers to both acute stroke treatment and stroke prevention in MAs. This study identifies specific targets amenable for testing in an intervention project following confirmation by a methodology other than telephone survey.
Trends in Incidence and Case Fatality Rates of Aneurysmal Subarachnoid Hemorrhage in Izumo City, Japan, Between 1980–1989 and 1990–1998
Authors: Inagawa Tetsuji
Published: June 2011

Background and Purpose
—With aging of the population, the profile of subarachnoid hemorrhage (SAH) is likely to change; however, evaluation of long-term trends for incidence and case fatality rates of SAH is still limited.

Methods
—We compared the incidence and case fatality rates of aneurysmal SAH during the 9-year period 1990–1998 with those during the 10-year period 1980–1989 in Izumo City, Japan.

Results
—During 1980–1989 and 1990–1998, we diagnosed 170 and 188 patients as having aneurysmal SAH, respectively. The percentage of very elderly patients aged ≥80 years increased from 5% (8 patients) during 1980–1989 to 18% (33 patients) during 1990–1998 (
P
<0.001). The age-specific incidence rate of SAH has a tendency to increase with increasing age. The crude and the age- and sex-adjusted incidence rates using the 1995 population statistics for Japan were 21 and 23 per 100 000/y for all ages during 1980–1989 and 25 and 23 per 100 000/y during 1990–1998, respectively. The 3-month case fatality rate of patients aged ≤79 years decreased from 38% during 1980–1989 to 26% during 1990–1998 (
P
=0.021), whereas the case fatality rates in patients aged ≥80 years were very high (63% and 79%, respectively) regardless of study periods. Consequently, the overall case fatality rates for patients with SAH were similar for the 2 study periods (39% and 36%).

Conclusions
—The age- and sex-adjusted incidence rates of aneurysmal SAH were stable over the 19-year period since 1980 and, despite improvement of outcome in patients aged ≤79 years, the overall case fatality rate was not lower because the improvements were counterbalanced by increasing numbers of very elderly patients
Is Carotid Intima-Media Thickness Useful in Cardiovascular Disease Risk Assessment?
Authors: del Sol Antonio Iglesias , Moons Karel G.M. , Hollander Monika , Hofman Albert , Koudstaal Peter J. , Grobbee Diederick E. , Breteler Monique M.B. , Witteman Jacqueline C.M. , Bots Michiel L.
Published: June 2011

Background and Purpose
—We determined the contribution of common carotid intima-media thickness (IMT) in the prediction of future coronary heart disease and cerebrovascular disease when added to established risk factors.

Methods
—We used data from a nested case-control study comprising 374 subjects with either an incident stroke or a myocardial infarction and 1496 controls. All subjects were aged 55 years and older and participated in the Rotterdam Study. Mean follow-up was 4.2 years (range, 0.1 to 6.5 years). We evaluated which correlates of coronary heart disease and cerebrovascular disease contribute to the prediction of either a new incident myocardial infarction or a stroke. Logistic regression modeling and the area under the receiver operating characteristic curve (ROC area) were used to quantify the predictive value of the established risk factors and the added value of IMT.

Results
—The ROC area of a model with age and sex only was 0.65 (95% CI, 0.62 to 0.69). Independent risk factors were previous myocardial infarction and stroke, diabetes mellitus, smoking, systolic blood pressure, diastolic blood pressure, and total and HDL cholesterol levels. These risk factors increased the ROC area from 0.65 to 0.72 (95% CI, 0.69 to 0.75). This model correctly predicted 17% of all subjects with coronary heart disease and cerebrovascular disease. When common carotid IMT was added to the previous model, the ROC area increased to 0.75 (95% CI, 0.72 to 0.78). When only the IMT measurement was used, the ROC area was 0.71 (95% CI, 0.68 to 0.74), and 14% of all subjects were correctly predicted. There was no difference in ROC area when different measurement sites were used.

Conclusions
—Adding IMT to a risk function for coronary heart disease and cerebrovascular disease does not result in a substantial increase in the predictive value when used as a screening tool.
Perfusion Magnetic Resonance Imaging Maps in Hyperacute Stroke
Authors: Parsons Mark W. , Yang Qing , Barber P. Alan , Darby David G. , Desmond Patricia M. , Gerraty Richard P. , Tress Brian M. , Davis Stephen M.
Published: June 2011

Background and Purpose
—In ischemic stroke, perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) provide important pathophysiological information. A PWI>DWI mismatch pattern suggests the presence of salvageable tissue. However, improved methods for distinguishing PWI>DWI mismatch tissue that is critically hypoperfused from benign oligemia are required.

Methods
—We investigated the usefulness of maps of relative cerebral blood flow (rCBF), volume (rCBV), and mean transit time (rMTT) to predict transition to infarction in hyperacute (<6 hours) stroke patients with PWI>DWI mismatch patterns. Semiquantitative color-thresholded analysis was used to measure hypoperfusion volumes, including increasing color signal intensity thresholds of rMTT delay, which were compared with infarct expansion, outcome infarct size, and clinical status.

Results
—Acute rCBF lesion volume had the strongest correlation with final infarct size (
r
=0.91,
P
<0.001) and clinical outcome (
r
=0.67,
P
<0.01). There was a trend for acute rCBF>DWI mismatch volume to overestimate infarct expansion between the acute and outcome study (
P
=0.06). Infarct expansion was underestimated by acute rCBV>DWI mismatch (
P
<0.001). When rMTT lesions included tissue with moderately prolonged transit times (mean delay 4.3 seconds, signal intensity values 50% to 70%), infarct expansion was overestimated. In contrast, when rMTT lesions were restricted to more severely prolonged transit times (mean delay 6.1 seconds, signal intensity >70%), these regions progressed to infarction in all except 1 patient, but infarct expansion was underestimated (
P
<0.001).

Conclusions
—The acute rCBF lesion most accurately identified tissue in the PWI>DWI mismatch region at risk of infarction. Color-thresholded PWI maps show potential for use in an acute clinical setting to prospectively predict tissue outcome.
Assessing Wolf Motor Function Test as Outcome Measure for Research in Patients After Stroke
Authors: Wolf Steven L. , Catlin Pamela A. , Ellis Michael , Archer Audrey Link , Morgan Bryn , Piacentino Aimee
Published: June 2011

Background and Purpose
—The Wolf Motor Function Test (WMFT) is a new time-based method to evaluate upper extremity performance while providing insight into joint-specific and total limb movements. This study addresses selected psychometric attributes of the WMFT applied to a chronic stroke population.

Methods
—Nineteen individuals after stroke and with intact cognition and sitting balance were age- and sex-matched with 19 individuals without impairment. Subjects performed the WMFT and the upper extremity portion of the Fugl-Meyer Motor Assessment (FMA) on 2 occasions (12 to 16 days apart), with scoring performed independently by 2 random raters.

Results
—The WMFT and FMA demonstrated agreement (
P
<0.0001) between raters at each session. WMFT scores for the dominant and nondominant extremities of individuals without impairment were different (
P
≤0.05) from the more and less affected extremities of subjects after stroke. The FMA score for the more affected extremity of subjects after stroke was different (
P
≤0.05) from the dominant and nondominant extremities. However, the FMA score for the less affected upper extremity of individuals after stroke was not different (
P
>0.05) from the dominant and nondominant extremities of individuals without impairment. The WMFT and FMA scores were related (
P
<0.02) for the more affected extremity in individuals after stroke.

Conclusions
—The interrater reliability, construct validity, and criterion validity of the WMFT, as used in these subject samples, are supported.
Transgenic CuZn-Superoxide Dismutase Inhibits NO Synthase Induction in Experimental Subarachnoid Hemorrhage
Authors: Saito Atsushi , Kamii Hideyuki , Kato Ichiro , Takasawa Shin , Kondo Takeo , Chan Pak H. , Okamoto Hiroshi , Yoshimoto Takashi
Published: June 2011

Background and Purpose
—The expression of inducible NO synthase (iNOS) after experimental subarachnoid hemorrhage (SAH) has been postulated to play a critical role in the pathogenesis of SAH and subsequent cerebral vasospasm. The inhibitory effect of CuZn-superoxide dismutase (CuZn-SOD) on the induction of iNOS after SAH was examined by using transgenic mice overexpressing CuZn-SOD.

Methods
—SOD-transgenic mice and nontransgenic littermates were subjected to SAH by endovascular perforation of the left anterior cerebral artery. The iNOS mRNA expression after SAH was determined by reverse transcription–polymerase chain reaction, and the distribution of iNOS-positive cells was immunohistochemically examined. The nuclear expression of activated nuclear factor-κB, a major transcription factor of iNOS gene, was also immunohistochemically examined.

Results
—In nontransgenic mice, SAH-induced iNOS protein and mRNA expressions in the arteries of basal cistern as well as in the cerebral cortex were demonstrated by immunohistochemistry and reverse transcription–polymerase chain reaction. SAH-induced iNOS protein and mRNA expressions in those tissues were much reduced in SOD-transgenic mice compared with nontransgenic mice. Moreover, the nuclear expression of the activated form of nuclear factor-κB was immunohistochemically detected in the cerebral cortices of nontransgenic mice but not in those of SOD-transgenic mice.

Conclusions
—These results indicate that oxygen-derived free radicals, particularly superoxide, play an important role in the iNOS gene expression after SAH and provide a molecular basis for the protective role of SOD against vasospasm after SAH.
Vasospasm in Monkeys Resolves Because of Loss of and Encasement of Subarachnoid Blood Clot
Authors: Zhang Zhen-Du , Yamini Baktair , Komuro Taro , Ono Shigeki , Johns Lydia , Marton Linda S. , Weir Bryce , Macdonald R. Loch
Published: June 2011

Background and Purpose
—

We studied in monkeys why vasospasm resolves after subarachnoid hemorrhage (SAH).

Methods
—

Monkeys underwent angiography and right (n=17) or bilateral (n=8) SAH. Animals with bilateral SAH underwent angiography 1, 3, 5, and 7 days later. Animals with right SAH underwent angiography 7 days later. The clot was then not removed (n=5), removed and replaced with fresh clot (n=7), or removed and not replaced (n=5). At the same time on day 7, the removed clot (n=12) or fresh clot (n=5) was placed on the left side. Angiography was repeated every 2 days until day 14.

Results
—

SAH caused significant vasospasm on day 7 that resolved by day 14. Removal of clot on day 7 resulted in more rapid resolution of vasospasm. Placement of fresh clot onto arteries that had already been exposed to clot for 7 days produced vasospasm that persisted without resolving for an additional 7 days. Placement of 7-day-old clot from the right onto previously unexposed left arteries or of clot from blood removed from an animal 7 days after SAH caused significantly more rapid onset of vasospasm compared with de novo vasospasm. Microscopic examination of the clots showed they were surrounded by macrophages 7 days after SAH. Arterial compliance and contractility were reduced in relation to duration of the exposure of arteries to clot.

Conclusions
—

Vasospasm resolves because of loss of subarachnoid blood clot. We hypothesize that reduced spasmogen release from the clot contributes to resolution of vasospasm. There was no response in the cerebral arteries that rendered them less responsive to the subarachnoid clot.