bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxygen-Glucose Deprivation Induces Inducible Nitric Oxide Synthase and Nitrotyrosine Expression in Cerebral Endothelial Cells
Authors: Xu Jan , He Luming , Ahmed S. Hinan , Chen Sha-Wei , Goldberg Mark P. , Beckman Joseph S. , Hsu Chung Y.
Published: June 2011

Background and Purpose
—The cerebral endothelial cells (ECs) are a primary target of hypoxic or ischemic brain insults. EC damage may contribute to postischemic secondary injury. Massive production of NO after inducible NO synthase (iNOS) expression has been implicated in cell death. This study aimed to characterize bovine cerebral EC death in relation to iNOS expression after oxygen-glucose deprivation (OGD) in vitro.

Methods
—OGD in bovine cerebral ECs in culture was induced by deleting glucose in the medium and by incubating the cells in a temperature-controlled anaerobic chamber. The extent of cell death was assessed by trypan blue exclusion, MTT assay, and LDH release. ELISA, gel electrophoresis, and staining by terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling were used to examine DNA fragmentation. The expression of iNOS mRNA and protein was detected by reverse transcription–polymerase chain reaction and Western blotting, respectively. Nitrotyrosine expression was confirmed with Western blot analysis and immunostaining.

Results
—Bovine cerebral EC death was dependent on the duration of OGD and showed selected biochemical, morphological, and pharmacological features suggestive of apoptosis. OGD also induced the expression of iNOS mRNA and protein in bovine cerebral ECs. Increased expression of nitrotyrosine, the product formed by peroxynitrite reaction with proteins, was also detected after OGD. The involvement of iNOS in EC death was suggested by partial reduction of cell death by NO synthase inhibitors, including
l
-
N
G
-(1-iminoethyl)ornithine and nitro-
l
-arginine, and an NO scavenger, the Fe
2+
-
N
-methyl-
d
-glucamine dithiocarbamate complex.

Conclusions
—OGD-induced bovine cerebral EC death involves an apoptotic process. Induction of iNOS with subsequent peroxynitrite formation may contribute to bovine cerebral EC death caused by OGD.
Loss of Psychic Self-Activation After Paramedian Bithalamic Infarction
Authors: Engelborghs S. , Marien P. , Pickut B. A. , Verstraeten S. , De Deyn P. P.
Published: June 2011

Background and Purpose
—Loss of psychic self-activation has been described after bilateral lesions to the globus pallidus, striatum, and white matter of the frontal lobes, but it is a very rare sign of bithalamic lesions. The exact functional-anatomic mechanism underlying loss of psychic self-activation following bithalamic lesions remains to be elucidated.

Case Description
—We present clinical, neuropsychological, structural, and functional neuroimaging data of an 18-month follow-up period of a man with prominent loss of psychic self-activation after coronary arteriography. Except for memory decline, accompanying symptoms remained restricted to the acute phase. The neurobehavioral syndrome consisted mainly of apathy, indifference, poor motivation, and flattened affect, and this remained unchanged during the entire follow-up period. MRI showed a bithalamic infarction involving the nucleus medialis thalami bilaterally. Single-photon emission CT revealed a severe relative hypoperfusion of both thalami, a relative hypoperfusion of both nuclei caudati, and a relative hypoperfusion mesiofrontally.

Conclusions
—Single-photon emission CT data support the hypothesis that the neurobehavioral manifestations after bithalamic paramedian infarction are caused by disruption of the striatal-ventral pallidal-thalamic-frontomesial limbic loop. Probably, bilateral disruption at different levels of the striatal-ventral pallidal-thalamic-frontomesial loop may lead to a similar clinical picture consisting of loss of psychic self-activation.
Oxidative Stress in the Context of Acute Cerebrovascular Stroke
Authors: El Kossi Mohsen Muhammad Hussein , Zakhary Madeha Mahrous
Published: June 2011

Background and Purpose
—Free radical generation and consequent oxidative stress in thrombotic cerebrovascular stroke have a distinctive role in the pathogenesis of ischemic brain injury. One of the potential injurious effects of homocyst(e)ine in occlusive vascular diseases is free radical generation. In the current study, we investigated the status of oxidant stress in the acute phase of thrombotic cerebrovascular stroke and the possible role of homocyst(e)ine.

Methods
—We determined levels of plasma homocyst(e)ine, lipid peroxide, ascorbic acid, superoxide dismutase, and nitric oxide in 30 patients with thrombotic cerebrovascular stroke within 2 days of the onset of the attack as well as in 22 healthy volunteers of comparable age and gender.

Results
—Statistically significant elevation of homocyst(e)ine (
P
<0.001), lipid peroxide (
P
<0.001), and nitric oxide (
P
<0.001) plasma levels were observed in stroke patients compared with healthy controls. On the other hand, the antioxidant ascorbic acid plasma levels were significantly lower in the patient group compared with healthy control subjects (
P
<0.001). Meanwhile, superoxide dismutase plasma levels were not statistically different in either groups. The study also revealed a significant and strong positive correlation between homocyst(e)ine and lipid peroxide (
r
=0.85,
P
<0.001). Ascorbic acid plasma levels were significantly negatively correlated with both homocyst(e)ine (
r
=−0.875,
P
<0.001) and lipid peroxide (
r
=−0.576,
P
<0.001). The nitric oxide level was positively correlated with superoxide dismutase (
r
=0.396,
P
<0.05).

Conclusions
—We conclude that hyperhomocyst(e)inemia is a possible causal factor in free radical generation during the acute phase of thrombotic cerebrovascular stroke. Pharmacological intervention could potentially be beneficial in this setting and warrants further evaluation.
A Longitudinal Study of Collateral Flow Patterns in the Circle of Willis and the Ophthalmic Artery in Patients With a Symptomatic Internal Carotid Artery Occlusion
Authors: Rutgers D. R. , Klijn C. J. M. , Kappelle L. J. , van Huffelen A. C. , van der Grond J.
Published: June 2011

Background and Purpose
—The purpose of the present study was to assess whether the direction of flow via the circle of Willis and the ophthalmic artery (OphA) changed over time in patients with a symptomatic occlusion of the internal carotid artery (ICA) who did not experience recurrent cerebral ischemic symptoms.

Methods
—Sixty-two patients with a symptomatic ICA occlusion were investigated within 6 months after symptoms occurred. The investigations were repeated after 6 and 12 months. The directions of flow in the A1 segment and the posterior communicating artery (PCoA), both on the side of the symptomatic ICA occlusion, were assessed with the use of magnetic resonance angiography. The pattern of collateral flow via the circle of Willis was categorized as via the A1 segment only, via the PCoA only, via the A1 segment plus the PCoA, or no collateral flow via the circle of Willis. The direction of flow in the OphA was investigated with transcranial Doppler sonography. CO
2
reactivity was determined with transcranial Doppler sonography to investigate whether changes in flow patterns were accompanied by changes in cerebrovascular reactivity.

Results
—There were no statistically significant changes over time in the direction of blood flow in the A1 segment and the PCoA or in the pattern of collateral flow via the circle of Willis. On average, 72% of patients with a unilateral ICA occlusion (n=41) had willisian collateral flow compared with 37% of patients with a bilateral ICA occlusion (n=21;
P
<0.05). Patients with a unilateral ICA occlusion tended to a lower prevalence of reversed flow via the OphA over time. CO
2
reactivity did not change significantly in any patient group. In patients with a unilateral ICA occlusion, decreased CO
2
reactivity was associated with a higher prevalence of absent willisian collateral flow and a lower prevalence of collateral flow via the A1 segment plus the PCoA.

Conclusions
—The absence of recurrent cerebral ischemic symptoms in patients with a symptomatic ICA occlusion is not associated with an improvement in collateral flow via the circle of Willis or the OphA during 1.5-year follow-up.
White Matter Injury in Spinal Cord Ischemia
Authors: Kanellopoulos Georgios K. , Xu Xiao Ming , Hsu Chung Y. , Lu Xiaobin , Sundt Thoralf M. , Kouchoukos Nicholas T.
Published: June 2011

Background and Purpose
—Spinal cord ischemia is a serious complication of surgery of the aorta. NMDA receptor activation secondary to ischemia-induced release of glutamate is a major mechanism of neuronal death in gray matter. White matter injury after ischemia results in long-tract dysfunction and disability. The AMPA/kainate receptor mechanism has recently been implicated in white matter injury.

Methods
—We studied the effects of AMPA/kainate receptor blockade on ischemic white matter injury in a rat model of spinal cord ischemia.

Results
—Intrathecal administration of an AMPA/kainate antagonist, 6-nitro-7-sulfamoyl-(f)-quinoxaline-2,3-dione (NBQX), 1 hour before ischemia reduced locomotor deficit, based on the Basso-Beattie-Bresnahan scale (0=total paralysis; 21=normal) (sham: 21±0, n=3; saline: 3.7±4.5, n=7; NBQX: 12.7±7.0, n=7,
P
<0.05) 6 weeks after ischemia. Gray matter damage and neuronal loss in the ventral horn were evident after ischemia, but no difference was noted between the saline and NBQX groups. The extent of white matter injury was quantitatively assessed, based on axonal counts, and was significantly less in the NBQX as compared with the saline group in the ventral (sham: 1063±44/200×200 μm, n=3; saline: 556±104, n=7; NBQX: 883±103, n=7), ventrolateral (sham: 1060±135, n=3; saline: 411±66, n=7; NBQX: 676±122, n=7), and corticospinal tract (sham: 3391±219, n=3; saline: 318±23, n=7; NBQX: 588±103, n=7) in the white matter on day 42.

Conclusions
—Results indicate severe white matter injury in the spinal cord after transient ischemia. NBQX, an AMPA/kainate receptor antagonist, reduced ischemia-induced white matter injury and improved locomotor function.
Atherothrombotic Middle Cerebral Artery Territory Infarction
Authors: Min Wang K. , Park Kyoung K. , Kim Yong S. , Park Heui C. , Kim Jong Y. , Park Sung P. , Suh Chung K.
Published: June 2011

Background and Purpose
— MRI has superior capabilities for the detection of cerebral infarcts compared with CT. CT was used to locate infarcts in most previous studies of atherothrombotic middle cerebral artery (MCA) territory infarcts. Thus, there was a possibility of missing concomitant small infarcts. More accurate identification of topographic lesions in MCA territory with MRI may help to establish the pathogenesis of stroke. The present study determines topographic patterns, distribution of vascular lesions, and probable mechanisms.

Methods
—Forty-two patients with MCA territory infarcts on routine MRI and no major cause of cardioembolism were studied with conventional angiography or MR angiography.

Results
—The topographic patterns seen on MRI were subdivided into 4 groups: cortical border-zone infarcts (n=6), pial territory infarcts without insular infarct (n=3), pial territory infarcts with insular infarct (n=14), and large subcortical infarcts (n=19). Of 6 patients with cortical border-zone infarcts, 4 had concomitant small cortical or subcortical multiple lesions. Angiography showed intrinsic MCA disease in 4 patients. Of 3 patients with pial territory infarcts without insular infarct, 2 also had small multiple centrum ovale lesions. All had intrinsic MCA disease. Pial territory infarcts with partial or whole insular lesions were present in 10 and 4 patients, respectively. Five patients had additional multiple cortical or subcortical lesions. Ten patients had intrinsic MCA disease. Of the 19 patients with large subcortical infarcts, 12 had centrum ovale infarcts, and 4 had both basal ganglia and centrum ovale lesions. Ten had concomitant small cortical or subcortical lesions. Six patients had intrinsic MCA disease.

Conclusions
—Similar vascular lesions induce different topographic patterns in MCA territory infarction, which are related to individual vascular variability, degree of primary and secondary collateralization, and pathogenesis of infarcts. Our study indicates that concomitant small cortical or subcortical lesions are also commonly associated findings in diverse patterns of MCA territory infarction, which can mostly be explained by probable embolic mechanism.
Influence of Socioeconomic Circumstances in Early and Later Life on Stroke Risk Among Men in a Scottish Cohort Study
Authors: Hart Carole L. , Hole David J. , Smith George Davey
Published: June 2011

Background and Purpose
—The purpose of the study was to investigate stroke risk by socioeconomic measures.

Methods
—The analysis was based on a large cohort study of 5765 working men, from 27 workplaces in Scotland, who were screened between 1970 and 1973. Stroke was defined as having a hospital admission with a main diagnosis of stroke or dying of stroke in the 25-year follow-up period.

Results
—There were 416 men who had a stroke. Men with manual occupations when screened, on first entering the workforce, men with manual occupations, and men whose fathers had manual occupations had significantly higher rates of stroke than men in the nonmanual categories. Men who left full-time education at age 16 years or under also had significantly higher rates of stroke. Men living in more deprived areas had higher rates of stroke, but the rates were not statistically significant. The most marked difference was in relation to father’s social class, and although adjusting for risk factors for stroke attenuated the relative rates, men whose fathers were in manual social classes had higher relative rates of stroke than men whose fathers were in nonmanual classes (adjusted relative rate for father’s social class III manual was 1.37 [95% CI 1.03 to 1.81] and for father’s social class IV or V was 1.46 [1.09 to 1.96]). Men who were upwardly mobile (father’s social class manual, own social class nonmanual) had a rate of stroke similar to that of stable manual men.

Conclusions
—Poorer socioeconomic circumstance was associated with greater stroke risk, with adverse early-life circumstances of particular importance.
Thrombin Reduces Cerebral Arterial Contractions Caused by Cerebrospinal Fluid From Patients With Subarachnoid Hemorrhage
Authors: Borsody Mark K. , DeGiovanni Gina M. , Marton Linda S. , Macdonald Robert L. , Weir Bryce
Published: June 2011

Background and Purpose
—We observed that the second application of cerebrospinal fluid (CSF) from subarachnoid hemorrhage (SAH) patients onto cerebral arterial segments in vitro produces a greater contraction than does the initial application. It was hypothesized that the difference between the first and second applications of SAH CSF was due to the activity of thrombin.

Methods
—Canine vertebrobasilar artery was removed under general anesthesia, cut into rings, and suspended in tissue culture baths so as to measure isometric tension. CSF was taken from patients 1 to 3 days after SAH via ventricular drains. CSF was administered in 10
−
5
to 10
−
1
dilutions. The thrombin antagonist hirudin (5 U) was administered before CSF in some experiments. The arterial tension response to pure oxyhemoglobin (10
−
4
to 3.2 g/dL) and thrombin (10
−
4
to 3.2 U/mL), administered alone or in combination, was also examined.

Results
—Hirudin increased arterial tension generated on the initial application of SAH CSF but had no effect on the tension generated by the second application of the SAH CSF, suggesting that thrombin limits the tension generated by vasoconstrictive agents in the CSF. Thrombin and pure oxyhemoglobin administered together produced less tension than that generated in response to oxyhemoglobin administered alone; no additive response was observed by coadministering the 2 vasoconstrictive agents.

Conclusions
—In the presence of oxyhemoglobin, thrombin acts to reduce cerebral arterial tension. This interaction between thrombin and hemoglobin may account for the observation that the second application of CSF from SAH patients onto cerebral arterial segments in vitro produces a greater contraction than does the initial application.
Effect of Perindopril on Cerebral and Renal Perfusion in Stroke Patients With Carotid Disease
Authors: Walters M. R. , Bolster A. , Dyker A. G. , Lees K. R.
Published: June 2011

Background and Purpose
—The purpose of this study was to investigate the effect of the angiotensin-converting enzyme inhibitor perindopril on mean arterial blood pressure (MABP), cerebral blood flow (CBF), and glomerular filtration rate in hypertensive stroke patients with moderate to severe internal carotid artery (ICA) disease or ICA occlusion.

Methods
—Twenty-four nonacute ischemic stroke patients who had MABP readings >100 mm Hg and moderate to severe ICA stenosis or occlusion were randomized to receive perindopril 4 mg daily or placebo for 14 days. MABP, ICA flow, and both middle cerebral artery (MCA) velocity and resistance index were measured before dose, at 5 time points over the subsequent 24 hours, and finally at 2 weeks. Brain hexamethyl propylene amine oxide single photon emission computed tomography scans were performed before drug administration and at time of peak drug effect (6 to 8 hours) after the first dose. Glomerular filtration rate was measured with
51
Cr EDTA before medication and at 14 days.

Results
—A placebo-corrected BP fall of 17/10 mm Hg was seen (
P
=0.017), which was maximal at 5.5 hours. No significant change in ICA flow or MCA velocity was seen between groups. No significant change in hemispheric CBF was seen. The mean change from baseline in the treated group was −0.79 mL · 100 g
−1
· min
−1
(95% confidence interval [CI], 1.65 to −3.23); mean change in the placebo group was −1.9 mL · 100 g
−1
· min
−1
(95%CI, 3.02 to −6.92). Peri-infarct CBF was similarly unaffected. One of the treated patients developed transient acute renal impairment and was withdrawn from the study on day 4.

Conclusions
—Perindopril lowers BP without lowering CBF in hypertensive stroke patients with moderate to severe ICA stenosis or occlusion; monitoring of this patient population for the complications of renal artery stenosis should be considered.
Altered Expression of P
2
Receptor mRNAs in the Basilar Artery in a Rat Double Hemorrhage Model
Authors: Carpenter Robin C. , Miao Liyan , Miyagi Yasushi , Bengten Eva , Zhang John H.
Published: June 2011

Background and Purpose
—Extracellular ATP might induce cerebral vasospasm after subarachnoid hemorrhage through P
2
receptor. To investigate the roles of P
2
receptor subtypes in vasospasm, we examined the changes in mRNA expression of P
2
receptor subtypes in basilar arteries from double cisternal blood injection rat models.

Methods
—One hundred male Sprague-Dawley rats, each weighing 350 to 400 g, were divided into 2 groups of 50. In the first group (n=50), the autologous arterial blood (0.2 to 0.3 mL) was injected into the cisterna magna on days 0 and 2. The rats were killed on day 3, 5, or 7 (n=10 in each group). In the sham group (n=10), the rats were injected with saline (0.3 mL) instead of blood. Ten rats were killed without blood or saline injection and served as control. The basilar arteries from rats in each group were used for reverse transcription and polymerase chain reaction. In another group of 50 rats, the same experiment was conducted, and the basilar arteries were collected for transmission electron microscopic study.

Results
—In the subarachnoid hemorrhage groups, transmission electron microscopy showed the reduction in vessel perimeter on days 5 and 7 to be approximately 30% to 40%. The P
2X1
mRNA level was significantly decreased on day 3 and recovered on days 5 and 7. The P
2Y1
mRNA level was transiently increased on day 5, and the P
2Y2
mRNA level was elevated from day 5 to day 7 (
P
<0.05).

Conclusions
—The differential expression of the P
2
receptors indicates that P
2X1
subtype might not play an important role in vasospasm. The upregulation of P
2Y1
and P
2Y2
receptors might enable ATP to produce contraction at low levels of concentration.
Acute and Long-Term Increase in Fracture Risk After Hospitalization for Stroke
Authors: Kanis John , Oden Anders , Johnell Olof
Published: June 2011

Background and Purpose
—The aims of this study were to determine the magnitude of the increase in fracture risk after hospitalization for stroke, and in particular to determine the time course of this risk.

Methods
—The records of the Swedish register of patients admitted during 1987–1996 were examined to identify all patients who were admitted to the hospital for stroke. Patients were followed for subsequent hospitalizations for hip and all fractures combined. We analyzed 16.3 million hospitalizations, from which 273 288 individuals with stroke were identified. A Poisson model was used to determine the absolute risk of subsequent fractures and the risk compared with that of the general population.

Results
—After hospitalization for stroke, there was a >7-fold increase in fracture risk, including that for hip fracture within the first year after hospitalization for stroke. Thereafter, fracture risk declined toward, but did not attain, the baseline risk except in men and women aged ≥80 years.

Conclusions
—The high incidence of new fractures within the first year of hospitalization for stroke suggests that such patients should be preferentially targeted for treatment. It is possible that short courses of treatment at the time of stroke would provide important therapeutic dividends.
Acupuncture and Transcutaneous Nerve Stimulation in Stroke Rehabilitation
Authors: Johansson Barbro B. , Haker Eva , von Arbin Magnus , Britton Mona , Långström Göran , Terént Andreas , Ursing Dag , Asplund Kjell
Published: June 2011

Background and Purpose
—In small trials with control groups that receive no intervention, acupuncture has been reported to improve functional outcome after stroke. We studied effects of acupuncture and transcutaneous electrical nerve stimulation on functional outcome and quality of life after stroke versus a control group that received subliminal electrostimulation.

Methods
—In a multicenter randomized controlled trial involving 7 university and district hospitals in Sweden, 150 patients with moderate or severe functional impairment were included. At days 5 to 10 after acute stroke, patients were randomized to 1 of 3 intervention groups: (a) acupuncture, including electroacupuncture; (b) sensory stimulation with high-intensity, low-frequency transcutaneous electrical nerve stimulation that induces muscle contractions; and (c) low-intensity (subliminal) high-frequency electrostimulation (control group). A total of 20 treatment sessions were performed over a 10-week period. Outcome variables included motor function, activities of daily living function, walking ability, social activities, and life satisfaction at 3-month and 1-year follow-up.

Results
—At baseline, patients in each group were closely similar in all important prognostic variables. At 3-month and 1-year follow-ups, no clinically important or statistically significant differences were observed between groups for any of the outcome variables. The 3 treatment modalities were all conducted without major adverse effects.

Conclusions
—When compared with a control group that received subliminal electrostimulation, treatment during the subacute phase of stroke with acupuncture or transcutaneous electrical nerve stimulation with muscle contractions had no beneficial effects on functional outcome or life satisfaction.
Electrophysiological Properties of CA1 Neurons Protected by Postischemic Hypothermia in Gerbils
Authors: Dong H. , Moody-Corbett F. , Colbourne F. , Pittman Q. , Corbett D.
Published: June 2011

Background and Purpose
—Recent studies show that prolonged (eg, 24-hour) postischemic hypothermia confers lasting histological and behavioral protection against severe global cerebral ischemia. However, functional abnormalities may be compensated for by undamaged brain regions and thus not detected by behavioral tests. To determine whether hypothermia preserves CA1 functional integrity, we measured synaptic and membrane properties of CA1 neurons in ischemic gerbils treated with postischemic hypothermia.

Methods
—Gerbils were subjected to 5 minutes of forebrain ischemia and were either left untreated or exposed to 2 days of hypothermia (32°C for 24 hours and then 34°C for 24 hours). Sham animals were operated on but not made ischemic, then either allowed to recover at room temperature or subjected to hypothermia for 2 days. Approximately 5 weeks after ischemia or sham surgery, patch-clamp recordings were obtained from the CA1 region of hippocampal slices.

Results
—There was approximately 95% CA1 cell loss in untreated ischemic animals, whereas ischemic gerbils treated with hypothermia had cell counts similar to sham animals. Resting membrane potential, action potential amplitude and duration, input resistance, and synaptic currents evoked by Schaffer collateral stimulation were similar between pyramidal cells obtained from ischemic gerbils treated with hypothermia and sham-operated animals (
P
>0.05).

Conclusions
—These data demonstrate that postischemic hypothermia preserves the measured electrophysiological properties of CA1 neurons in the absence of any apparent functional abnormalities. This study provides further support for the use of hypothermia as a treatment for cerebral ischemia.
Acute Stroke Management in the Local General Hospital
Authors: Handschu René , Garling Andreas , Heuschmann Peter Ulrich , Kolominsky-Rabas Peter L. , Erbguth Frank , Neundörfer Bernhard
Published: June 2011

Background and Purpose
—The majority of stroke patients are treated in local general hospitals. Despite this fact, little is known about stroke care in these institutions. We sought to investigate the status quo of acute stroke management in nonspecialized facilities with limited equipment and resources.

Methods
—Four general hospitals located in smaller cities of a rural area in Germany participated in this study. The 4 hospitals were similar in structure and technical equipment; none had a CT scanner in-house. We reviewed the medical records of every stroke patient hospitalized in 1 of the 4 hospitals within a period of 8 weeks within 1 year.

Results
—We collected data of a total of 95 patients at all 4 hospitals. The frequency of diagnostic tests was low: at least 1 CT scan was obtained in only 36.8% of all cases, whereas diagnostic methods available in-house were used more frequently, such as Doppler ultrasound (49.0%), echocardiography (42.3%), and 24-hour ECG registration (48.4%). Each hospital had a different therapeutic approach. Main therapeutic options were the use of pentoxyfilline (0% to 90.5%), osmodiuretics (0% to 90%), piracetam (0% to 93.3%), and hydroxyethylstarch (4.8% to 30%). Medication for long-term secondary prevention was given to 69.8% of all patients.

Conclusions
—This study provides one of the few data samples reflecting stroke care in smaller general hospitals. The findings demonstrate a partially suboptimal level of care in these institutions. To achieve future improvements, extended human and technical resources as well as research for stroke care should not be restricted to academic stroke centers.
Acoustic Shadowing on B-Mode Ultrasound of the Carotid Artery Predicts Ischemic Stroke
Authors: Hunt Kelly J. , Evans Greg W. , Folsom Aaron R. , Sharrett A. Richey , Chambless Lloyd E. , Tegeler Charles H. , Heiss Gerardo
Published: June 2011

Background and Purpose
—We examined the relationship of carotid artery lesions (CALs), with and without acoustic shadowing (AS), to incident ischemic stroke events in the Atherosclerosis Risk in Communities study cohort.

Methods
—The study population consisted of 13 123 men and women aged 45 to 64 years, and free of stroke, examined during 1986–1989. Over an average follow-up time of 8.0 years, 226 incident ischemic stroke cases (thromboembolic brain infarctions) were identified and classified by a standardized protocol. Three levels of exposure were defined on the basis of the presence of B-mode ultrasound–detected CALs and AS in a 3-cm segment of the carotid arteries centered at the bifurcation.

Results
—The hazard ratio for ischemic stroke adjusted for age, ethnicity, and study site for women with a CAL without AS, compared with those without a CAL, was 1.92 (95% CI, 1.23, 3.01), and the hazard ratio comparing those with a CAL with AS with those without a CAL was 4.01 (95% CI, 2.28, 7.06). The corresponding hazard ratios for men were 1.99 (95% CI, 1.36, 2.91) and 2.23 (95% CI, 1.32, 3.79). Although adjustment for diabetes, hypertension medication, systolic blood pressure, left ventricular hypertrophy score, fibrinogen, von Willebrand factor antigen, and smoking status attenuated these associations somewhat, when compared with no evidence of CALs, CALs with AS remained statistically significant predictors of ischemic stroke in women, while CALs without AS were predictive of ischemic stroke in men.

Conclusions
—B-mode ultrasound–detected CALs and AS serve as markers of atherosclerosis and thus are predictive of ischemic stroke.
Status Epilepticus After Stroke
Authors: Velioğlu Sibel K. , Özmenoğlu Mehmet , Boz Cavit , Alioğlu Zekeriya
Published: June 2011

Background and Purpose
—The main objective of our study was to determine the risk and predictive factors of status epilepticus (SE) after stroke.

Methods
—From 1988 to 2000, 1174 patients were admitted to the Department of Neurology at the Karadeniz Technical University Farabi Hospital with first-time strokes. Of these, 180 patients had poststroke first-time seizures (PFSs). We followed these 180 PFS patients for an average of 3.7 years or until death to determine the occurrence rate of SE. By comparing these data with those of PFS patients without SE, we investigated whether there were significant differences.

Results
—A total of 17 of the 180 PFS patients (9%) had SE. There was no relationship between the occurrence of SE and stroke risk factors, stroke type (ischemic or hemorrhagic stroke), stroke topography and cause, cortical involvement, size of lesion, seizure type, or electroencephalographic findings. SE occurred more frequently among patients with a higher disability rating (Rankin scale >3; odds ratio, 4.36). Recurrent SE was identified in 5 of 17 patients with SE. In all 5 of these patients, the first episode of SE occurred within the first 7 days after stroke (early-onset SE). Statistical analysis demonstrated that early-onset SE was associated with a higher risk for SE recurrence (
P
=0.003) and a higher mortality rate (
P
=0.04).

Conclusions
—SE was not associated with a higher mortality rate but with higher functional disability. We also found that early-onset SE (within the first 7 days after stroke) was associated with a higher risk for SE recurrence and a higher mortality rate than late-onset SE (after 7 days after stroke).
Measurement of Vasomotor Reserve in the Transcranial Doppler-CO
2
Test Using an Ultrasound Contrast Agent (Levovist)
Authors: Rohrberg Matthias , Brodhun Rudolf
Published: June 2011

Background and Purpose
—Determination of vasomotor reserve (VMR) with the transcranial Doppler-CO
2
(TCD-CO
2
) test is used to assess the risk of impending cerebral ischemia in patients with high-grade stenosis or occlusion of the internal carotid artery. In patients with a poor temporal window, however, this examination is limited. The aim of this study therefore was to examine whether the use of an ultrasound contrast agent (USCA) influences the results of the TCD-CO
2
test.

Methods
—In the first part of the study, 6 control subjects and 20 patients were examined with the TCD-CO
2
test. The VMR was determined first without the application of a contrast agent and then with continuous infusion of an USCA (Levovist, 300 mg/mL, 1 mL/min). In the second part of the study, 2 tests without USCA were performed in each of 13 patients and 2 tests with USCA infusion were performed in each of 12 patients. Statistical analysis included differences between the VMR determined with the 2 comparative measurements (ΔVMR), the mean (MΔ
VMR
), and SD.

Results
—Based on the mean difference, the TCD-CO
2
test produced the same results with and without USCA (MΔ
VMR
1.8%), although the differences showed a wide distribution (2 SDs, ±20.7%). Similar spreads were seen in repeated determinations of VMR in the same patient without USCA (2 SDs, ±20.0%), whereas the distribution under continuous USCA infusion was considerably smaller (2 SDs, ±8.2%).

Conclusions
—The TCD-CO
2
test can be performed with continuous infusion of an USCA without influencing the results. Even with a good temporal window, the results of the TCD-CO
2
test show better reproducibility and thus better reliability if an USCA is used.
Trends in Acute Ischemic Stroke Trials Through the 20th Century
Authors: Kidwell Chelsea S. , Liebeskind David S. , Starkman Sidney , Saver Jeffrey L.
Published: June 2011

Background and Purpose
—The advent of controlled clinical trials revolutionized clinical medicine over the course of the 20th century. The objective of this study was to quantitatively characterize developments in clinical trial methodology over time in the field of acute ischemic stroke.

Methods
—All controlled trials targeting acute ischemic stroke with a final report in English were identified through MEDLINE and international trial registries. Data regarding trial design, implementation, and results were extracted. A formal 100-point scale was used to rate trial quality.

Results
—A total of 178 controlled acute stroke trials were identified, encompassing 73 949 patients. Eighty-eight trials involved neuroprotective agents, 59 rheological/antithrombotic agents, 26 agents with both neuroprotective and rheological/antithrombotic effects, and 5 a nonpharmacological intervention. Only 3 trials met conventional criteria for a positive outcome. Between the 1950s and 1990s, the number of trials per decade increased from 3 to 99, and mean trial sample size increased from 38 (median, 26) to 661 (median, 113). During 1980–1999, median time window allowed for enrollment decreased per half decade from 48 to 12 hours. Reported pharmaceutical sponsorship increased substantially over time, from 38% before 1970 to 68% in the 1990s. Trial quality improved substantially from a median score of 12 in the 1950s to 72 in the 1990s.

Conclusions
—Accelerating trends in acute stroke controlled trials include growth in number, sample size, and quality, and reduction in entry time window. These changes reflect an increased understanding of the pathophysiology of acute stroke, the imperative for treatment initiation within a critical time window, and more sophisticated trial design.
Early Decrease in DNA Repair Proteins, Ku70 and Ku86, and Subsequent DNA Fragmentation After Transient Focal Cerebral Ischemia in Mice
Authors: Kim Gyung W. , Noshita Nobuo , Sugawara Taku , Chan Pak H.
Published: June 2011

Background and Purpose
—Ku70 and Ku86, multifunctional DNA repair proteins, bind to broken DNA ends, including double-strand breaks, and trigger a DNA repair pathway. To investigate the involvement of these proteins in DNA fragmentation after ischemia/reperfusion, Ku protein expression was examined before and after transient focal cerebral ischemia (FCI) in mice.

Methods
—Adult male CD-1 mice were subjected to 60 minutes of FCI by intraluminal suture blockade of the middle cerebral artery. Ku protein expression was studied by immunohistochemistry and Western blot analysis. DNA fragmentation was evaluated by gel electrophoresis and terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling (TUNEL). The spatial relationship between Ku expression and DNA fragmentation was examined by double labeling with Ku and TUNEL after reperfusion.

Results
—Immunohistochemistry showed constitutive expression of Ku proteins in control brains. The number of Ku-expressing cells was decreased in the entire middle cerebral artery territory as early as 4 hours after reperfusion and remained reduced until 24 hours. Western blot analyses confirmed the significant reduction of these proteins (59.4% and 57.7% reduction in optical density at 4 hours of reperfusion from the normal level of Ku70 and Ku86 bands, respectively;
P
<0.001). DNA gel electrophoresis demonstrated DNA laddering 24 hours after reperfusion, but not at 4 hours. Double staining with Ku and TUNEL showed a concomitant loss of Ku immunoreactivity and TUNEL-positive staining.

Conclusions
—These results suggest that the early reduction of Ku proteins and the loss of defense against DNA damage may underlie the mechanism of DNA fragmentation after FCI.
Dietary Potassium Intake and Risk of Stroke in US Men and Women
Authors: Bazzano Lydia A. , He Jiang , Ogden Lorraine G. , Loria Catherine , Vupputuri Suma , Myers Leann , Whelton Paul K.
Published: June 2011

Background and Purpose
—The few prospective studies that have explored the association between dietary intake of potassium and risk of stroke have reported inconsistent findings. This study examines the relationship between dietary potassium intake and the risk of stroke in a representative sample of the US general population.

Methods
—Study participants included 9805 US men and women who participated in the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-Up Study. Dietary potassium and total energy intake were estimated at baseline by using a 24-hour dietary recall. Incidence data for stroke and coronary heart disease were obtained from medical records and death certificates.

Results
—Over an average of 19 years of follow up, 927 stroke events and 1847 coronary heart disease events were documented. Overall, stroke hazard was significantly different among quartiles of potassium intake (likelihood ratio
P
=0.03); however, a test of linear trend across quartiles did not reach a customary level of statistical significance (
P
=0.14). Participants consuming a low potassium diet at baseline (<34.6 mmol potassium per day) experienced a 28% higher hazard of stroke (hazard ratio 1.28, 95% CI 1.11 to 1.47;
P
<0.001) than other participants, after adjustment for established cardiovascular disease risk factors.

Conclusions
—These findings suggest that low dietary potassium intake is associated with an increased risk of stroke. However, the possibility that the association is due to residual confounding cannot be entirely ruled out in this observational study.
Polymorphism of the Lipoprotein Lipase Gene and Risk of Atherothrombotic Cerebral Infarction in the Japanese
Authors: Shimo-Nakanishi Yumi , Urabe Takao , Hattori Nobutaka , Watanabe Yoshiro , Nagao Takehiko , Yokochi Masayuki , Hamamoto Makoto , Mizuno Yoshikuni
Published: June 2011

Background and Purpose
—Lipid and lipoprotein abnormalities have been implicated in the pathogenesis of ischemic cerebrovascular disease and atherosclerosis. Lipoprotein lipase (LPL) plays an important role in plasma lipoprotein metabolism. Several studies have recently reported the presence of a relationship between Ser447Stop mutation of LPL and coronary artery disease. Other polymorphisms (
Hin
dIII and
Pvu
II) of the LPL gene have already been shown to correlate significantly with dyslipidemia. We investigated whether these polymorphisms are associated with increased risk of ischemic cerebrovascular disease (CVD).

Methods
—We recruited 177 CVD patients (atherothrombotic infarction, n=71; cardioembolic infarction, n=30; lacunar infarction, n=76) and 177 healthy control subjects. Subjects were genotyped for the Ser447Stop mutation and for
Hin
dIII/
Pvu
II restriction fragment length polymorphisms of the LPL gene, and the findings were investigated for associations with the clinical subtypes of CVD and with lipid levels.

Results
—The Ser447Stop mutation correlated significantly with CVD (0.107 versus 0.158;
P
=0.035). For the
CG+GG
versus
CC
genotype, the odds ratio between control subjects and CVD patients with atherothrombotic infarction was 0.42 (95% CI, 0.18 to 0.99) (
P
=0.046). Serum HDL cholesterol and triglyceride levels did not correlate significantly with the Ser447Stop genotype.
Hin
dIII polymorphism correlated significantly with CVD (0.234 versus 0.169;
P
=0.031), but the frequency of
Pvu
II polymorphism was not significantly different between groups.

Conclusions
—Our results suggest that the Ser447Stop mutation of the LPL gene is a novel genetic marker for low risk of atherothrombotic cerebral infarction.
Broad-Spectrum and Selective Serine Protease Inhibitors Prevent Expression of Platelet-Derived Growth Factor–BB and Cerebral Vasospasm After Subarachnoid Hemorrhage
Authors: Zhang Z. , Nagata I. , Kikuchi H. , Xue J-H. , Sakai N. , Sakai H. , Yanamoto H.
Published: June 2011

Background and Purpose
—Plasma serine protease cascade, including the complement system and thrombin, is activated in the subarachnoid space during the acute phase after subarachnoid hemorrhage (SAH). To examine the effect of protease cascade–based inflammation and subsequent vascular repair in the development of cerebral vasospasm, we examined the effect of 2 synthetic serine protease inhibitors—FUT-175, an inhibitor of thrombin and the complement system, and argatroban, a selective inhibitor of thrombin—on the development of cerebral vasospasm in a rabbit SAH model.

Methods
—One hundred Japanese White male rabbits were used in the study. The SAH was simulated by a single injection of autologous arterial blood into the cisterna magna. To evaluate the development of cerebral vasospasm, the caliber of the basilar artery was measured on x-ray film before and at 2 days after SAH. Nine groups of rabbits (n=6 each) were treated with continuous intravenous injection of FUT-175 (2.5, 5, 10, or 20 mg/d), argatroban (1.25, 2.5, or 5 mg/d), or the same amount of saline (vehicle) for 48 hours, starting 40 minutes after SAH. Two days after SAH, the expression of homodimer of platelet-derived growth factor–BB (PDGF-BB) in the basilar artery was examined with immunohistochemical techniques. In 20 normal rabbits, 5 μg of recombinant PDGF-BB or vehicle was injected into the cisterna magna, and the basilar arteries were examined on angiograms for 48 hours.

Results
—Significant differences were observed in the caliber of the basilar arteries between the vehicle group and the groups with the 3 larger doses of FUT-175 (vehicle, 52±5.0%; 5 mg, 79±5.7%; 10 mg, 80±2.5%; 20 mg, 80±3.7%) and between the vehicle group and the groups with the 2 larger doses of argatroban (vehicle, 52±6.4%; 2.5 mg, 81±9.0%; 5 mg, 85±4.1%) (
P
<0.05). In the histological examination, administration of effective doses of FUT-175 or argatroban suppressed the expression of PDGF-BB in the endothelial and medial smooth muscle cell layers. Exogenous PDGF-BB caused delayed and prolonged vasoconstriction on normal basilar arteries.

Conclusions
—Activation of the serine protease cascade and/or thrombin after SAH was demonstrated to play an essential role in the development of cerebral vasospasm. The expression of PDGF-BB–like protein in the arterial walls correlated with the development of cerebral vasospasm. Elevated PDGF-BB level in the subarachnoid space was found to induce delayed and chronic vasoconstriction.
Incidence of the Major Stroke Subtypes
Authors: Thrift Amanda G. , Dewey Helen M. , Macdonell Richard A.L. , McNeil John J. , Donnan Geoffrey A.
Published: June 2011

Background and Purpose

—

Population-based stroke incidence studies are the only accurate way to determine the number of strokes that occur in a given society. Because the major stroke subtypes have different patterns of incidence and outcome, information on the natural history of stroke subtypes is essential. The purpose of the present study was to determine the incidence and case-fatality rate of the major stroke subtypes in a geographically defined region of Melbourne, Australia.

Methods

—

All suspected strokes that occurred among 133 816 residents of suburbs north and east of Melbourne, Australia, during a 12-month period of 1996 and 1997 were identified and assessed. Multiple overlapping sources were used to ascertain cases, and standard criteria for stroke and case-fatality were used. Stroke subtypes were defined by CT, MRI, and autopsy.

Results

—

Three hundred eighty-one strokes occurred among 353 persons during the study period, with 276 (72%) being first-ever-in-a-lifetime strokes. Of these, 72.5% (95% CI 67.2% to 77.7%) were cerebral infarction, 14.5% (95% CI 10.3% to 18.6%) were intracerebral hemorrhage, 4.3% (95% CI 1.9% to 6.8%) were subarachnoid hemorrhage, and 8.7% (95% CI 5.4% to 12.0%) were stroke of undetermined type. The 28-day case-fatality rate was 12% (95% CI 7% to 16%) for cerebral infarction, 45% (95% CI 30% to 60%) for intracerebral hemorrhage, 50% (95% CI 22% to 78%) for subarachnoid hemorrhage, and 38% (95% CI 18% to 57%) for stroke of undetermined type.

Conclusions

—

The overall distribution of stroke subtypes and 28-day case-fatality rates are not significantly different from those of most European countries or the United States. There may, however, be some differences in the incidence of subtypes within Australia.
Changes in Stroke Mortality Rates for 1950 to 1997
Authors: Liu Longjian , Ikeda Katsumi , Yamori Yukio
Published: June 2011

Background and Purpose

—

Stroke is the second leading cause of death in Japan. We sought to examine changes in stroke mortality rates by age, sex, and birth cohorts from 1950 to 1997.

Methods

—

The numbers of deaths from stroke and the population by age and sex in subjects aged 55 to 79 years between 1950 and 1997 were obtained from national vital statistics. Poisson regression analyses for annual percentage changes were used to explore these trends.

Results

—

Stroke mortality rates decreased since the mid-1960s for both men and women. Four periods of the decline are identified. In the first period (1950 to 1964), the age-adjusted annual percent changes averaged 0.9% for men (
P
<0.05) and −0.6% for women (
P
>0.05). In the second period (1965 to 1974), the annual change averaged −5.0% for men and −5.2% for women (both
P
<0.01). In the third period (1975 to 1989), the annual change averaged −8.6% for men and −8.7% for women (both
P
<0.01). In the fourth period (1990 to 1997), the annual change averaged −1.2% for men (
P
>0.05) and −3.0% for women (
P
<0.01). In the fourth period, the slowdown of the decline in stroke mortality was most evident in the older age groups of men.

Conclusions

—

The findings suggested that along with an increasing aging population, the slowdown in the decline of stroke mortality rates, especially for men, is of considerable concern. Efforts to control stroke should be vigorously continued in the 2000s.