bluuebunny/crossref_metadata_2025 huggingface dataset:
Relaxation of Subarachnoid HemorrhageInduced Spasm of Rabbit Basilar Artery by the K
+
Channel Activator Cromakalim
Authors: Zuccarello Mario , Bonasso Christian L. , Lewis Adam I. , Sperelakis Nicholas , Rapoport Robert M.
Published: June 2011

Background and Purpose
Cerebral vasospasm resulting from subarachnoid hemorrhage (SAH) is refractory to most vasodilators. However, despite evidence that a mechanism underlying the vasospasm may be smooth muscle cell membrane depolarization resulting from decreased K
+
conductance, the ability of K
+
channel activators to relax the spasm has not been thoroughly investigated. The purpose of this study, therefore, was to investigate whether K
+
channel activation selectively relaxes SAH-induced vasospasm.

Methods
Three days after SAH in the rabbit, relaxation of the basilar artery in response to the K
+
channel activator cromakalim as well as to staurosporine (protein kinase C antagonist), forskolin (adenylate cyclase activator), and sodium nitroprusside (guanylate cyclase activator) was measured in situ with the use of a cranial window. Relaxation in response to these agents was also investigated in control vessels contracted with serotonin. Membrane potential of the smooth muscle cells of the basilar artery from SAH and control rabbit was measured in vitro with the use of intracellular microelectrodes.

Results
Cromakalim completely relaxed the SAH-induced spastic basilar artery, while staurosporine, forskolin, and sodium nitroprusside were significantly less efficacious. In contrast, sodium nitroprusside and forskolin were more efficacious relaxants in serotonin-contracted control vessels than in SAH vessels. The K
+
channel blocker glyburide and high [K
+
] prevented cromakalim-induced relaxation. Glyburide did not inhibit forskolin-induced relaxation of serotonin-contracted control vessels. Cromakalim concentration-dependently repolarized spastic basilar artery smooth muscle cells, and the repolarization was prevented by glyburide.

Conclusions
These results suggest that K
+
channel activation selectively relaxes SAH-induced vasospasm. We speculate that the ability of K
+
channel activators to selectively relax the spasm may be due, at least in part, to the underlying inhibition of K
+
channels after SAH.
Functional Outcome in Rats Transferred to an Enriched Environment 15 Days After Focal Brain Ischemia
Authors: Johansson Barbro B.
Published: June 2011

Background and Purpose
The aim was to determine whether a delayed transfer to an enriched environment improves outcome after focal brain ischemia.

Methods
Performance on a rotating pole, prehensile traction, limb placement, and postural reflexes were tested in 15 spontaneously hypertensive rats housed in standard laboratory cages for 2 weeks after middle cerebral artery ligation. Seven of the 15 rats were then transferred to an enriched environment, and the two groups were tested 1, 3, and 5 weeks later.

Results
The enriched environment significantly improved pole performance, prehensile traction, and limb placement.

Conclusions
Delayed postoperative environmental enrichment improves outcome in experimental stroke.
Asymptomatic Occlusive Lesions of Carotid and Intracranial Arteries in Japanese Patients With Ischemic Heart Disease
Authors: Uehara Toshiyuki , Tabuchi Masayasu , Hayashi Takatoshi , Kurogane Hiroyuki , Yamadori Atsushi
Published: June 2011

Background and Purpose
The purpose of this study was to elucidate the prevalence and degree of asymptomatic occlusive lesions in the carotid and intracranial arteries in Japanese patients with ischemic heart disease (IHD).

Methods
We performed carotid and intracranial MR angiography (MRA) on 67 patients (49 men, 18 women; age range, 40 to 78 years; mean age, 60.1 years) who had received selective coronary angiography for the clinical diagnosis of IHD. On the basis of these images, degree of stenosis in the regions of the bilateral carotid artery bifurcation and five regions of the intracranial arteries, ie, bilateral intracranial portions of the internal carotid arteries and the middle cerebral arteries and the basilar artery were estimated.

Results
Stenosis of more than 25% narrowing of the diameter of the target arteries was found in 15 patients (22.4%) in the extracranial carotid arteries and in 11 patients (16.4%) in the intracranial arteries. Most of the stenotic lesions were mild. The incidence of extracranial carotid stenosis and the severity of coronary atherosclerosis showed a significant correlation. The mean age of the patients with intracranial arterial lesions was statistically higher than those without intracranial lesions.

Conclusions
Our data suggest that asymptomatic occlusive lesions in the carotid and intracranial arteries are fairly common in Japanese patients with IHD, although the degree of stenosis is relatively mild. Coexistence of carotid atherosclerosis should be suspected in IHD patients with severe coronary atherosclerosis, and the possibility of atherosclerosis in the intracranial arteries should be considered in aged IHD patients.
Neuropsychological, Psychiatric, and Cerebral Blood Flow Findings in Vascular Dementia and Alzheimer’s Disease
Authors: Starkstein Sergio E. , Sabe Liliana , Vázquez Silvia , Tesón Alejandra , Petracca Gustavo , Chemerinski Erán , Di Lorenzo Guillermo , Leiguarda Ramón
Published: June 2011

Background and Purpose
Psychiatric, neuropsychological, and cerebral blood flow differences between patients with ischemic vascular dementia (IVD) or Alzheimer’s disease (AD) were examined.

Methods
A consecutive series of patients who met either the criteria of the National Institute of Neurological Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association for probable AD or the State of California AD Diagnostic and Treatment Centers criteria for probable IVD were included in the study. Twenty consecutive patients with IVD were matched for age, sex, and Mini-Mental State Examination scores with 40 consecutive patients with probable AD. Patients underwent a psychiatric interview, a neuropsychological assessment, and single-photon emission CT imaging with
99m
Tc-hexamethylpropyleneamine oxime.

Results
Patients with IVD showed significantly more severe anosognosia (
P
<.05) and emotional lability (
P
<.01) than AD patients, but no significant between-group differences were found in the frequency and severity of depression. IVD patients showed significantly more severe deficits in tests of planning, sequencing (
P
<.05), and verbal fluency (
P
<.05) as well as significantly more severe cerebral blood flow deficits in the basal ganglia (
P
<.01) and the frontal lobes (
P
<.001) than AD patients.

Conclusions
Patients with IVD showed a relatively more severe dysfunction of the frontal lobes as demonstrated by single-photon emission CT and expressed in specific psychiatric and neuropsychological changes than AD patients matched for age, sex, and severity of dementia.
Effects of Isovolemic Hemodilution on Hemodynamics, Cerebral Perfusion, and Cerebral Vascular Reactivity
Authors: Tu Yong-Kwang , Liu Hon-Man
Published: June 2011

Background and Purpose
To verify the hemorheological effects of isovolemic hemodilution on hemodynamics and cerebral perfusion of normal humans, we tested the efficacy of isovolemic hemodilution in systemic hemodynamics and cerebral blood flow augmentation and its influences in vascular reserve.

Methods
Isovolemic hemodilution was studied in a total of 13 normal healthy subjects. Regional cerebral blood flow was measured by the xenon-enhanced CT method. Cerebral vascular activity was measured by acetazolamide challenge. These measurements, in association with hemorheological and hemodynamic monitoring, were analyzed before and after isovolemic hemodilution with low-molecular-weight dextran.

Result
Our results showed significant change in hemodynamic parameters after isovolemic hemodilution, including tachycardia, a 24% increase of cardiac index, and decrease of peripheral vascular resistance. Both left and right heart work index increased as a consequence of increased cardiac index. Regional cerebral blood flow increased 35.0±2.5% at 3 hours after hemodilution and 20.2±3.9% at 1 week after hemodilution. Cerebral vascular reactivity decreased from 32.1±4.1% to 25.3±4.0% after hemodilution, implicating a certain degree of vasodilatation in the process of hemodilution. The whole procedure of hemodilution was completed in 52±6 minutes, and the subjects did not report discomfort during the procedure.

Conclusions
Isovolemic hemodilution in subjects with normal cerebral perfusion can augment cerebral blood flow efficiently in a rapid fashion, and this effect can last for at least a week. The mechanism of flow augmentation may be partially attributed to vasodilatation, which could be manifested as tachycardia, increased cardiac output, and decreased cerebral vascular reactivity.
Ankle Muscle Activity Before and After Botulinum Toxin Therapy for Lower Limb Extensor Spasticity in Chronic Hemiparetic Patients
Authors: Hesse S. , Krajnik J. , Luecke D. , Jahnke M.T. , Gregoric M. , Mauritz K.H.
Published: June 2011

Background and Purpose
Recent studies have been made of the novel treatment of lower limb spasticity after stroke with botulinum toxin A, and the results were based mostly on the clinical assessment made before and after treatment. This study investigated the effects of the toxin on ankle muscle activity during gait in patients with severe extensor spasticity. The questions posed were whether the toxin particularly diminishes the so-called premature muscle activity as a major cause of equinovarus deformity and whether different types of altered motor control allow a prediction of the outcome of the treatment.

Methods
In 12 chronic hemiparetic outpatients with pronounced lower limb spasticity, we injected 400 U botulinum toxin A into the soleus and tibialis posterior muscles and both heads of the gastrocnemius muscles. Ankle spasticity and complex gait analysis including kinematic electromyography (EMG) of the soleus and tibialis muscles were assessed before treatment and 4 weeks after the injection.

Results
Nine patients profited with a reduction of spasticity, improved gait ability, and a more normal temporal pattern of muscle activity with a prominent reduction of the premature activity of the plantar flexors. Eight patients exhibited a qualitative pattern (type I) corresponding to an increased stretch-reflex excitability. Three patients did not profit: their muscle tone, gait ability, and muscle activation remained stable or even deteriorated.

Conclusions
This study further supports the beneficial effects of botulinum toxin in the treatment of lower limb extensor spasticity. A correlation was observed between the clinical reduction of muscle tone, functional gait parameters, and a more normal EMG pattern with a predominant reduction of the premature activity of the plantar flexors. The qualitative type of EMG pattern corresponding to an increased stretch-reflex excitability (type I) was a positive predictor for the outcome.
Primitive Malignant Fibrous Histiocytoma of the Neck With Carotid Occlusion and Multiple Cerebral Ischemic Lesions
Authors: Martin-Negrier Marie-Laure , Belleannée Genevieve , Vital Claude , Orgogozo Jean-Marc
Published: June 2011

Background
Emergence of a malignant tumor at the site of an operation is a rare event and most often arises in association with retained foreign material.

Case Description
We describe a patient who 1 year after a left carotid endarterectomy for typical atheromatous lesions presented with several transient ischemic attacks with stepwise worsening of the deficit and rapid death. A few weeks before, a tumor of the neck had appeared at the site of the previous endarterectomy. At postmortem examination, we found a malignant histiocytofibroma occluding the left carotid artery, with several recent ischemic foci in the corresponding cerebral hemisphere without metastasis or tumor emboli.

Conclusions
This observation is unusual owing to the histological type of the neoplasm and to the circumstance of emergence of the neoplasm.
Comparing Stroke Incidence Worldwide
Authors: Sudlow C.L.M. , Warlow C.P.
Published: June 2011

Background
Comparing stroke rates in different parts of the world and at different points in time may increase our understanding of the disease. Comparisons are only meaningful if they are based on studies that use similar definitions, methods, and data presentation.

Summary of Review
We discuss the criteria that make such studies comparable, drawing on the experiences of recent studies performed around the world. If only those studies that fulfill the proposed criteria for comparison are considered, comparable data do not exist for vast areas of the world, including Africa, Asia, and South America. The importance of complete, community-based case ascertainment, including strokes managed outside the hospital, is emphasized. An approach for measuring and comparing the incidence of the pathological types of stroke (cerebral infarction, primary intracerebral hemorrhage, and subarachnoid hemorrhage) and subtypes of cerebral infarction is suggested.

Conclusions
The “ideal” stroke incidence study does not exist, but studies closely approaching it will reveal the most reliable and comparable results. There is a need for further studies to fill the gaps in our knowledge of the worldwide incidence of stroke, particularly for developing countries.
Cerebral Blood Flow Alteration by Acetazolamide During Carotid Balloon Occlusion
Authors: Okudaira Yojiro , Arai Hajime , Sato Kiyoshi
Published: June 2011

Background and Purpose
We attempted to clarify the role of the acetazolamide-reactive mechanism in cerebral hemodynamic autoregulation and to establish a useful method of estimation using the acetazolamide test.

Methods
We examined 18 patients whose cerebral hemodynamics were considered to be normal and whose cerebral blood flow (CBF) was maintained during the balloon occlusion test (BOT) of the internal carotid artery. We measured the mean stump pressure (MSTP) and the mean CBF in the middle cerebral arterial territory using a xenon-enhanced CT system during BOT with and without acetazolamide activation. We obtained the asymmetry ratio (AR=occluded CBF/contralateral CBF) and the increased CBF parameters caused by acetazolamide activation expressed as an absolute value (ΔCBF) and a percentage (%ΔCBF) for the occluded side.

Results
AR during BOT with and without acetazolamide activation differed significantly (
P
<.001, paired
t
test) despite the lack of significant MSTP changes. Furthermore, although there was no significant correlation between MSTP and AR without acetazolamide activation, a positive significant correlation was detected with acetazolamide activation (
r
=.634,
P
=.005, linear regression analysis). There were significant correlations between ΔCBF and MSTP (
r
=.574,
P
=.013) and %ΔCBF and MSTP (
r
=.640,
P
=.004).

Conclusions
We consider that the acetazolamide-reactive mechanism functions as autoregulation at the lower end of the autoregulatory range. The acetazolamide test, using %ΔCBF or ΔCBF as parameters (which both directly reflect MSTP), is useful for estimating the cerebral perfusion pressure decrease and presence of hemodynamic compromise.
Effect of Time and Cerebrovascular Symptoms on the Prevalence of Microembolic Signals in Patients With Cervical Carotid Stenosis
Authors: Forteza A.M. , Babikian V.L. , Hyde C. , Winter M. , Pochay V.
Published: June 2011

Background and Purpose
High-intensity transient signals (HITS) detected by transcranial Doppler ultrasonography correspond to microemboli in intracranial arteries. The aim of this study was to determine the time course of cerebral microembolism in patients with symptomatic internal carotid artery stenosis and to assess its relation to specific symptoms of cerebral ischemia.

Methods
On the basis of criteria established a priori, 69 middle cerebral arteries were selected from a series of consecutive studies obtained at our neurovascular laboratory. All patients had radiological evidence of cervical internal carotid artery disease and had corresponding symptoms. A TC-2000 instrument equipped with special software for microembolus detection was used. Accepted signals were unidirectional from baseline, had a chirping sound, were 9 dB higher than the surrounding blood, and lasted 25 milliseconds or more.

Results
HITS were identified in 20 of 69 (29%) arteries. The median interval between onset of symptoms and time of testing was 4 days for HITS-positive arteries and 12 days for those that were HITS negative (
P
=.0046). Fourteen of 32 (44%) arteries with transient ischemic attacks and 6 of 37 (16%) arteries with cerebral infarction were HITS positive (
P
=.012).

Conclusions
In patients with symptomatic carotid stenosis, HITS are detected more frequently when patients are tested soon after symptoms of cerebral ischemia. HITS are also more prevalent in the territories of arteries with transient ischemic attacks rather than cerebral infarction. These findings may have diagnostic and therapeutic implications.
Ischemic Stroke and Incomplete Infarction
Authors: Garcia Julio H. , Lassen Niels A. , Weiller Cornelius , Sperling Bjørn , Nakagawara Jyoji
Published: June 2011

Background
The concept of selective vulnerability or selective loss of individual neurons, with survival of glial and vascular elements as one of the consequences of a systemic ischemic-hypoxic insult (eg, transient cardiac arrest or severe hypotension), has been recognized for decades. In contrast, selective neuronal death as one of the lesions that may develop in the brain after occluding an intracranial artery is an idea not readily acknowledged in the current medical literature dealing with human stroke.

Summary of Review
A review of pertinent publications reveals that selective neuronal injury after middle cerebral artery occlusion was observed in autopsy specimens over 40 years ago, although its pathogenesis remains unclear. Recent observations in both humans and animals suggest that selective neuronal necrosis (rather than infarct) is the consequence of either a short-term arterial occlusion or permanent occlusion accompanied by ischemia of moderate severity. During the acute and subacute stages of an ischemic stroke, the loss of a limited number of neurons (ie, incomplete infarction) does not result in structural changes discernible by either CT or conventional MRI. However, the loss of a selected number of neurons may be demonstrable in vivo by calculating the corresponding loss of benzodiazepine receptors. The use of specific radiotracers in combination with single-photon emission CT or positron emission tomography allows demonstration of a decrease in γ-aminobutyric acid–ergic receptor sites at places where many neurons have been lethally injured.

Conclusions
We aim to alert physicians to the potential development of incomplete brain infarctions in patients with intracranial arterial occlusions. Recognizing incomplete infarcts is particularly important in the context of stroke therapy with thrombolytic and neuroprotective agents. This brain lesion is likely to be the consequence of an arterial occlusion with a resultant ischemia of moderate severity (eg, regional blood flows in the range of 15 to 20 mL·100 g
−1
·min
−1
).
Will Increased Awareness Among Physicians of the Significance of Sudden Agonizing Headache Affect the Outcome of Subarachnoid Hemorrhage?
Authors: Tolias Christos M. , Choksey Munchi S.
Published: June 2011

Background and Purpose
The most common symptom associated with aneurysmal minor bleed (“warning leak”) is a sudden agonizing headache. Early screening of these patients may improve the outcome of subarachnoid hemorrhage and may be highly cost-effective.

Methods
We conducted an extensive retrospective audit of subarachnoid hemorrhage over the last 10 years in the region of Coventry and Warwickshire, England, and initiated a continuous campaign among all physicians in the region for early neurosurgical referral of patients with sudden agonizing headache.

Results
Over the last 10 years the incidence of subarachnoid hemorrhage in the region was 8.7/100 000 per year. Surgical activity was 34% and early mortality 45.2%. Functional outcome, both overall and by grade on admission, was within internationally accepted levels. Warning leak symptoms before admission were experienced by 20% of patients. These patients sought medical advice but were not referred immediately to the neurosurgical unit.

Conclusions
We have established our population as valid historical controls and outlined our campaign strategy. Lowering the clinical threshold at which patients with sudden agonizing headache are screened for aneurysms or arteriovenous malformations will undoubtedly increase diagnostic costs. However, for reasons given in the text, we estimated the cost per quality-adjusted life year gained to be £1000 ($1500).
Stroke in the Young in Israel
Authors: Rozenthul-Sorokin Naomi , Ronen Revital , Tamir Ada , Geva Hana , Eldar Reuben
Published: June 2011

Background and Purpose
Data on stroke in the young in Israel are fragmentary. To obtain an overall perspective and to assess the nature and magnitude of the problem, a study was conducted on stroke occurrence in the young population during 1 year. Incidence and outcomes are reported in this communication.

Methods
We conducted a prospective ascertainment of first stroke in all permanent residents of Israel aged 17 to 49 years who were referred to all acute-care hospitals in the country or died before reaching them.

Results
We identified 253 first stroke victims in the studied population; 62.8% were male. The age- and sex-adjusted incidence rate for all types of stroke was 10.36/100 000 per year (males, 13.00; females, 7.71). The majority of strokes (80.6%) were cerebral infarctions, with 9.9% intracerebral hemorrhages, 7.9% subarachnoid hemorrhages, and 1.6% strokes of unspecified type. The case-fatality rate for all types of stroke was 9.9% (mortality within the first 4 weeks after the event, on average 6 days). The survival rate was 95% for cerebral infarctions, 64% for intracerebral hemorrhages, and 80% for subarachnoid hemorrhages; 86.7% of all survivors remained with an impairment resulting in a disability.

Conclusions
Incidence rates were similar to those reported from developed Western countries. The case-fatality rate of 9.9% and the considerable percentage of survivors with a disability in a population at the beginning of their family, professional, and social lives indicate the magnitude of the problem.
Increased Expression of TGF-β1 in Brain Tissue After Ischemic Stroke in Humans
Authors: Krupinski Jerzy , Kumar Pat , Kumar Shant , Kaluza Jozef
Published: June 2011

Background and Purpose
Occlusion in cerebral vessels results in ischemic stroke and is followed by proliferation of microvessels, ie, angiogenesis. The process is particularly marked in the border zone of the infarct, known as the ischemic penumbra. This increase in vascularization is likely to be caused by the action of angiogenic factors, such as TGF-β1, which is a powerful regulator of angiogenesis.

Methods
In this study we examined 10 brain samples from patients who suffered from ischemic stroke for the expression of mRNA encoding TGF-β1.

Results
The ischemic penumbra contained the highest levels of TGF-β1 mRNA, whereas the normal contralateral hemispheres had the least (
P
<.001, Mann-Whitney
U
test). Unlike those from normal brain, protein extracts from infarcted tissue contained active TGF-β1 as a 25-kD band in Western blot analysis. Extracts from the penumbra also contained a 12.5-kD isoform of TGF-β1. Both penumbra and infarct contained TGF-β1 immunoreactive products as assessed with immunohistochemistry, whereas very weak staining was observed in the contralateral hemisphere.

Conclusions
These results suggest that TGF-β1 is important in the pathogenesis of the angiogenic response in ischemic brain tissue and its modulation may be used for therapeutic purposes.
Thrombolytic Therapy of Acute Basilar Artery Occlusion
Authors: Brandt Tobias , von Kummer Rüdiger , Müller-Küppers Markus , Hacke Werner
Published: June 2011

Background and Purpose
Thrombolysis may reduce mortality after acute basilar artery (BA) occlusion. We intended to find variables affecting recanalization and clinical outcome in patients with BA occlusion undergoing thrombolytic therapy.

Methods
We analyzed in retrospect the clinical and angiographic data of a consecutive series of 51 patients treated with intra-arterial urokinase (n=44; 0.3 to 1.5 mIU) or intravenous or intra-arterial recombinant tissue plasminogen activator (n=7; 22 to 100 mg). We identified effective variables by multiple logistic regression analyses and univariate tests.

Results
Sites of occlusion were the caudal (n=23), middle (n=18), and distal (n=10) segments of the BA. The pathogenesis was embolism in 35 and local atherothrombosis in 16 patients. Collateral circulation was good in 32 patients and poor or absent in 19 patients. Recanalization was achieved in 26 of 51 (51%) patients and was associated with occlusions of embolic etiology (
P
=.0025). Mortality was 46% (12/26) in the recanalization group and 92% (23/25) in the nonrecanalization group (
P
=.0004). Other independent variables affecting mortality were length of BA obstruction (
P
=.0011), age (
P
=.0008), and collateral state (
P
=.0454). After follow-up (median, 32 months), 10 of the 16 survivors were only minimally impaired, with a Barthel Index score of 95 or greater; 5 patients were moderately and 1 severely disabled.

Conclusions
Recanalization of acute BA occlusion reduces mortality significantly. Length of BA obstruction and state of the collaterals are additional independent variables affecting survival. Young patients with monosegmental embolic occlusion of the BA seem to have the best chance to considerably profit from thrombolysis.
Treatment of Focal Cerebral Ischemia With Synthetic Oligopeptide Corresponding to Lectin Domain of Selectin
Authors: Morikawa Eiharu , Zhang Shi-Ming , Seko Yoshinori , Toyoda Tomikatsu , Kirino Takaaki
Published: June 2011

Background and Purpose
Synthetic oligopeptides with amino acid sequences of the lectin domain of selectin block selectin-mediated cell adhesion in vitro, which may be applied to a therapeutic intervention to attenuate acute inflammatory reactions. To evaluate the efficacy of such treatment against ischemic brain injury, the effects of administering a selectin oligopeptide that selectively blocks selectin-mediated cell adhesion on histological outcome and on cerebral blood flow (CBF) were studied in models of rodent focal cerebral ischemia.

Methods
Spontaneously hypertensive rats were anesthetized with halothane. Permanent focal cerebral ischemia was induced by tandem left middle cerebral artery (MCA) and common carotid artery (CCA) occlusion. Focal cerebral ischemia with partial reperfusion was introduced by reperfusing the CCA after 2 hours of tandem MCA/CCA occlusion. A synthetic oligopeptide (amino acid residues 23-30 from N terminal) of E-selectin was dissolved in physiological saline and was injected intravenously at a dosage of 2 mg/kg or 10 mg/kg before artery occlusion. Control animals received equivalent volumes of physiological saline or 10 mg/kg of synthetic oligopeptide with a scrambled amino acid sequence. Twenty-four hours after the occlusion, seven coronal brain slices were stained with 2,3,5-triphenyltetrazolium chloride, and the volume of ischemic injury was calculated. In a separate set of animals, regional CBF was monitored with laser-Doppler flowmetry at the dorsolateral cerebral cortex during 2-hour ischemia and 30 minutes after partial reperfusion.

Results
The volume of ischemic injury did not differ among groups in permanent ischemia. In ischemia with partial reperfusion, 10 mg/kg selectin oligopeptide, but not the same dosage of scrambled oligopeptide, significantly reduced the volume of ischemic injury (95±13, 73±11, 55±6, and 111±14 mm
3
for saline [n=11]; 2 mg/kg [n=10] and 10 mg/kg [n=16] selectin oligopeptide and 10 mg/kg scrambled oligopeptide [n=6], respectively;
P
<.01 by one-way ANOVA followed by the Tukey test). Laser-Doppler flowmetry demonstrated a larger increase in CBF after reperfusion of the CCA in the 10-mg/kg selectin oligopeptide group.

Conclusions
Our data demonstrate that administration of a synthetic oligopeptide corresponding to the lectin domain of selectin decreases the size of ischemic injury after transient, but not after permanent, focal cerebral ischemia as evaluated at 24 hours after onset of ischemia. These effects were associated with an improved CBF at the dorsolateral cerebral cortex after partial reperfusion.
Plasma Lipoprotein(a) Is an Independent Factor Associated With Carotid Wall Thickening in Severely but Not Moderately Hypercholesterolemic Patients
Authors: Baldassarre Damiano , Tremoli Elena , Franceschini Guido , Michelagnoli Silvia , Sirtori C.R.
Published: June 2011

Background and Purpose
To evaluate whether high levels of low-density lipoprotein cholesterol (LDL-C) may promote the atherogenic effect of lipoprotein(a) [Lp(a)], we investigated the association between elevated Lp(a) levels and thickening of intima plus media in the common carotid artery (CC-IMT) in patients with different degrees of hypercholesterolemia.

Methods
One hundred type II hypercholesterolemic patients and 25 normolipidemic subjects were selected for the study. Plasma lipid and lipoprotein levels were determined enzymatically; Lp(a) levels were determined by enzyme-linked immunosorbent assay. An Lp(a) concentration >30 mg/dL was arbitrarily considered a risk factor. For each patient mean CC-IMT was determined by B-mode ultrasound; in 60 patients and in the 25 control subjects, the maximal IMT in the entire carotid tree was also determined.

Results
CC-IMT values were higher in hypercholesterolemic patients with plasma Lp(a) levels >30 mg/dL than in those with lower levels (
P
<.01). CC-IMT and maximal IMT directly and independently correlated with plasma levels of Lp(a) (
r
=.33 and
r
=.25, respectively; both
P
<.05). The effect of LDL-C concentrations on the relationship between IMT and Lp(a) was investigated by dividing the patients into quartiles of plasma LDL-C levels. After stratification, CC-IMT significantly correlated with plasma Lp(a) levels in the patients with severe hypercholesterolemia (LDL-C >5.2 mmol/L) but not in patients in the lowest quartile, ie, those with moderate hypercholesterolemia. No correlation between CC-IMT and Lp(a) was found in normolipidemic control subjects.

Conclusions
Elevated plasma levels of Lp(a) can be considered an additional independent factor associated with thickening of the common carotid arteries in patients with severe hypercholesterolemia but not in those with moderate hypercholesterolemia or in normocholesterolemic subjects.
Comparison of Additive and Multiplicative Models of Regional Variation in the Decline of Stroke Mortality in the United States
Authors: Lanska Douglas J. , Peterson Patrick M.
Published: June 2011

Background and Purpose
Although previous studies have shown that geographic variation in the decline of stroke mortality rates may be an important contributor to the changing geographic distribution of stroke mortality in the United States, some concern has been raised that this phenomenon may be model dependent. This study examines the geographic variation in the decline of stroke mortality rates in the United States with the use of both additive and multiplicative models.

Methods
National Center for Health Statistics and Bureau of the Census data were used to assess regional-level temporal trends of underlying-cause stroke mortality rates in the United States for 1979 through 1989. Both additive and multiplicative models were fit to the data.

Results
Underlying-cause stroke mortality rates have declined fairly steadily in all regions of the United States and for all race-sex groups, although there was significant regional variation in the rate of decline during the period 1979 through 1989. The South, which initially had the highest rates, had the most rapid decline for all race-sex groups when either additive or multiplicative models were used.

Conclusions
From 1979 through 1989 there was significant geographic variation in the rate of decline of stroke mortality rates, with the most rapid rates of decline in the South. As a result, there has been a decrease in interregional variation in stroke mortality rates.
Neuroexcitatory Amino Acids and Their Relation to Infarct Size and Neurological Deficit in Ischemic Stroke
Authors: Castillo José , Dávalos Antoni , Naveiro Javier , Noya Manuel
Published: June 2011

Background and Purpose
The participation of excitatory amino acids (EAAs) in the pathogenesis of ischemic neuronal lesion has been experimentally demonstrated, but clinical experience is scarce. Our objective was to examine EAA levels during the acute phase of cerebral infarction in relation to infarct size and intensity of neurological deficit.

Methods
Using high-performance liquid chromatography, we determined the glutamate, aspartate, taurine, and glycine concentrations in the plasma and cerebrospinal fluid (CSF) of 128 patients with ischemic cerebral infarction confirmed by CT and 43 control subjects. Blood and CSF samples were obtained on admission within the first 24 hours from symptom onset. The severity of the neurological deficit was assessed with the Canadian Stroke Scale immediately after these tests and at 48 hours after inclusion in the study. Infarct volume was determined in a second CT performed between the 4th and 7th day after the patient’s inclusion.

Results
The concentration of plasmatic glutamate was 121.39±80.89 μmol/L in the control group and 163.71±103.13 μmol/L in the patient group (
P
=.015); in CSF it was 3.46±1.20 μmol/L in control subjects and 6.55±4.65 μmol/L in patients (
P
<.0001). The concentration of glycine in plasma was 158.02±32.15 μmol/L in control subjects and 189.37±74.04 μmol/L in patients (
P
=.007); in CSF it was 6.18±2.28 μmol/L in control subjects and 11.23±6.96 μmol/L in patients (
P
<.0001). The concentrations of glutamate in plasma and in CSF were significantly higher in patients with large cerebral infarcts and in those with cortical infarcts. Levels of glutamate and glycine in plasma and CSF were significantly higher in patients with a higher degree of neurological deficit.

Conclusions
Our results support the excitotoxic activity of glutamate and glycine in patients with cerebral infarction.
Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Stroke Patients
Authors: Lindgren Arne , Lindoff Claes , Norrving Bo , Åstedt Birger , Johansson Barbro B.
Published: June 2011

Background and Purpose
Abnormal endogenous fibrinolytic activity may be a risk factor for stroke. Since the possible variation of tissue-type plasminogen activator (TPA) antigen and plasminogen activator inhibitor-1 (PAI-1) antigen concentrations over time after stroke has been rarely studied, it was examined in plasma from stroke patients in the acute and convalescent phases of the disease and in a control group.

Methods
Plasma concentrations of TPA and PAI-1 were determined in 135 stroke patients and in 77 control subjects. All but 4 patients were examined within 7 days after stroke onset, and 32 patients and 18 control subjects were reexamined 2 to 4 years later.

Results
In the acute phase, stroke patients had significantly higher TPA (median, 10 μg/L) and PAI-1 (median, 14 μg/L) antigen concentrations, compared with control subjects (median values, 6 μg/L [
P
=.0001] and 8 μg/L [
P
<.01], respectively); TPA levels were higher in both the cerebral infarction (n=122) and cerebral hemorrhage (n=12) subgroups, whereas PAI-1 levels were higher in the cerebral infarction subgroup only. Stepwise logistic regression analysis (with correction for age, sex, history of hypertension, diabetes mellitus, and heart disease) showed TPA antigen level to be an independent discriminator between the cerebral infarction subgroup and control subjects (
P
=.0001), whereas the corresponding difference for PAI-1 antigen levels just failed to reach significance (
P
=.05). TPA antigen levels were correlated with concentrations of serum cholesterol (Spearman’s ρ=0.15;
P
<.05), serum triglyceride (ρ=0.33;
P
=.0001), and plasma homocysteine (ρ=0.19;
P
<.01). PAI-1 antigen levels were correlated with serum triglyceride levels only (ρ=0.41;
P
=.0001). At reexamination after 2 to 4 years, neither TPA nor PAI-1 levels had changed significantly from the baseline values.

Conclusions
In stroke patients, high TPA antigen concentrations may indicate an activation of the fibrinolytic system or may be due to a delayed clearance of TPA complexed with inhibitors. High PAI-1 antigen concentrations in patients with cerebral infarction represent increased fibrinolytic inhibition. The findings in this longitudinal study suggest that TPA and PAI-1 antigen concentrations both differ little between the acute and convalescent phases after stroke.
Assessment of Regional Cerebral Blood Volume in Acute Human Stroke by Use of Single-Slice Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
Authors: Röther Joachim , Gückel Friedemann , Neff Wolfgang , Schwartz Andreas , Hennerici Michael
Published: June 2011

Background and Purpose
The purpose of this study was to evaluate the clinical usefulness of dynamic susceptibility contrast-enhanced MRI (DSC-MRI) in acute cerebral ischemia.

Methods
During bolus injection of gadolinium-diethylenetriamine pentaacetic acid, a series of rapid T
2
*-weighted images was recorded from one slice. Concentration-time curves and images of regional cerebral blood volume (rCBV) were calculated from this data set. DSC-MRI, MR angiography, conventional spin-echo MRI (SE-MRI), and CT were performed in 11 patients within 6 hours after stroke onset and before thrombolytic or anticoagulant treatment was begun. A follow-up MRI examination was performed 24 to 48 hours after stroke onset.

Results
In 7 of 11 patients (group 1) with territorial infarcts of the middle (n=6) or posterior cerebral artery (n=1), DSC-MRI showed reduced rCBV in the affected territory before conventional SE-MRI displayed ischemic lesions. DSC-MRI was helpful to differentiate severely ischemic tissue from peri-infarct parenchyma. Partial reperfusion (n=3), unchanged reduction of rCBV (n=2), and progressive reduction of rCBV (n=2) were observed in the follow-up study. Normal DSC-MRI findings were present in 4 of 11 patients (group 2) with lacunar infarcts.

Conclusions
DSC-MRI accomplished the detection of the ischemic territory in the very early stage (<6 hours) before SE-MRI delivered unequivocal results. DSC-MRI might be helpful to discriminate completely ischemic tissue from potentially salvageable ischemic parenchyma at risk and may play an important role in stroke therapy and evaluation.
In Vivo Evaluation of Antiplatelet Agents in Gerbil Model of Carotid Artery Thrombosis
Authors: Nishimura Hiroyuki , Naritomi Hiroaki , Iwamoto Yasumichi , Tachibana Hisao , Sugita Minoru
Published: June 2011

Background and Purpose
Antiplatelet agents are widely used for the prevention of ischemic stroke. However, their effects on thrombus formation have rarely been evaluated in experimental animals in vivo. We introduce methods for evaluating antithrombotic action in gerbils and the effects of several antiplatelet agents on thrombus formation.

Methods
In gerbils 8 to 10 weeks of age, we tightly compressed the unilateral common carotid artery for 2 minutes using the device prepared for this purpose to damage the endothelium. Thrombus formation in the damaged artery was observed directly through the microscope for 30 minutes. In six animals, the damaged artery was examined immediately after the experiments by electron microscopy. We studied the effects of antiplatelets by injecting the drugs intravenously 10 minutes before endothelial damage.

Results
In control studies, 70% to 90% of animals developed thrombi after arterial compression. The electron microscopic examination displayed endothelial damage in association with platelet thrombus at the damaged site. Administration of 2 mg/kg aspirin, 3 and 10 mg/kg ticlopidine, and 0.3 and 1.0 mg/kg ibudilast, a novel prostacyclin accelerator, decreased the frequency of thrombus formation significantly, whereas 20 mg/kg aspirin and 20 mg/kg dipyridamole failed to decrease thrombus formation.

Conclusions
This model is considered useful for evaluating the antithrombotic effects of drugs because of its feasibility and high reproducibility. The present results support the view that a lower dose of aspirin may prevent cerebral vascular accidents as efficiently as a higher dose of aspirin.
Confocal Microscopic Characterization of a Lesion in a Cerebral Vessel of the Stroke-Prone Spontaneously Hypertensive Rat
Authors: Arribas Silvia M. , Gordon John F. , Daly Craig J. , Dominiczak Anna F. , McGrath John C.
Published: June 2011

Background and Purpose
Hypertension is a major risk factor for stroke and is associated with alterations in vascular structure and function. The aim of this study was to determine vascular function, wall morphology, and vascular smooth muscle cell (VSMC) arrangement in basilar arteries from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive control strain Wistar-Kyoto rats (WKY). The effect of perindopril treatment on SHRSP structure and function was also assessed.

Methods
VSMC orientation was determined with laser-scanning confocal microscopy and computer-assisted image processing in basilar arteries stained with 5(6)-carboxyfluorescein (wavelengths: excitation, 488; emission, 515) or propidium iodide (excitation, 529; emission, 550). Measurements of wall morphology and functional responses to serotonin and KCl were assessed with wire myography.

Results
In the WKY basilar arteries, VSMCs were uniformly oriented perpendicular to the longitudinal axis of the vessel, whereas in the SHRSP there were localized foci of VSMC geometric disorganization, with a significant deviation from 90°. The SHRSP basilar arteries also showed structural remodeling and reduced contractile responses to serotonin and KCl. Perindopril treatment normalized blood pressure, prevented wall morphology alterations, and improved function but had no effect on VSMC disorganization.

Conclusions
This is the first demonstration of lesions of VSMC geometric disorganization in a cerebral artery from a stroke-prone genetically hypertensive rat strain. These structural abnormalities are independent of blood pressure. Their functional sequel may play a role in the pathogenesis of stroke in this model.
Activated Protein C Resistance in Ischemic Stroke Not Due to Factor V Arginine
506
→Glutamine Mutation
Authors: Fisher Mark , Fernández José A. , Ameriso Sebastian F. , Xie Dangci , Gruber Andras , Paganini-Hill Annlia , Griffin John H.
Published: June 2011

Background and Purpose
Resistance to activated protein C (APC), a natural plasma anticoagulant, is the most common identifiable risk factor for venous thromboembolic disease. One point mutation in coagulation factor V that renders it APC-resistant is found in >90% of APC-resistant venous thrombosis patients. To determine the prevalence of APC resistance and of this factor V mutation in stroke, we screened a group of ischemic stroke patients.

Methods
Hispanic ischemic stroke patients were screened using two different activated partial thromboplastin time-based assays. One assay using neat patient plasma determined APC resistance, and the other assay using patient plasma diluted into factor V-deficient plasma determined APC-resistant factor V, including the Arg
506
→Gln mutation. Results were compared with those in 31 Hispanic control subjects of similar ages.

Results
Six of 63 (9.5%) stroke patients had APC resistance compared with none of 31 (0%) control subjects. No patient or control subject had APC-resistant factor V, ie, the factor V Arg
506
→Gln mutation.

Conclusions
In Hispanic patients with ischemic stroke, the incidence (approximately 10%) of APC resistance is not caused by the factor V Arg
506
→Gln mutation. APC resistance not caused by this factor V mutation may be a risk factor for ischemic stroke in this population.
Five-Year Follow-up of Patients After Thromboendarterectomy of the Internal Carotid Artery
Authors: Hirschl Mirko , Kundi Michael , Blazek Gerhard
Published: June 2011

Background and Purpose
In patients after myocardial infarction, baroreceptor sensitivity has been identified as a factor of prognostic relevance. This study was designed to assess the effects of an increased baroreceptor sensitivity in patients after surgery in the area of the internal carotid artery with respect to blood pressure variability, therapeutic interventions, and vascular events during a 5-year follow-up.

Methods
Receptor sensitivity before and immediately after carotid surgery was measured in 84 patients. Blood pressure variability, carotid artery status, and echocardiographic findings were assessed before and after surgery and at the end of follow-up. Vascular events as well as changes in blood pressure therapy during the follow-up period were evaluated.

Results
Significant negative correlations between an increase of baroreceptor sensitivity after surgery and the range of systolic (
r
=−.47;
P
<.001) and diastolic (
r
=−.33;
P
<.01) blood pressure were found for the immediate postoperative period. For the range of systolic blood pressure, this relation persisted (4.3 to 7 years after surgery) at the end of the observation period (
r
=−.38;
P
<.001). An inverse relation to the increase in baroreceptor function was also found for the average annual number of therapeutic interventions during follow-up (
r
=−.38;
P
<.001). Furthermore, the subgroup of patients without a postoperative increase of receptor sensitivity was characterized by a significantly higher risk of major vascular events (log-rank test,
P
<.018).

Conclusions
Because an improvement of receptor sensitivity after carotid surgery is related to a long-lasting reduction of blood pressure levels and variability, baroreceptor function may be considered an indirect indicator for the later postoperative course.
Transcranial Doppler in the Evaluation of Internal Carotid Artery Dissection
Authors: Srinivasan Jayashree , Newell David W. , Sturzenegger Matthias , Mayberg Marc R. , Winn H.R.
Published: June 2011

Background and Purpose
A subject with dissection of the internal carotid artery (ICA) may present with a variety of symptoms, from headache to stroke. Thus far, it has not been possible to identify the subset of patients at risk for cerebral ischemia. Because the majority of these ischemic events are secondary to embolic phenomena, we used transcranial Doppler (TCD) evaluation with emboli monitoring to study 17 consecutive patients with ICA dissection treated at Harborview Medical Center, Seattle, Wash, during a 2-year period from 1992 until 1994.

Methods
Ten patients with ICA dissection secondary to trauma and seven with spontaneous ICA dissection were diagnosed by carotid angiography and studied by TCD from the time of diagnosis through initiation of therapy. Emboli monitoring was performed in the middle cerebral artery (MCA) ipsilateral to the dissection at the initial evaluation and intermittently thereafter to ensure that the emboli stopped with treatment.

Results
Emboli were detected in the MCA distal to the dissection in 10 of 17 patients (59%). Patients with microemboli detected by TCD presented with a stroke (70%) much more frequently than those without emboli (14%) (
P
=.0498). The presence of a pseudoaneurysm did not increase the risk of either microemboli or stroke.

Conclusions
We have demonstrated a high incidence of intracranial microemboli in the MCA distal to carotid dissections and a significant correlation between the presence of emboli and stroke. TCD can therefore be used as an adjunctive tool to manage patients with suspected carotid dissection and may prove useful in evaluating the efficacy of treatment in reducing microemboli and subsequent stroke.