bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of angiogenesis in patients with cerebral ischemic stroke.
Authors: Krupinski J , Kaluza J , Kumar P , Kumar S , Wang J M
Published: June 2011

Stroke is one of the most common causes of mortality and morbidity in the Western world. It results from the occlusion of a cerebral artery followed by severe disturbances in blood supply through microvessels to brain tissue. Despite an extensive literature its pathophysiology is poorly understood, and this has severely impeded the logical development of therapy.

Brains were obtained from 10 patients aged 46 to 85 years with survival times of 5 to 92 days after their stroke. Infarcted areas and representative control tissues from the contralateral uninvolved brain hemisphere were collected. Microvessel density was measured microscopically. A total of 6520 microvessels were scored in 10,801 areas. The level of activation of the endothelial cells was studied by immunohistochemistry using three monoclonal antibodies, viz, E-9, raised against activated endothelial cells; IG11, recognizing vascular cell adhesion molecule-1; and anti-proliferating cell nuclear antigen. Angiogenic activity in tissue extracts was examined using an in vivo chicken chorioallantoic membrane assay.

There was a statistically significant increase in the number of microvessels (Wilcoxon log-rank test; P < or = .01) in 9 of 10 infarcted brain tissues when compared with their contralateral normal hemisphere. In these patients the higher blood vessel counts correlated with longer survival, as ascertained by Spearman's p analysis (P < .02). The number of microvessels filled with blood cells was significantly lower in the infarcted hemispheres (P < .01). In contrast, statistically significant increased numbers of empty microvessels occurred in infarcted tissues compared with the contralateral hemisphere. Monoclonal antibody E-9 reacted weakly with normal-brain vascular endothelial cells; anti-proliferating cell nuclear antigen and IG11 were virtually negative. All three antibodies strongly stained the blood vessels of stroke tissues. The stroke tissues contained angiogenic activity, as shown by the induction of new blood vessels in a chorioallantoic membrane assay.

We have shown that stroke causes active angiogenesis that is more developed in the penumbra. Further experiments are needed to determine if this angiogenesis has beneficial effect.
Preischemic hyperglycemia leads to delayed postischemic hyperthermia.
Authors: Uchino H , Lundgren J , Smith M L , Siesjö B K
Published: June 2011

Temperature alterations are known to influence the outcome of transient ischemia, even when instituted in the postischemic period. Since preischemic hyperglycemia aggravates ischemic brain damage, the question of whether hyperglycemic animals become hyperthermic arose. To explore this possibility, we measured body temperature telemetrically in normoglycemic and hyperglycemic rats subjected to 10 minutes of forebrain ischemia at a body (and brain) temperature of 37 degrees C.

Isoflurane-anesthetized animals were subjected to 10 minutes of forebrain ischemia under normoglycemic or hyperglycemic conditions. Temperature changes after ischemia were measured by means of a telemetric temperature coil.

In normoglycemic animals, temperature decreased to 35.6 +/- 1.1 degrees C (mean +/- SD) during the first 4 hours of recovery, after which it gradually increased to normal values (38 degrees C). Hyperglycemic animals behaved differently in that they remained normothermic for approximately 10 hours during recovery and later became hyperthermic, with core temperatures rising above 39 degrees C. The rise in temperature was not due to the osmotic load of the glucose administered because infusion of mannitol, which gave a comparable increase in plasma osmolality, failed to cause delayed postischemic hyperthermia. Excessive hypercapnia during ischemia in normoglycemic animals, which produces cerebral acidosis of a magnitude similar to that of hyperglycemia and is known to aggravate ischemic lesions, likewise failed to induce hyperthermia. When post-ischemic seizures ensued in hyperglycemic subjects, temperature was 39.8 +/- 0.6 degrees C. Animals with seizures invariably died. To evaluate the influence of postischemic hyperthermia on the outcome, an additional series of experiments was performed in which delayed hyperthermia was avoided by gentle cooling (n = 6) or by acetaminophen administration (n = 5). Although these procedures prevented delayed hyperthermia, they neither blocked seizure induction nor affected the fatal outcome. Postischemic seizures developed when the core temperatures of animals were 37.9 +/- 0.1 degrees C and 37.8 +/- 0.2 degrees C in the cooled and acetaminophen-treated groups, respectively.

The results suggest that both delayed hyperthermia and delayed seizures in hyperglycemic animals are caused by the aggravated damage incurred by these animals during or immediately after the ischemic insult.
Cerebroprotective Effect of Lamotrigine After Focal Ischemia in Rats
Authors: Smith Stuart E. , Meldrum Brian S.
Published: June 2011

Background and Purpose
Glutamate receptor antagonists are protective in animal models of focal cerebral ischemia. Lamotrigine (3,5-diamino-6-[2,3-dichlorophenyl]-1,2,4-triazine) is an anticonvulsant drug that blocks voltage-gated sodium channels and inhibits the ischemia-induced release of glutamate. We describe the cerebroprotective effect of lamotrigine (as the isethionate salt) after middle cerebral artery occlusion in rats.

Methods
Neurological deficit and infarct volume (visualized by the lack of reduction of 2,3,5-triphenyltetrazolium chloride) 24 hours after permanent left middle cerebral artery occlusion were studied in Fischer rats (n=8 per group per dose).

Results
Lamotrigine at 20 mg/kg IV over 10 minutes administered immediately after middle cerebral artery occlusion reduced total infarct volume by 31% and cortical infarct volume by 52%. Lamotrigine at 8 mg/kg IV over 10 minutes reduced cortical infarct volume by 38%. Lamotrigine at 50 mg/kg IV for 10 minutes was not cerebroprotective and induced a decrease of 29±15 mm Hg in mean arterial blood pressure (
P
<.05, n=8). The optimum dose of lamotrigine (20 mg/kg IV over 10 minutes) when administered with a 1-hour delay after middle cerebral artery occlusion reduced cortical infarct volume by 41%. Lamotrigine (20 mg/kg IV over 10 minutes) with a 2-hour delay after middle cerebral artery occlusion was ineffective. Neurological deficits after 24 hours were improved after immediate treatment with lamotrigine at 20 mg/kg IV over 10 minutes.

Conclusions
The cerebroprotective effect of lamotrigine in rats is limited to a narrow dose range between 8 and 20 mg/kg. Lamotrigine or analogous compounds may be useful when given shortly after the onset of stroke.
Relation Between Blood Pressure and Outcome in Intracerebral Hemorrhage
Authors: Dandapani Bhuvaneswari K. , Suzuki Shuichi , Kelley Roger E. , Reyes-Iglesias Yolanda , Duncan Robert C.
Published: June 2011

Background and Purpose
Controversy continues to exist regarding optimal blood pressure control in acute hypertensive intracerebral hemorrhage. Persistent marked elevation of the blood pressure can promote further bleeding, increase cerebral blood flow, and raise intracranial pressure. Relative hypotension, on the other hand, may promote hypoperfusion with secondary ischemia. This study was designed to assess outcome in patient groups defined by the degree of elevation in their pretreatment and posttreatment blood pressures.

Methods
We retrospectively assessed 87 patients who were categorized according to an initial mean arterial pressure >145 mm Hg (n=34) compared with those with a pressure ≤145 mm Hg (n=53). We also studied blood pressure control within the first 2 to 6 hours of presentation with subjects categorized according to a mean arterial pressure >125 mm Hg (n=40) or ≤125 mm Hg (n=47).

Results
An improved outcome in both mortality and severe morbidity was observed in the ≤145 (χ
2
=7.0,
P
<.005) and the ≤125 mm Hg (χ
2
=6.7,
P
<.005) groups.

Conclusions
Markedly elevated blood pressure on admission and persistent inadequate blood pressure control adversely affect the prognosis in hypertensive intracerebral hemorrhage.
Isolated Systolic Hypertension and Risk of Stroke in Japanese-American Men
Authors: Petrovitch Helen , Curb J. David , Bloom-Marcus Ellen
Published: June 2011

Background and Purpose
This article examines prevalence of isolated systolic hypertension (ISH) in a population of Japanese-American men living in Hawaii and compares rates of stroke among those with ISH, isolated diastolic hypertension (IDH), combined systolic/diastolic hypertension (SDH), and nonhypertension.

Methods
Eight thousand six men aged 45 to 68 years participated in a baseline examination as part of a prospective study of coronary heart disease and stroke and were followed up for 20 years for incident disease and total mortality. Men were divided into four groups according to baseline blood pressure: ISH (systolic blood pressure [SBP] ≥160 mm Hg and diastolic blood pressure [DBP] <90 mm Hg); IDH (SBP <160 mm Hg and DBP ≥90 mm Hg); SDH (SBP ≥160 mm Hg and DBP ≥90 mm Hg); and nonhypertension (SBP <160 mm Hg and DBP <90 mm Hg).

Results
Men with ISH had the highest rates of stroke, followed by men with SDH. Men with IDH had rates only slightly higher than men in the nonhypertension group. Relative risk adjusted for other risk factors varied by age group. For men aged 45 to 54 years, relative risks of stroke associated with ISH, IDH, and SDH compared with nonhypertensive subjects were 4.8, 1.4, and 4.3, respectively. For men aged 55 to 68 years, the same relative risks were 1.2, 1.8, and 1.7. Excluding men on antihypertensive medication at baseline did not alter results.

Conclusions
ISH had a much greater impact on risk of stroke in younger than in older men. The results suggest that while ISH is more common in older men, in younger men it is associated with higher relative risk of stroke.
Recent Alcohol Consumption, Cigarette Smoking, and Cerebral Infarction in Young Adults
Authors: Hillbom Matti , Haapaniemi Helena , Juvela Seppo , Palomäki Heikki , Numminen Heikki , Kaste Markku
Published: June 2011

Background and Purpose
The role of recent heavy drinking of alcohol as a risk factor for ischemic brain infarction is unclear. We investigated this problem in young adults, in whom even a thorough workup often fails to reveal any predisposing factor.

Methods
This was a hospital-based case-control study comprising 75 consecutive subjects aged 16 to 40 years with first-ever ischemic brain infarction and 133 control subjects from the same hospital who were group-matched with the case patients for age, sex, day of the onset of symptoms, and acuteness of disease onset.

Results
Multiple logistic regression analysis showed that alcohol intake exceeding 40 g of ethanol within the 24 hours preceding disease onset was a significant independent risk factor for brain infarction among both men (odds ratio [OR], 6.0; 95% confidence interval [CI], 1.8 to 20.3) and women (OR, 7.8; 95% CI, 1.0 to 60.8). Cigarette smoking was not found to be an independent risk factor in the model, whereas among men arterial hypertension was (OR, 6.2; 95% CI, 1.5 to 24.7).

Conclusions
We conclude that very recent alcohol drinking, particularly drinking for intoxication, may trigger the onset of brain infarction in young adults and that there might be a variety of mechanisms behind this effect.
Hemodynamic Effects of Carotid Endarterectomy by Magnetic Resonance Flow Quantification
Authors: Vanninen Ritva , Koivisto Keijo , Tulla Harri , Manninen Hannu , Partanen Kaarina
Published: June 2011

Background and Purpose
Blood flow can be evaluated noninvasively using magnetic resonance phase-contrast flow quantification. The purpose of this prospective study was to assess the feasibility of this method and to evaluate the hemodynamic effects of carotid endarterectomy.

Methods
Volumetric flow rates and peak systolic velocities of the internal and common carotid and the vertebral arteries were measured by magnetic resonance flow quantification. Sixteen patients undergoing 18 endarterectomies had complete flow data recorded preoperatively and 3 days after surgery.

Results
The inverse correlation between the angiographic stenosis degree and the preoperative flow rate in the corresponding internal carotid artery was highly significant (
r
=−.69,
P
<.001). After endarterectomy, the mean flow in the ipsilateral internal carotid artery improved from 143 to 233 mL/min (
P
<.001). The mean peak systolic velocity increased from 23 to 37 cm/s (
P
<.001). No significant changes were seen in the contralateral carotid or the vertebral arteries. The mean total blood flow improved by 81 mL/min (
P
=.08). In the severely stenosed bifurcations (70% to 99%, n=11), the flow rate improved by 106 mL/min and in the moderately (30% to 69%, n=4) or mildly (<30%, n=3) stenosed bifurcations by 63 mL/min. If the contralateral carotid artery was occluded or severely stenosed, the improvement was 164 mL/min.

Conclusions
Magnetic resonance flow quantification provides a useful tool for the follow-up of the hemodynamic effects of carotid endarterectomy. Our results indicate that surgery is followed by a significant increase of blood flow in the ipsilateral carotid artery and that there appear to be differences in flow increase between subgroups of patients with different degrees of stenosis.
Accuracy and Prognostic Consequences of Ultrasonography in Identifying Severe Carotid Artery Stenosis
Authors: Eliasziw M. , Rankin R.N. , Fox A.J. , Haynes R.B. , Barnett H.J.M.
Published: June 2011

Background and Purpose
The accuracy of routine ultrasonography in detecting severe carotid artery stenosis was evaluated in comparison with cerebral angiography. The precision of ultrasonographic criteria in predicting the risk of stroke was also assessed.

Methods
A total of 1011 symptomatic carotid bifurcations were studied in patients from the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Given that all patients were considered for entry into the trial, the chance of a verification bias affecting the analyses was minimized. The ultrasonographic data consisted of peak systolic velocities and frequency changes from both the internal and common carotid arteries. Angiographic stenosis was calculated as in NASCET. Receiver operating characteristic (ROC) curves were constructed from the ultrasonographic data for the detection of 70% or greater stenosis on the basis of an angiographic assessment. Kaplan-Meier stroke-free survival curves were used to predict the risk of stroke.

Results
The areas under the ROC curves ranged from 0.74 to 0.75 (95% confidence interval [CI], 0.69 to 0.79). The sensitivities and specificities ranged from 0.65 to 0.71. The risk of stroke at 18 months declined sharply as the degree of angiographically defined stenosis declined from 99% to 70%. No pattern of decline was apparent on the basis of the ultrasonographic data.

Conclusions
The results indicate that the accuracy of ultrasonography is moderate when flow parameters are used to assess the degree of stenosis. Ultrasonography should be used as a screening tool to exclude patients with no carotid artery disease from further testing. Conventional angiography remains an essential investigation before assigning the risk of stroke and deciding appropriate treatment for extracranial carotid artery disease.
Alcohol Consumption and Stroke Mortality
Authors: Hansagi Helen , Romelsjö Anders , de Verdier Maria Gerhardsson , Andréasson Sven , Leifman Anders
Published: June 2011

Background and Purpose
Since stroke is a principal cause of death in elderly people, we analyzed the association between alcohol and stroke mortality in a cohort of 15 077 middle-aged and older men and women.

Methods
Data on alcohol habits were obtained from a questionnaire in 1967. The subsequent 20 years yielded 769 deaths from stroke, of which 574 were ischemic. Relative mortality risks (RR) were estimated from logistic regression analyses with lifelong alcohol abstainers as a reference group. Adjustments were made for age and smoking.

Results
No association was found between alcohol intake and hemorrhagic stroke. An elevated risk of ischemic stroke was found for men who drank infrequently, that is, a few times a year or less often (RR, 2.0; 95% confidence interval [CI], 1.3 to 3.2), for those who were intoxicated now and then (RR, 1.8; 95% CI, 1.1 to 2.8), and for those who reported “binge” drinking a few times in the year or less often (RR, 1.6; 95% CI, 1.1 to 2.5). Among women only ex-drinkers had an elevated risk of dying of ischemic stroke (RR, 3.3; 95% CI, 1.5 to 7.2). The risk was reduced for women who had an estimated average consumption of 0 to 5 g pure alcohol per day (RR, 0.6; 95% CI, 0.5 to 0.8); for those who did not drink every day (RR, 0.7; 95% CI, 0.5 to 0.9); and for those who never “went on a binge” (RR, 0.6; 95% CI, 0.5 to 0.8) or became intoxicated (RR, 0.7; 95% CI, 0.5 to 0.9).

Conclusions
Drinking habits were associated only with deaths from ischemic stroke, and the risk patterns were different for men and women. In analyses, ex-drinkers should not be included with lifelong abstainers, since the former tend to run high health risks.
Incidence and Prognosis of Stroke in the Belluno Province, Italy
Authors: Lauria Giuseppe , Gentile Manrico , Fassetta Giuliano , Casetta Ilaria , Agnoli Fabrizio , Andreotta Giovanni , Barp Claudio , Caneve Giorgio , Cavallaro Alessandro , Cielo Roberto , Mongillo Domenico , Mosca Massimiliano , Olivieri PierGiorgio
Published: June 2011

Background and Purpose
We sought to register the incidence rate, risk factors, and case-fatality rate of all the new cases of first-ever-in-a-lifetime stroke in the province of Belluno, Italy. This study aimed to provide an epidemiological survey of cerebrovascular disease that could supply investigative objectives and support information for regional healthcare facilities planning.

Methods
We undertook a prospective population-based study in the territory of the 1st, 2nd, 3rd, and 4th local health units in the province of Belluno, an area located in northeast Italy (population, 211 389).

Results
In the first year of the study (June 1, 1992, to May 31, 1993), 474 cases of first-ever stroke were registered. The crude annual incidence rate was 2.24/1000 (2.01/1000 for men and 2.45/1000 for women). After adjustment to the European population, the incidence rate for first stroke was 1.70/1000 per year. The pathological diagnosis was confirmed by a CT scan in 89.5% of cases. Cerebral infarction accounted for 319 cases, while 93 patients suffered a primary intracerebral hemorrhage, 12 patients a subarachnoid hemorrhage, and 50 patients a stroke of unknown origin. The overall 30-day case-fatality rate was 33%, and the mortality within the first week from stroke onset was 23%. The recurrence rate after 1 month was 1.9%. After 1 month, 46% of our patients were functionally independent in activities of daily living.

Conclusions
Our first-year results confirm the fairly high risk for stroke in central and northern Italy and support European findings regarding risk factors for stroke.
Postprandial and Orthostatic Cardiovascular Changes After Acute Stroke
Authors: Robinson T.G. , Potter J.F.
Published: June 2011

Background and Purpose
Large falls in blood pressure after meals have been demonstrated in fit and frail elderly subjects; these changes may be associated with an increased incidence of stroke. Postprandial falls in BP may be particularly deleterious after acute stroke, when normal baroreflex mechanisms and cerebral autoregulation are already impaired, resulting in stroke progression. Therefore, the postprandial hemodynamic responses to orthostasis were examined in nine acute stroke subjects and eight age-, sex-, and blood pressure–matched control subjects after an oral energy load.

Methods
All subjects were studied on two occasions in a randomized, double-blind, crossover trial after administration of either oral glucose (1 g/kg body wt) or equivalent isovolumic, isosmotic xylose (0.83 g/kg). Measurements of blood pressure, pulse rate, and forearm blood flow were recorded for 30 minutes preprandially and 90 minutes postprandially. Hemodynamic responses to 60° tilt, along with plasma glucose and insulin changes, were measured at baseline and at 30-minute intervals postprandially.

Results
Supine mean arterial and diastolic blood pressures fell significantly after glucose but not xylose ingestion in control subjects (
P
<.03) but not stroke subjects, whereas supine pulse rate increased in stroke subjects (
P
<.04) only. No significant changes in forearm vascular resistance were recorded in either control or stroke subjects. After tilt, stroke subjects showed a fall in mean arterial pressure compared with control subjects preprandially (
P
=.03) and at 30 (
P
<.005) and 90 (
P
<.03) minutes postprandially, although no differences were observed between the xylose and glucose phases. Orthostatic tolerance was maintained in control subjects throughout both phases of the study. Pulse rate increased significantly to tilt at all time intervals in both groups, although there were no significant changes in forearm vascular resistance.

Conclusions
Acute stroke subjects are not at significantly greater risk of blood pressure falls in response to an oral energy load than age-, sex-, and blood pressure–matched control subjects. Unlike control subjects, the stroke group had an increased pulse rate postprandially, which could result in a compensatory rise in cardiac output as a result of increased sympathetic nervous system activity in the poststroke period. Although orthostatic blood pressure control is impaired after acute stroke, these changes are unaffected by meals.
Costs of Medical Care After First-Ever Stroke in the Netherlands
Authors: Bergman Liesbeth , van der Meulen Jan H.P. , Limburg Martien , Habbema J. Dik F.
Published: June 2011

Background and Purpose
Stroke causes high morbidity and mortality. The aging of the population further increases the demands on healthcare costs.

Methods
We estimated the lifetime direct costs of care of first-ever stroke patients in the Netherlands in 1991 using epidemiological data from national and international studies. In addition, we examined the effect of an aging population on future healthcare costs.

Results
The lifetime costs for 24 007 first-ever stroke patients are estimated to be 1870 million Dutch guilders (Dfl) (1 Dfl=0.53 US dollar, 1991). Per-person costs are higher for women (83 000 Dfl) than for men (71 000 Dfl). The major cost component of first-year costs is hospital costs (45%), while nursing home costs dominate lifetime costs (50%). An increase of the elderly population older than 65 years of 27% between 1991 and 2010 might lead to a parallel increase of total costs of 30%, or 1.5% per year.

Conclusions
Long-term care rather than acute care dominates the lifetime costs for stroke patients now and in the future.
Inositol Trisphosphate, Polyphosphoinositide Turnover, and High-Energy Metabolites in Focal Cerebral Ischemia and Reperfusion
Authors: Sun G.Y. , Zhang J.-P. , Lin T.A. , Lin T.-N. , He Y.Y. , Hsu C.Y.
Published: June 2011

Background and Purpose
Although the signaling pathway involving polyphosphoinositide (poly-PI) hydrolysis and release of inositol 1,4,5-trisphosphate [Ins(1,4,5)P
3
] is an important mechanism for regulation of neuronal calcium homeostasis, the effect of cerebral ischemia-reperfusion on this calcium signaling pathway is not well understood. Because activity of this pathway is dependent on availability of ATP, this study is aimed at examining the poly-PI signaling pathway and high-energy metabolites in a rat stroke model.

Methods
Focal cerebral ischemia in rats was induced by temporary occlusion of the right middle cerebral artery and both common carotid arteries. Levels of Ins(1,4,5)P
3
were determined by use of the radioreceptor binding assay. Poly-PI turnover in rat cortex was assessed with an in vivo protocol involving intracerebral injection of [
3
H]inositol and systemic administration of lithium. High-energy metabolites (ATP, ADP, and AMP) were analyzed by high-performance liquid chromatography.

Results
Ischemia induced an increase in poly-PI turnover in the right middle cerebral artery cortex, but reperfusion led to a decline in this signaling activity. However, Ins(1,4,5)P
3
levels decreased during ischemia, and these levels were not restored if ischemic insults were longer than 30 minutes. ATP levels decreased to 26% of control during ischemia and recovered to 80% of control during the initial 4 hours of reperfusion; these changes were followed by a second phase of decline.

Conclusions
Results show an important relationship between ischemia-induced depletion of high-energy metabolites and poly-PI signaling activity. However, the uncoupling between Ins(1,4,5)P
3
and ATP during reperfusion after severe ischemia suggests that metabolism of Ins(1,4,5)P
3
is more stringently regulated than ATP.
Spontaneous Thrombosis of an Unruptured Anterior Communicating Artery Aneurysm
Authors: Brownlee Richard D. , Tranmer Bruce I. , Sevick Robert J. , Karmy Grigory , Curry Bernadette J.
Published: June 2011

Background
Stroke caused by spontaneous thrombosis of an unruptured intracranial aneurysm is a rare event.

Case Description
A 66-year-old woman experienced a transient ischemic attack and cerebral infarctions due to spontaneous thrombosis of an unruptured anterior communicating artery aneurysm. Extension of thrombus into both anterior cerebral arteries and the left middle cerebral artery, resulting in ischemic infarction in all three vascular territories, was diagnosed by CT scanning, MRI, and cerebral angiography and confirmed at autopsy.

Conclusions
This case illustrates a rare complication of an unruptured saccular aneurysm with neuroimaging and pathological correlation. Morphological and hemodynamic factors that may have precipitated aneurysm thrombosis are discussed with reference to experimental models.
Evidence for Cardioembolic Stroke in a Case of Kearns-Sayre Syndrome
Authors: Kosinski Christoph , Mull Michael , Lethen Harald , Töpper Rudolf
Published: June 2011

Background
Cerebral infarction is a known complication in patients with mitochondrial encephalomyopathies (MELAS, MERRF, Kearns-Sayre syndrome), but the etiology in the different types remains uncertain.

Case Description
A 33-year-old woman who had suffered from ophthalmoplegia, bilateral ptosis, ataxia, retinitis pigmentosa, and epilepsy since childhood was diagnosed to have Kearns-Sayre syndrome. The diagnosis was confirmed by muscle biopsy when she was 17 years old. A pacemaker was implanted because of the occurrence of bradyarrhythmias when she was 24 years old. The patient was admitted to the hospital with left-sided hemiparesis of sudden onset due to right striatocapsular infarction. Results of Doppler sonography of the carotid arteries were normal; however, transesophageal echocardiography revealed a thrombus in the left atrial appendage.

Conclusions
Stroke in Kearns-Sayre syndrome is likely to be due to cardiac embolism. Anticoagulant therapy should be considered even for mild forms of cardiomyopathies leading to left ventricular dysfunction.
Acute Fatal Deterioration in Putaminal Hemorrhage
Authors: Wijdicks Eelco F.M. , Fulgham Jimmy R.
Published: June 2011

Background
Clinical deterioration in patients with spontaneous intracerebral hemorrhage has rarely been studied. It has been previously thought that intracranial hematomas bleed in a monophasic fashion. Recent studies have demonstrated continuous active bleeding within hours after the event, resulting in enlargement of the hematoma. However, acute sudden and fatal deterioration suggesting a rebleed is rarely reported.

Summary of Reports
An 84-year-old man was admitted with a moderate-size hemorrhage in the putamen and was treated for hypertension during the first day of admission. He acutely demonstrated extensor posturing and light-fixed pupils. Repeat CT scan showed massive enlargement of the intracranial hematoma and extension into the ventricles causing acute hydrocephalus. A 72-year-old man was admitted with a mid-size hemorrhage in the putamen. Acute deterioration with loss of all brain stem reflexes except for cornea reflexes was associated with a large increase in volume of the hematoma, 7 hours after the initial hemorrhage. An 85-year-old woman was admitted with a small hemorrhage in the putamen and recovered to be able to walk unassisted. She suddenly died from a recurrent massive putaminal hemorrhage 2 weeks after the ictus.

Conclusions
Patients with spontaneous intracerebral hemorrhage in the putamen may die acutely from fatal catastrophic enlargement of the initial hematoma hours to days after the ictus. In some patients with spontaneous intracerebral hemorrhage and clinical deterioration, rebleeding may be a possible mechanism.
A Model to Predict the Histopathology of Human Stroke Using Diffusion and T2-Weighted Magnetic Resonance Imaging
Authors: Welch K.M.A. , Windham Joseph , Knight Robert A. , Nagesh Vijaya , Hugg James W. , Jacobs Mike , Peck Donald , Booker Patty , Dereski Mary O. , Levine Steven R.
Published: June 2011

Background and Purpose
We sought to identify MRI measures that have high probability in a short acquisition time to predict, at early time points after onset of ischemia, the eventual development of cerebral infarction in clinical patients who suffer occlusion of a cerebral artery.

Methods
We developed an MR tissue signature model based on experimentally derived relationships of the apparent diffusion coefficient of water (ADC
w
) and T
2
to ischemic brain tissue histopathology. In eight stroke patients we measured ADC
w
and T
2
intensity using diffusion-weighted echo-planar imaging (DW-EPI). Tissue signature regions were defined, and theme maps of the ischemic focus at subacute time points after stroke onset were generated.

Results
Five MR signatures were identified in human stroke foci: two that may predict either cell recovery or progression to necrosis, one that may mark the transition to cell necrosis, and two that may be markers of established cell necrosis.

Conclusions
An MR tissue signature model of ischemic histopathology using ADC
w
and T
2
can now be tested for its potential to predict reversible and identify irreversible cellular damage in human ischemic brain regions.
Stroke In China, 1986 Through 1990
Authors: Cheng Xue-Ming , Ziegler Dewey K. , Lai Yen-Huei C. , Li Shi-Chuo , Jiang Guo-Xing , Du Xiao-Li , Wang Wen-Zhi , Wu Sheng-Ping , Bao Su-Ge , Bao Qiu-Ju
Published: June 2011

Background and Purpose
Incidence of stroke varies markedly in different world populations. In seven Chinese cities, the effect of a program of risk factor modification on the incidence and mortality of stroke was studied and compared with a control population. This article describes the incidence of stroke in the control populations for the years 1986 through 1990.

Methods
Incidence (first-ever strokes only) for 1986 was obtained by door-to-door interview with heads of households with subsequent verification on examination by a neurologist and review of medical and/or hospital records. In subsequent years, cases were ascertained with a three-tier monitoring system: by community health workers, local medical centers, and the Beijing Neurosurgical Institute.

Results
Average annual age-adjusted incidence per 100 000 was 215.6 (261.5 for males, 174.5 for females;
P
<.001). There was a significant drop in the total number of cases from 137 in 1986 to 106 in 1990, but the age-adjusted rate showed a significant drop for males only (322.3 to 182.5,
P
<.001). Marked differences in average annual age-adjusted rates existed among the seven cities, from 486.4 for Harbin to 80.9 for Shanghai. This difference in rate among cities was found for both sexes but was more pronounced in males.

Conclusions
The stroke incidence rates in China, like those in Japan, are among the higher ones in the world. In recent years, there has been an apparent decline in stroke incidence. Marked differences in rates were found between males and females with decline in incidence occurring almost exclusively in males. There were also marked differences in stroke incidence among the cities studied. These differences may result in part from differences in diet, alcohol and cigarette consumption, or prevalence of hypertension.
Phase I: Transcranial Echo Contrast Studies in Healthy Volunteers
Authors: Kaps Manfred , Schaffer Peter , Beller Klaus-Dieter , Seidel Günther , Bliesath Harald , Wurst Wilhelm
Published: June 2011

Background and Purpose
Transcranial ultrasound diagnostics are particularly hindered by insufficient ultrasound penetration through the temporal bone. The use of ultrasonic contrast media to enhance the Doppler signal is an important step toward the solution of this problem. In the present study we investigated the tolerability and the diagnostic value of a new intravenous transpulmonary ultrasonic contrast medium, BY963.

Methods
In two phase I studies, 8 healthy volunteers received a spherosome suspension containing a phospholipid as the active ingredient. The intravenous injection was performed in three doses (2.5, 5, and 10 mL) at four different injection rates (0.25, 0.5, and 1 mL/s and bolus). The duration and degree of the signal enhancement were measured by two transcranial ultrasonic procedures presently used in clinical practice: transcranial Doppler sonography (TCD) and transcranial color-coded sonography (TCCS). The assessment of tolerability was based on chemical laboratory parameters and hemodynamic data (heart rate, blood pressure, electrocardiogram) and on questionnaires relating to general well-being.

Results
BY963 was tolerated without complications. All 38 administrations of the echo contrast medium produced a marked increase in the TCD signal (>30 dB) in the intracranial basal cerebral arteries. To obtain the optimum time window for diagnostic use, higher doses with slower injection rates are advantageous. The duration of optimal contrasting was 42 to 68 seconds (TCD) and 12 to 132 seconds (TCCS), depending on the method and mode of administration. Bolus injections gave rise to an increased incidence of color artifacts.

Conclusions
BY963 significantly improves intracranial Doppler imaging while being well tolerated. The signal enhancement lasts long enough for TCCS to display all basal cerebral arteries after just one injection.
Induction of Cerebral Thrombosis With Phenytoin in Rats
Authors: Tani Shigeru , Shimizu Takashi , Kasuya Hidetoshi , Iwasaki Hitoshi , Takashima Kohki
Published: June 2011

Background and Purpose
This study was conducted to explore whether intra-arterial infusion of phenytoin causes cerebral ischemia and to examine the mechanism of cerebral ischemia induced by phenytoin.

Methods
Ten rats were infused with phenytoin (150 μL, 3.75 mg) retrogradely from the left external carotid artery, followed by perfusion of carbon black transcardially. The removed brain was photographed from above, and the nonperfused area was compared with control rats (n=10) with the use of an image analyzer. Eight animals with or without phenytoin treatment were perfusion-fixed for transmission electron microscopic analyses of cerebral vasculature. To determine the effect of tissue plasminogen activator (TPA) on phenytoin-infused rat cerebrum, 20 rats were treated with or without TPA (120 000 IU) 5 minutes after the phenytoin infusion (n=10 each).

Results
All rats suffered from respiratory distress 25 to 40 minutes after the injection and received carbon black transcardially. The nonperfused area was seen in the territory of the left internal carotid artery. Thrombi were observed from arterioles to capillaries. Under electron microscopy, endothelial cells were partially exfoliated, and the vascular lumen was obstructed by thrombi predominantly consisting of platelets. Eight rats with TPA survived more than 60 minutes, whereas only 2 rats survived without the treatment (
P
<.005). Nonperfused areas were 7±5% and 50±11% of cerebral surface area in rats with and without TPA treatment, respectively (
P
<.001).

Conclusions
Intra-arterial infusion of phenytoin results in a nonperfused area in rat cerebrum primarily due to thrombosis of arterioles and capillaries.
A Reproducible Model of Middle Cerebral Infarcts, Compatible with Long-term Survival, in Aged Rats
Authors: Wang LiJuan C. , Futrell Nancy , Wang David Z. , Chen Fang-Jie , Zhai Qi-hui , Schultz Lonni R.
Published: June 2011

Background and Purpose
Stroke is a disease associated with aging, but experimental stroke studies are generally done in young male animals. Because there are numerous differences associated with aging, such as an altered immune system and altered neurochemistry, that could affect the outcome of these experiments, a model of reproducible cerebral infarction in aged rats is needed.

Methods
We attempted to produce middle cerebral artery (MCA) infarcts in aged (22 months of age) rats using two standard methods. A nylon suture with a heat-induced bulb was passed through the external carotid artery in seven animals, with an attempt to place the tip at the origin of the MCA. The MCA was ligated through a craniotomy just proximal to the internal cerebral vein in 14 rats. Survival potential was tested by attempting 2-week survival in four rats and 2-month survival in one rat.

Results
The suture model failed to produce MCA infarcts, even when the bulb of the suture was properly placed in the MCA. The intracranial MCA occlusion resulted in reproducible MCA infarcts. There were no deaths, including the animals allowed to survive 2 weeks and 2 months.

Conclusions
We conclude that reproducible MCA infarcts can be produced in aged rats by craniotomy and that these lesions may be compatible with long-term survival. This should be a useful technique for studying therapeutic interventions and rehabilitation strategies in an animal model that immunologically and neurochemically more closely resembles humans at risk for stroke.
Sequential Studies of Severely Hypometabolic Tissue Volumes After Permanent Middle Cerebral Artery Occlusion
Authors: Touzani Omar , Young Alan R. , Derlon Jean-Michel , Beaudouin Vincent , Marchal Gilles , Rioux Patrice , Mézenge Florence , Baron Jean-Claude , MacKenzie Eric T.
Published: June 2011

Background and Purpose
In the positron emission tomography literature, markedly hypometabolic brain tissue (oxygen metabolism <1.3 to 1.7 mL · 100 g
−1
· min
−1
) has often been equated with irreversible damage in the human brain. By serial positron emission tomography measurements, we investigated the temporal evolution of the volume of severely hypometabolic brain tissue after permanent middle cerebral artery occlusion in anesthetized baboons with, as a perspective, the development of rational therapeutic strategies.

Methods
Seven anesthetized and ventilated baboons underwent sequential positron emission tomography examinations with the
15
O steady-state technique before and 1, 4, 7, and 24 hours and 14 to 29 days after occlusion. In each baboon the infarct volume was calculated by quantitative histological procedures after 19 to 41 days of occlusion.

Results
The sequential measurement of regional oxygen metabolism demonstrated an extension (for ≥24 hours) of the volume of severely hypometabolic tissue as defined by both absolute and relative metabolic thresholds, and this profile of evolutivity is observed no matter the threshold used. Mean (±SEM) infarction volume of 2.4±0.6 cm
3
was comparable to a tissue volume with oxygen consumption <40% of contralateral metabolism. The volume of hypometabolic tissue was essentially stable at the 1-, 4-, and 7-hour postocclusion studies, increased markedly at the 24-hour study point, and increased even further in the chronic-stage study (on average, 17 days after occlusion). The tissue that eventually displayed a severely hypometabolic state at the final measurement showed a significant decrease of oxygen metabolism and cerebral blood flow at each time analyzed. In that tissue, the oxygen extraction fraction increased significantly at 1 hour (although not thereafter).

Conclusions
The extension of severely hypometabolic volume after middle cerebral artery occlusion reinforces the concept of a dynamic penumbra and suggests the existence of a relatively large window of therapeutic opportunity in which it may be possible to develop neuroprotective strategies. Our study suggests that maximum infarct volume is determined at some time between 24 hours and 17 days after permanent middle cerebral artery occlusion in anesthetized baboons.
Neocortical Neural Sprouting, Synaptogenesis, and Behavioral Recovery After Neocortical Infarction in Rats
Authors: Stroemer R. Paul , Kent Thomas A. , Hulsebosch Claire E.
Published: June 2011

Background and Purpose
Neuroanatomical plasticity is well described in lesions of the hippocampus but remains a subject of some controversy in the neocortex. The purpose of the present study was to measure the neocortical distribution and density of expression of proteins known to be involved in neurite growth or synaptogenesis and to correlate the neocortical expression with behavioral recovery after a focal neocortical infarction. Focal neocortical infarction creates a circumscribed lesion in the neocortex that provides a denervation stimulus for neurite growth and synaptogenesis.

Methods
Unilateral neocortical ischemia was induced in male spontaneously hypertensive Wistar rats (n=4 per time point) by permanent occlusion of the distal middle cerebral artery and ipsilateral common carotid artery. To determine the spatial and temporal distribution of neurite growth and/or synaptogenesis, GAP-43, a growth-associated protein expressed on axonal growth cones, and synaptophysin, a calcium-binding protein found on synaptic vesicles, were examined by immunohistochemical techniques. The reaction product was measured, and the distribution was recorded. Since the resulting infarction included a portion of the forelimb neocortex, behavioral assessments of forelimb function that used the foot-fault test of Hernandez and Schallert were performed on the same rats used for immunohistochemical studies. Recovery times were 3, 7, 14, 30, and 60 days after surgery.

Results
Both GAP-43 and synaptophysin proteins demonstrated statistically significant increases in the density of immunoreaction product as determined by optical density measurements in the neocortex of infarcted rats compared with sham controls. The GAP-43 was elevated to statistically significant levels in forelimb, hindlimb, and parietal neocortical regions medial and lateral to the infarction only at days 3, 7, and 14. In contrast, synaptophysin demonstrated no statistically significant changes in expression at 3 or 7 days but demonstrated statistically significant increases at 14, 30, and 60 days in the forelimb, hindlimb, and parietal neocortical regions medial and lateral to the infarction as well as in the contralateral parietal neocortex. Behavioral assessment of forelimb function indicated impairment of forelimb placement on the side contralateral to the infarction that trended toward control values at 14 days and was not significantly different from controls by 30 days.

Conclusions
These data support the occurrence of neurite growth followed by synaptogenesis in the neocortex, ipsilateral and contralateral to neocortical ischemia, in a pattern that corresponds both spatially and temporally with behavioral recovery. Thus, neuroanatomical remodeling in the neocortex provides a mechanism for recovery of function.
Widespread Appearance of Alz-50 Immunoreactive Neurons in the Human Brain With Cerebral Infarction
Authors: Uchihara Toshiki , Tsuchiya Kuniaki , Kondo Hiromi , Hayama Tadayoshi , Ikeda Kenji
Published: June 2011

Background and Purpose
Tau-like immunoreactivity is known to develop in neurons under some experimental conditions simulating ischemia. The purpose of this study is to investigate the expression of tau-like immunoreactivity in the human brain after ischemic insult.

Methods
A series of autopsied human brains with or without ischemic lesion were investigated with immunohistochemistry (Alz-50, anti-tau, and anti-ubiquitin) and with silver-staining methods (Gallyas and Bodian methods).

Results
Punctate immunoreactivity to Alz-50 was visualized in the cytoplasm not only of the neurons in and around the ischemic lesion but also of the neurons free from classic ischemic changes around the necrosis. Some of the neurons around the ischemic lesion were stained by the Gallyas method. Immunostaining with anti-tau and anti-ubiquitin antibodies and the conventional Bodian method failed to visualize these neurons.

Conclusions
The widespread appearance of Alz-50 immunoreactive neurons during the ischemic process signifies that tau-related proteins may be related to ischemic necrosis, but the lack of neurofibrillary tangles morphologically distinguishes ischemic development of tau-related proteins from the neurofibrillary degeneration in Alzheimer’s disease.
7-Nitroindazole Inhibits Brain Nitric Oxide Synthase and Cerebral Vasodilatation in Response to
N
-Methyl-
d
-aspartate
Authors: Faraci Frank M. , Brian Johnny E.
Published: June 2011

Background and Purpose N
-Methyl-
d
-aspartate (NMDA) produces dilatation of cerebral arterioles that is dependent on production of nitric oxide (NO). In these experiments we examined the hypothesis that cerebral vasodilatation in response to NMDA is mediated by the neuronal isoform of NO synthase.

Methods
We measured diameters of cerebral arterioles (baseline diameter, 89±7 μm) using a closed cranial window in anesthetized rabbits that received either vehicle (10 mL/kg IP peanut oil) or 7-nitroindazole (7-NI; 50 mg/kg IP). 7-NI is reported to be a selective inhibitor of neuronal NO synthase.

Results
Two hours after administration of 7-NI, activity of brain NO synthase (measured by conversion of
l
-arginine to
l
-citrulline) was reduced by 33% compared with vehicle (24±1 versus 16±3 pmol/min per milligram protein; n=7;
P
<.05). Dilatation of cerebral arterioles in response to NMDA (100 and 300 μmol/L) was inhibited by 30% to 40% by 7-NI compared with responses in the presence of vehicle (23±6% versus 14±5% and 30±4% versus 21±5%, respectively;
P
<.05 for both concentrations; n=10). In contrast, vasodilatation in response to acetylcholine (1 μmol/L) was similar in vehicle- and 7-NI–treated animals (17±5% versus 21±4%;
P
>.05).

Conclusions
These findings suggest that vasodilatation in response to NMDA is mediated by neuronally derived NO. 7-NI appears to produce selective inhibition of brain NO synthase but not endothelial NO synthase.
Massive Persistent Release of Excitatory Amino Acids Following Human Occlusive Stroke
Authors: Bullock R. , Zauner A. , Woodward J. , Young H.F.
Published: June 2011

Background
Animal stroke models demonstrate excitatory amino acid (EAA) release in ischemic tissue, as measured by microdialysis. Currently glutamate antagonist drugs are being developed to protect brain tissue after ischemic events. However, the role of EAAs in human occlusive stroke is not well known. We therefore measured glutamate and aspartate release in a patient after occlusive stroke.

Case Description
We describe a case of occlusive stroke in a 50-year-old man. A partial temporal lobectomy was done to remove infarcted tissue and to prevent brain stem compression as well as uncal herniation. A microdialysis probe was placed into the cortex to measure EAAs. Massively increased levels of glutamate and aspartate were detected in the extracellular fluid in this patient (>300 times normal levels 6 days after infarction).

Conclusions
These findings indicate that EAAs are tremendously increased in brain tissue after occlusive stroke. The time course of the release of EAAs is much longer than animal studies have suggested previously. Administration of EAA antagonists to patients with ischemic stroke may therefore be beneficial.