bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Emergency Department Management of Stroke in Houston, Texas
Authors: Bratina P. , Greenberg L. , Pasteur W. , Grotta J. C.
Published: June 2011

Background and Purpose
This study describes emergency department (ED) management of stroke in Houston, Tex, in 1992 to identify delays and deficiencies in recognition and management of stroke patients in various hospital subtypes and to quantitate the impact of a rapid response stroke team.

Methods
ED logs of eight hospitals were retrospectively screened, and 112 patients with suspected acute stroke onset within 6 hours were identified. EDs were divided into four groups based on hospital size (175 to 979 beds), acuity, number of stroke admissions (50/y to 210/y), and availability of neurological consultations. The intervals from stroke onset to triage, examination by a physician, neurological evaluation, computed tomography (CT) and other tests, vital signs, and treatments were recorded.

Results
The average time from stroke to ED arrival was 115 minutes, and times from ED arrival to examination by a physician and CT scan were 28 and 100 minutes, respectively, with little variability among hospital groups except that the public hospital was slower. Neurological examinations were poorly documented in community and public hospitals. The presence of a stroke team shortened the time to examination by a physician and to CT by 13 and 63 minutes, respectively, and increased the number of patients admitted to the intensive care unit. Blood pressure was excessively lowered in 31% of hypertensive patients, and hypotonic dextrose intravenous fluids were given to 69% of all patients.

Conclusions
Transport, initial evaluation, and ED care of acute stroke patients are currently slow and often inexpert in all types of hospitals. A stroke team can speed initial ED management.
Effect of Intracarotid Administration of 6-Aminonicotinamide on Cerebral Blood Flow in Cats
Authors: Kuchiwaki Hiroji , Inao Suguru , Yoshida Kazuo , Sugita Kenichiro
Published: June 2011

Background and Purpose
We evaluated the effects of an adenosine triphosphate blocker, 6-aminonicotinamide (6-ANA), on the cerebral blood flow (CBF), cerebral metabolism, and electroencephalogram of cats.

Methods
Catheters were inserted into the common carotid artery of 16 adult cats anesthetized with ketamine via the lingual artery. We measured CBF in the infused area by the inhaled hydrogen gas clearance method and analyzed the electroencephalogram frequency. Cerebral metabolism was estimated by oxygen extraction (vol/%) and glucose utilization (millimoles) using data arterial (aorta) and sagittal sinus blood samplings. A solution of 6-ANA (6.0 mg/mL) (n=8) or saline (n=8) was infused via catheter at 2.0 mL/min for 3 minutes followed by a 60-minute observation of CBF, cerebral metabolism, vascular resistance, and the electroencephalogram components, alpha-2 ratio [=alpha-2/(alpha-1+alpha-2)]. The effect of 6-ANA on capillaries was evaluated by extravasation of Evans blue dye and electron microscopic findings.

Results
Moderate reductions in CBF, cerebral metabolism, and the alpha-2 ratio were observed during the infusion of 6-ANA versus saline infusion (
P
<.05 by paired
t
test and ANOVA). Vascular resistance was significantly increased (
P
<.05). No abnormalities were observed in the capillaries of the infused hemisphere.

Conclusions
Results indicated that 6-ANA produced a downregulation of cerebral blood flow in cats.
Interleukin-1 as a Pathogenetic Mediator of Ischemic Brain Damage in Rats
Authors: Yamasaki Yasundo , Matsuura Naosuke , Shozuhara Hidetaka , Onodera Hiroshi , Itoyama Yasuto , Kogure Kyuya
Published: June 2011

Background and Purpose
It has been suggested that interleukin-1 (IL-1) is a potent inflammatory mediator and that it is synthesized and secreted into the brain parenchyma. The aim of the present study is to evaluate the contribution of IL-1 to brain edema formation after focal brain ischemia.

Methods
The brain water content was measured to evaluate postischemic brain injury in rats after 60 minutes of middle cerebral artery occlusion and reperfusion. The effects of exogenous application of recombinant human interleukin-1β (rhIL-1β), anti–interleukin-1β neutralizing antibodies (anti–IL-1β), and the IL-1 blocker zinc protoporphyrin (ZnPP) on brain water content were observed, and histological technique was used to measure the infarction size and number of inflammatory cells infiltrated into the brain.

Results
Transient ischemia induced marked increase of brain water content, necrosis, and neutrophilic infiltration in the cortex perfused by the middle cerebral artery and the dorsal and ventral areas of the caudate putamen. Injection of rhIL-1β into the left lateral ventricle immediately after reperfusion markedly enhanced ischemic brain edema formation in these three areas in a dose-dependent manner (88.4±0.7% and 86.6±0.4% in the dorsal and ventral parts of the caudate putamen, respectively, in rats treated with 10 ng rhIL-1β;
P
<.01). rhIL-1β also increased the size of the brain infarction, and it tended to increase the number of infiltrating neutrophils in ischemic areas and the number of neutrophils adherent to the endothelium. In contrast, administration of anti–IL-1β and ZnPP into the left cerebral ventricle attenuated the postischemic increase of brain water content and decreased the size of brain infarction (83.5±2.0% and 79.9±2.0% in the dorsal and ventral parts of the caudate putamen, respectively, in rats treated with 10 μg anti–IL-1β;
P
<.01). The number of neutrophils that infiltrated into ischemic areas also tended to decrease with anti–IL-1β or ZnPP treatment.

Conclusions
Application of rhIL-1β augmented the increase of brain water content, and application of anti–IL-1β depressed the increase of water content. These results tended to correlate with the neutrophilic infiltration into the parenchyma. It thus appears that IL-1β may play an important role in ischemic brain damage after reperfusion.
Fatal Infantile Polyarteritis NodosaWith Predominant CentralNervous System Involvement
Authors: Engel D. G. , Gospe S. M. , Tracy K. A. , Ellis W. G. , Lie J. T.
Published: June 2011

Background
Infantile polyarteritis nodosa usually presents in children under 2 years of age as a multiorgan system disease with signs of congestive heart failure or renal failure. This disease and Kawasaki disease may share certain clinical and pathological features.

Case Description
We describe a child who first presented at 8 months of age with a febrile illness followed by a delay in motor and language development and a mild right hemiparesis. Five years later he died after developing oculomotor dysfunction, hypertension, and intracranial hemorrhage. Autopsy revealed focal segmental necrotizing vasculitis of cerebral arteries, without involvement of coronary or renal vessels.

Conclusions
Although this child was evaluated on several occasions during this time period, the diagnosis was not made antemortem. The predominant central nervous system features, both clinical and pathological, together with the prolonged course are the two unique features of this child’s disease that need to be emphasized.
Hemiplegia Vegetativa Alterna (Ipsilateral Horner’s Syndrome and Contralateral Hemihyperhidrosis) Following Proximal Posterior Cerebral Artery Occlusion
Authors: Bassetti Claudio , Staikov Ivan N.
Published: June 2011

Background
Posterior cerebral artery (PCA) occlusive disease usually produces homonymous visual field defects, hemisensory loss, and neuropsychological deficits. Conversely, the combination of hemiparesis, Horner’s syndrome, and contralateral hemihyperhidrosis has never been reported before.

Case Description
A patient with infarction in the superficial and deep territories of the right PCA presented with a unique clinical picture, which included contralateral hemiparesis, hemihyperhidrosis, and ipsilateral Horner’s syndrome. Magnetic resonance imaging disclosed infarcts in the right anterolateral midbrain, ventroposterolateral thalamic-subthalamic area, and temporo-occipital lobes.

Conclusions
The alternating vegetative syndrome (hemiplegia vegetativa alterna) observed in this patient supports the hypothesis of the existence of an uncrossed excitatory and a crossed inhibitory hypothalamospinal sympathetic pathway.
Nonfasting Serum Glucose and the Risk of Fatal Stroke in Diabetic and Nondiabetic Subjects
Authors: Håheim L. Lund , Holme I. , Hjermann I. , Leren P.
Published: June 2011

Background and Purpose
The association between nonfasting serum glucose and stroke mortality for diabetic and nondiabetic subjects is presented for participants of the Oslo Study.

Methods
The study started in 1972; of 16 209 men aged 40 to 49 years, 16 172 had no previous history of stroke and 151 were known to be diabetic. Five diabetic and 80 nondiabetic subjects died of stroke during the 18 years of follow-up, giving a rate ratio of 7.87 (95% confidence interval [CI], 2.48 to 19.14). The rate of mortality for all causes in diabetic subjects was more than five times that of those who were nondiabetic.

Results
Nonfasting serum glucose was a predictor of fatal stroke in all participants (diabetic subjects included) without a history of stroke in age-adjusted univariate analysis. The relative risk was 1.13 (CI, 1.03 to 1.25) by increase of 1 mmol/L of serum glucose according to results of proportional hazards regression analysis. Accordingly, relative risk for nondiabetic subjects was 1.02 (CI, 0.83 to 1.26) with no linear trend. The rate ratio of the fifth quintile to the rest was 1.57 (CI, 0.94 to 2.56) for all participants and 1.28 (CI, 0.72 to 2.18) for nondiabetics.

Conclusions
There was an interaction between glucose level and body mass index versus stroke for all participants but not for nondiabetic subjects, with an increased risk for men with above-median values of glucose and body mass index. Analysis of nondiabetic subjects failed to show glucose as a definite predictor of fatal stroke.
Alterations of Brain Levels of Phosphoinositidase-C–Linked Gqα/G11α Proteins and Motor Function in Rats After Cardiac Arrest
Authors: Jaw Shyhwen P. , Su Duan D. , Matsumoto Rae R. , Truong Daniel D.
Published: June 2011

Background and Purpose
Phosphoinositidase-C–linked G
qα
and G
11α
proteins have only recently been characterized. Second messenger systems are known to be affected by hypoxia-ischemia. However, the effects of hypoxia-ischemia on the brain levels of G
qα
and G
11α
proteins are not known. Therefore, in the present studies, the effects of hypoxia-ischemia on G
qα
and G
11α
proteins in rats were investigated with quantitative immunoblot analysis.

Methods
Cardiac arrest was induced in male Sprague-Dawley rats by an intracardial injection of KCl. Resuscitation began 10 minutes afterwards. At various time points after resuscitation, animals were killed and the cerebral cortex, striatum, and cerebellum were dissected. Levels of G
qα
and G
11α
proteins were investigated by quantitative immunoblot analysis.

Results
At 1, 2, 4, and 6 hours after resuscitation, G
qα
and G
11α
protein levels remained unaltered. However, a significant reduction of these proteins was seen in the cerebral cortex and cerebellum of rats 3 and 14 days after cardiac arrest, with partial recovery by an average of 60 days. In contrast, no significant change was detected in the striatum.

Conclusions
These observations indicate that phosphoinositidase-C–linked signal transduction pathways may be attenuated after hypoxic-ischemic insults to the brain, and that this phenomenon, together with many other factors, may contribute to the expression of motor dysfunction in rats after cardiac arrest.
Chronic Depression of Glucose Metabolism in Postischemic Rat Brains
Authors: Beck Thomas , Goller Hans-Joachim , Wree Andreas
Published: June 2011

Background and Purpose
The present investigation aimed to quantify functional activity in rat brains after long-term recovery from transient forebrain ischemia.

Methods
With the use of the [
14
C]2-deoxyglucose method, local cerebral glucose utilization was measured in 62 cortical and subcortical brain regions in postischemic rat brains. Transient forebrain ischemia of 10 minutes’ duration was induced by clamping the common carotid arteries and simultaneously lowering blood pressure to 40 mm Hg. Rats survived the insults for 1 week, 2 weeks, 3 weeks, or 3 months.

Results
Reductions predominated in the majority of gray matter structures at all time points investigated (
P
<.05). Except for a few areas, recoveries of local cerebral glucose utilization to preischemic levels did not occur.

Conclusions
The data illustrate that widespread alterations of functional activity prevail in postischemic brains beyond the selectively vulnerable regions. The present functional data are in line with previous stereological results of reduced fresh volumes in the majority of postischemic brain structures. The data suggest that chronic alterations of ischemic brains are not confined to the selectively vulnerable regions.
Community-Based Stroke Incidence Trends From the 1970s Through the 1980s in East Germany
Authors: Eisenblätter Dorothea , Heinemann Lothar , Claßen Elvira
Published: June 2011

Background and Purpose
Stroke mortality has declined in most industrialized countries, but incidence rates have increased in some populations while they remained stable or even decreased in others. This study reports stroke incidence trends in East Germany over the past decades.

Methods
Prospective community-based stroke registers were run in East Germany over two different time periods: 1972 through 1973 in the Berlin-Lichtenberg district and 1985 through 1988 in 14 districts in the central and southern part of the country. Stroke cases were collected and validated in a uniform way using both the World Health Organization (WHO) recommendations for community stroke registers and the guidelines of the WHO MONICA protocol.

Results
Annual age-adjusted incidence rates of first-ever strokes rose among men aged 25 to 64 years from 48.4 per 100 000 in 1972 through 1973 to 88.0 per 100 000 in 1985 through 1988 (
P
<.05); incidence rates remained unchanged among women in this age range (52.6 and 52.5 per 100 000, respectively). Age-specific incidence rates increased among men in all age groups up to 74 years. Rising stroke rates were also observed in women under 55 years and between the ages of 65 and 74 years, whereas in women aged 55 to 65 years incidence rates declined by more than a third (
P
<.05). During the period from 1985 through 1988, stroke rates did not change.

Conclusions
An increase in stroke incidence was detected that can be associated with a deteriorating risk factor profile in the East German population and, in particular, with hypertension in men.
Is the Stroke Belt Disappearing?
Authors: Howard George , Evans Gregory W. , Pearce Kevin , Howard Virginia J. , Bell Ronny A. , Mayer Elizabeth J. , Burke Gregory L.
Published: June 2011

Background and Purpose
The stroke risk among white residents of the coastal plain of North Carolina, South Carolina, and Georgia (the “Stroke Belt”) has been reported to be between 1.3 and 2.0 times the national average. In this study we examined (1) whether a similar excess risk exists for blacks in this region, (2) whether this regional excess stroke risk has decreased over time, and (3) whether the regional excess risk is consistent across ages from 45 to more than 85 years.

Methods
Using data from the Compressed Mortality File, we estimated the annual relative stroke mortality risk for black and white men and women in a region of 153 coastal plain counties and compared these rates to those for the remainder of the United States.

Results
The relative geographic excess risk of stroke death was similar for black residents and white residents of the Stroke Belt for both men and women. Despite the decline in stroke mortality, the relative increased risk of stroke death in the region has remained constant from 1968 to 1991; however, the pattern of excess risk across age differed significantly between race/sex groups.

Conclusions
These data show that the Stroke Belt continues to exist for blacks and whites and for men and women. Although the specific causes of the Stroke Belt remain unknown, the public health impact is staggering, with a greater than 40% excess risk of stroke mortality and more than 1200 excess stroke deaths annually.
Serum Folate and Risk for Ischemic Stroke
Authors: Giles Wayne H. , Kittner Steven J. , Anda Robert F. , Croft Janet B. , Casper Michele L.
Published: June 2011

Background and Purpose
A serum folate concentration ≤9.2 nmol/L has been associated with elevated levels of plasma homocyst(e)ine. Elevated homocyst(e)ine levels have been associated with ischemic stroke in case-control studies; however, the results from prospective studies have been equivocal. We investigated whether a folate concentration ≤9.2 nmol/L was associated with ischemic stroke in a national cohort.

Methods
We used data from the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (n=2006). Cox proportional hazards analyses were used to adjust for differences in follow-up time and covariates. During the 13-year follow-up, 98 ischemic strokes occurred.

Results
After adjusting for age, race, sex, education, diabetes, history of heart disease, systolic blood pressure, body mass index, hemoglobin level, cigarette smoking, and alcohol intake, participants with a folate concentration ≤9.2 nmol/L were at slightly increased risk for ischemic stroke (relative risk [RR], 1.37; 95% confidence interval [CI], 0.82 to 2.29). There was a folate-race interaction (
P
=.11 for interaction term). Whites with a folate concentration ≤9.2 nmol/L had a relative risk of 1.18 (95% CI, 0.67 to 2.08), whereas blacks had a relative risk of 3.60 (95% CI, 1.02 to 12.71).

Conclusions
These findings suggest that a folate concentration ≤9.2 nmol/L may be a risk factor for ischemic stroke, especially in blacks. However, given the small number of stroke events, additional studies are needed to assess the role of folate in the epidemiology of ischemic stroke.
Routine Use of Limited Abdominal Aortography With Digital Subtraction Carotid and Cerebral Angiography
Authors: Hans Sachinder Singh , Zeskind H. Jay
Published: June 2011

Background and Purpose
We sought to evaluate the usefulness of limited abdominal aortography performed in conjunction with intra-arterial carotid digital subtraction arteriography (DSA) for identification of clinically unsuspected lesions.

Methods
In a prospective study performed in the Department of Radiology after preliminary carotid duplex imaging, 401 consecutive bilateral carotid intra-arterial DSAs were performed for evaluation of cerebrovascular disease from June 1988 to November 1992.

Results
We detected unilateral renal artery stenosis in 24 patients (6%), bilateral renal artery stenosis in 5, renal cell carcinoma in 1, renal artery aneurysm in 1, abdominal aortic aneurysm in 23 (5.7%), aortic ectasia in 16, and iliac aneurysm in 2.

Conclusions
When single-plane digital abdominal aortography is performed in conjunction with carotid intra-arterial DSA, significant pathological lesions can be detected with little increase in morbidity and only modest increase in time and cost.
Delayed Antagonism of Calpain Reduces Excitotoxicity in Cultured Neurons
Authors: Brorson James R. , Marcuccilli Charles J. , Miller Richard J.
Published: June 2011

Background and Purpose
Glutamate receptor antagonists can produce protection against the neurotoxicity of excessive glutamate stimulation. However, antagonism of the postreceptor processes that produce cell damage may provide a longer window of opportunity for protecting neurons after the initiation of excitotoxic injury. Among various processes that have been thought to mediate the toxic effects of glutamate are activation of the Ca
2+
-dependent proteases calpain I and II and the activation of nitric oxide synthase. We tested the potential for neuroprotection by delayed application of calpain antagonists after excitotoxic treatment.

Methods
Primary cultures of cerebellar and hippocampal neurons were exposed to the glutamate receptor agonists kainate and
N
-methyl-
d
-aspartate (NMDA) for 20-minute periods, and survival was examined by fluorescent assay after 24 hours. Enzyme antagonists were applied at various time points during this interval.

Results
The neurotoxic effects of NMDA in cultured hippocampal neurons and of kainate in cultured cerebellar neurons have been previously shown to be Ca
2+
dependent. Here we show that in both of these examples of glutamate receptor–mediated toxicity, activation of a calpainlike proteolytic activity occurred, which was blocked by the calpain inhibitor MDL-28170. This inhibitor also limited the toxicity, even when applied at times up to 1 hour after the onset of the toxic exposure. Another protease inhibitor, E-64, also blocked the proteolysis and toxicity produced by kainate in cerebellar neurons. Blocking nitric oxide synthase activity after 1 hour with the antagonist
N
G
-nitro-
l
-arginine was also protective of cerebellar and hippocampal neurons, as was the combination of MDL-28170 and
N
G
-nitro-
l
-arginine.

Conclusions
The activation of calpain is among several enzymatic processes that contribute to the toxicity of glutamate receptor stimulation, and blocking these postreceptor mechanisms can be effective in protecting neurons from excitotoxicity at delayed time points.
M1 Receptors in Blood Pressure–Controlled Ischemic Spontaneously Hypertensive Rats
Authors: Hirata Hiroshi , Asanuma Masato , Tanaka Ken-ichi , Kondo Yoichi , Ogawa Norio
Published: June 2011

Background and Purpose
Hypertension is a primary aggravating factor in cerebral infarction. An acute rise in blood pressure (BP) at the time of a stroke may be harmful to the brain in a hypertensive subject because both cerebral vascular structure and function are altered by hypertension. Muscarinic M
1
receptors are concerned with memory and learning. We aimed to evaluate the effect of controlling BP in hypertensive subjects at the time of stroke with a biochemical index of brain damage.

Methods
We gave a single dose of either the antihypertensive α-blocker phentolamine (2 mg/kg IP) or the calcium antagonist nicardipine (2 mg/kg IP) at the start of bilateral carotid artery occlusion to spontaneously hypertensive rats undergoing 3 hours of transient ischemia; we measured the time course of mean BP (MBP) and changes in the M
1
receptor and its mRNA in three brain regions 2 weeks after the transient ischemia.

Results
Administration of phentolamine or nicardipine not only significantly suppressed the ischemia-induced rise of MBP, it actually decreased MBP during ischemia. In an ischemic control group, M
1
receptor binding decreased in the frontal cortex and M
1
receptor mRNA increased in the hippocampus 2 weeks after the ischemia. In contrast, both phentolamine- and nicardipine-treated ischemic rats showed no changes in either index compared with sham-operated controls.

Conclusions
Controlling BP during an ischemic insult attenuates ischemia-induced damage of M
1
receptors in the brain of spontaneously hypertensive rats. These results suggest that a rapid intensive increase of BP at the time of a stroke may exacerbate brain damage in hypertensive individuals.
Temporal Patterns of Stroke Onset
Authors: Kelly-Hayes Margaret , Wolf Philip A. , Kase Carlos S. , Brand Frederick N. , McGuirk Jacqueline M. , D’Agostino Ralph B.
Published: June 2011

Background and Purpose
Several studies have shown stroke onset to vary by season, day of the week, and time of day. These temporal patterns, which may provide insights into pathogenesis, were found mainly in clinical series, which can be subject to selection bias. To obtain a less distorted picture of stroke onset, we examined the month and season, day of the week, time, and place stroke occurred in a community-based cohort.

Methods
Over a 40-year period of surveillance of the Framingham Study cohort of 5070 people aged 30 to 62 years and free of stroke and cardiovascular disease at entry, 637 completed initial strokes occurred. Month, season, day of the week, time of day, and place of occurrence of stroke were ascertained systematically and related prospectively to stroke incidence, subtype, and gender.

Results
Winter was the peak season for cerebral embolic strokes. Significantly more stroke events occurred on Mondays than any other day, particularly for working men. For intracerebral hemorrhages, a third happened on Mondays in both genders. The time of day when strokes most frequently occurred was between 8
am
and noon. This pattern was true for all stroke subtypes. This pattern persisted when individuals whose onset occurred while sleeping or on awakening were excluded. Stroke in general occurred more at home, with hemorrhagic strokes occurring outside the home and cerebral embolisms in the hospital more than other subtypes.

Conclusions
Temporal patterns of stroke onset were observed for season, day of the week, time of day, and place in a community-based population. These findings suggest that there are periods of increased risk of stroke that may be amenable to preventive strategies.
Nocturnal Blood Pressure Dip in Stroke Survivors
Authors: Nakamura Kensei , Oita Jiro , Yamaguchi Takenori
Published: June 2011

Background and Purpose
The influence of a nocturnal blood pressure dip on stroke recurrence has not yet been clarified. In this pilot study, we attempted to establish a correlation of the nocturnal blood pressure dip with stroke recurrence and development of new silent ischemic lesions in patients with chronic ischemic cerebrovascular disease.

Methods
We monitored circadian blood pressure patterns by use of a portable blood pressure monitoring device in 81 patients with chronic ischemic cerebrovascular disease and divided them into two subgroups according to levels of diurnal and nocturnal blood pressure (nocturnal blood pressure dippers and nondippers). The subgroups were prospectively followed up and compared for stroke recurrence and new silent ischemic lesions on magnetic resonance imaging.

Results
The average follow-up period was 27.2±11.3 months (mean±SD). Seventy-six patients completed the study; 43 (36 men and 7 women, aged 63.0±6.3 years) were being treated with antihypertensive agents and 33 (25 men and 8 women, aged 64.7±9.2 years) were not receiving treatment. In the treated group, recurrence was more frequent among the nocturnal dippers (5 of 18 patients, 12.5% per patient-year) than among the nondippers (1 of 25 patients, 1.5% per patient- year) (
P
<.05). All subjects who developed a recurrent attack during sleep had had a nocturnal blood pressure dip pattern before the attack. Furthermore, the increase in symptomatic (recurrence) and/or asymptomatic (silent) brain lesions was more frequent in the nocturnal dippers than in the nondippers (9 of 14 versus 2 of 18,
P
<.01). In the nontreated group, no clear difference was found between the two subgroups.

Conclusions
This study indicated that the nocturnal blood pressure dip in patients treated with antihypertensive agents may accelerate the increase in ischemic brain lesions.
Circulation of Red Blood Cells Having High Levels of 2,3-Bisphosphoglycerate Protects Rat Brain From Ischemic Metabolic Changes During Hemodilution
Authors: Kimura Hideo , Hamasaki Naotaka , Yamamoto Masaaki , Tomonaga Masamichi
Published: June 2011

Background and Purpose
We designed the present study to examine the effects of red blood cell oxygen-delivering capacity on ischemic brain metabolism during hemodilution with respect to red blood cell 2,3-bisphosphoglycerate content.

Methods
A modification of red blood cell 2,3-bisphosphoglycerate content was achieved by an exchange transfusion of blood in which red blood cells were treated with either phospho(enol)pyruvate or inorganic phosphate in spontaneously hypertensive rats. Hematocrit values of circulating blood were varied from 30% to 20% during transfusion. Brain ischemia was produced in rats by bilateral carotid artery occlusion lasting 60 minutes. The concentrations of ATP and 2,3-bisphosphoglycerate in the blood and the ATP, phosphocreatine, and lactate concentrations in the brain were estimated by an enzymatic method.

Results
Red blood cell 2,3-bisphosphoglycerate concentration increased to 200% of the pretransfusion level after the transfusion in which red blood cells were treated with phospho(enol)pyruvate, whereas the concentration decreased to 80% after the transfusion in which red blood cells were treated with phosphate. Red blood cell ATP content did not differ significantly between the phospho(enol)pyruvate- and phosphate-treated groups after transfusion. When hematocrit was approximately 30%, the ischemic brain ATP and lactate contents did not differ between the nonischemic and ischemic groups. However, as hematocrit was reduced to less than 25% the ischemic brain ATP content remarkably decreased and the lactate content substantially increased in the 2,3-bisphosphoglycerate–subnormal red blood cell group. In contrast, the ischemic brain ATP and phosphocreatine contents in the 2,3-bisphosphoglycerate–enriched red blood cell group were preserved and as high as those in the nonischemic group under the same conditions.

Conclusions
Cerebral ischemia was compensated with the increment of cerebral blood flow as a result of the reduction of hematocrit to optimal levels, but the extreme hemodilution induced insufficient oxygen supply to the brain tissue, resulting in a more marked impairment of brain metabolism despite an increase in cerebral blood flow. However, even in extreme hemodilution conditions the 2,3-bisphosphoglycerate–enriched red blood cells in circulating blood protected the brain from ischemic metabolic changes. These results suggest that the 2,3-bisphosphoglycerate–enriched red blood cells in the circulating blood may thus compensate for the insufficient oxygen supply in extremely anemic conditions by providing a sufficient supply of oxygen in the face of ischemic insult.
Ischemic Stroke as First Manifestation of Essential Thrombocythemia
Authors: Arboix Adrià , Besses Carles , Acín Pilar , Massons Juan B. , Florensa Lourdes , Oliveres Montserrat , Sans-Sabrafen Jordi
Published: June 2011

Background
Ischemic stroke as a presenting sign of essential thrombocythemia has been infrequently reported. We describe six patients in whom cerebrovascular disease was the first manifestation of this myeloproliferative disease. A positive endogenous megakaryocyte and/or erythroid colony growth from blood was a diagnostic criterion of essential thrombocythemia in patients with platelets counts lower than 600×10
9
/L.

Case Descriptions
These six patients represented 0.54% of all patients with first stroke, 42.8% of all hematologic disorders associated with stroke, and 12.5% of all patients with essential thrombocythemia diagnosed from 1986 to 1992 at our institution. Eleven acute cerebrovascular accidents (6 transient ischemic attacks, 5 definitive cerebral infarcts) were registered. Mean time from ischemic stroke to diagnosis of essential thrombocythemia was 4.5 months (range, 1 to 12 months). The mean platelet count was 597×10
9
/L (range, 414 to 760×10
9
/L). Four patients had platelets counts lower than 600×10
9
/L. All patients had circulating erythroid progenitors, megakaryocytic progenitors, or both.

Conclusions
Ischemic stroke as a presenting manifestation of essential thrombocythemia is probably underrecognized. The diagnosis of thrombocythemia should not be excluded on the basis of platelet counts lower than 600×10
9
/L. The availability of in vitro culture of hematopoietic progenitors from peripheral blood makes it possible to diagnose early and atypical cases.
Induction of c-
fos
and c-
jun
Gene Products and Heat Shock Protein After Brief and Prolonged Cerebral Ischemia in Gerbils
Authors: Takemoto Osamu , Tomimoto Hidekazu , Yanagihara Takehiko
Published: June 2011

Background and Purpose
Proto-oncogene activation and induction of heat shock protein (HSP) occur in response to various stimuli to brain, but the role in neuronal survival after cerebral ischemia remains uncertain. We compared the extent of insults and induction of c-
fos
and c-
jun
gene products (c-FOS and c-JUN) as well as HSP in ischemic and postischemic gerbil brains immunohistochemically.

Methods
Common carotid arteries of Mongolian gerbils were occluded for 5 or 15 minutes and recirculated for 0 minutes to 7 days. Antibodies for c-FOS, c-JUN, and HSP 70 were used for immunohistochemistry, and positive reactions were semiquantitatively analyzed. The presence of ischemic and postischemic lesions was ascertained with an antibody for microtubule-associated proteins.

Results
After ischemia for 15 minutes and reperfusion, c-FOS was induced promptly after 1 to 6 hours in pyramidal cells of the CA3 and CA4 regions, while c-JUN became visible in the same areas after recirculation for 4 to 48 hours. HSP 70 was detected after recirculation for 24 hours in the CA3 region. In layers I and II of the cerebral cortex, c-FOS and c-JUN peaked at 3 hours and HSP 70 at 96 hours. Induction of these proteins was absent or negligible in the areas that developed ischemic or postischemic lesions, including the subiculum-CA1 and CA1 regions of the hippocampus and layers III/IV and Vb/VI of the cerebral cortex. After shorter ischemia for 5 minutes and reperfusion, c-FOS and c-JUN were rapidly induced at 15 minutes to 1 hour except for the subiculum-CA1 and CA1 regions of the hippocampus. Induction of HSP 70 did not occur for 24 hours and was noted only in the hippocampus.

Conclusions
Induction of c-FOS and c-JUN occurred in the areas surviving after transient cerebral ischemia, but the extent of induction and the latent period varied depending on the duration of the insult and the location. In the areas with ischemic or postischemic damage detected by loss of the reaction for microtubule-associated proteins, the induction of c-FOS and c-JUN was either absent or minimal, suggesting that active induction of those immediate early gene products occurred early in surviving neurons. On the other hand, the induction of HSP 70 did not occur until reperfusion for 24 hours and actively occurred only in the areas with earlier induction of c-FOS and/or c-JUN, suggesting that the induction of HSP 70 occurred in neurons that survived to that point, but it did not participate in early responses for neuronal survival after global cerebral ischemia.
Demonstration of Increased Endothelial-Leukocyte Adhesion Molecule–1 mRNA Expression in Rat Ischemic Cortex
Authors: Wang Xinkang , Yue Tian-Li , Barone Frank C. , Feuerstein Giora Z.
Published: June 2011

Background and Purpose
Leukocyte infiltration from circulating blood into ischemic brain tissue contributes significantly to ischemic injury. The role of adhesion molecules in leukocyte attachment and infiltration in ischemic tissue has been emphasized. The aim of the present study was to evaluate whether endothelial-leukocyte adhesion molecule–1 (ELAM-1 or E-selectin) mRNA expression is upregulated in focal brain ischemia.

Methods
Northern blot analysis with the use of poly(A) RNA isolated from the ischemic and nonischemic rat cortex at 2 and 12 hours after permanent occlusion of the middle cerebral artery (PMCAO) was used to examine ELAM-1 mRNA expression. The temporal expression profile of ELAM-1 mRNA in the ischemic cortex was further evaluated with the use of a quantitative reverse transcription and polymerase chain reaction technique.

Results
A very low level of ELAM-1 mRNA was detected in the sham-operated cortex or in the nonischemic cortex. The expression of ELAM-1 mRNA in the focal ischemic cortex was significantly induced by PMCAO, reaching a peak level at 12 hours (6.9-fold increase compared with sham surgery cortical samples,
P
<.01) and remained elevated for up to 2 days (3.3-fold increase,
P
<.01) after PMCAO.

Conclusions
The demonstration of upregulated ELAM-1 mRNA expression after focal stroke suggests that ELAM-1 may play an important role in leukocyte infiltration into the ischemic brain and that ELAM-1 may provide a potential therapeutic target in ischemic stroke. However, the demonstration of translated ELAM-1 and its cellular localization in the ischemic tissue is required when specific antibodies become available.
Comparative Study of Power-Based Versus Mean Frequency-Based Transcranial Color-Coded Duplex Sonography in Normal Adults
Authors: Baumgartner Ralf W. , Schmid Cornelia , Baumgartner Iris
Published: June 2011

Background and Purpose
Power-based transcanial color-coded duplex sonography (p-TCCD) is a new ultrasonic method that has advantages compared with frequency-based TCCD (f-TCCD), since it is essentially independent of the angle of insonation, not subject to aliasing, and has a better signal-to-noise ratio. The purpose of this study was to evaluate the ability of p-TCCD to visualize flow in cerebral parenchyma and to compare the advantages, limitations, and reliability of velocity measurements of p-TCCD versus f-TCCD in the major basal cerebral arteries of normal subjects.

Methods
Two investigators performed 15 p-TCCD and 15 f-TCCD studies in 30 normal subjects with adequate ultrasonic windows. Each investigator did a p-TCCD or f-TCCD study in every patient, and each was blinded in every case to the results of the other. Peak systolic (V
s
) and end-diastolic (V
d
) velocities were determined in the anterior, middle, and posterior cerebral, basilar, and vertebral arteries. The reliability of p-TCCD velocimetry was evaluated by calculating both the correlation coefficient (
r
) of the difference between p-TCCD versus f-TCCD measurements and the coefficient of variation (CV), defined as the difference between the mean values for p-TCCD and f-TCCD divided by the mean values for f-TCCD measurements, expressed as percent.

Results
p-TCCD did not display flow in cerebral parenchyma but depicted arteries with a course perpendicular to that of the ultrasound beam and showed good reliability of velocity measurements in all examined arteries: for V
s
,
r
was .84 to .93 (
P
<.001) and CV was 7.7% to 10.8%; for V
d
,
r
was .87 to .90 (
P
<.001) and CV was 10.3% to 13.7%. The lack of directional and velocity information and tissue motion artifacts were unimportant limitations in p-TCCD.

Conclusions
Compared with f-TCCD, p-TCCD had no important advantages but had several unimportant limitations in a study of normal adults with adequate ultrasonic windows.
Arterial Blood Pressure After Human Cardiac Arrest and Neurological Recovery
Authors: Müllner Marcus , Sterz Fritz , Binder Michael , Hellwagner Klaus , Meron Giora , Herkner Harald , Laggner Anton N.
Published: June 2011

Background and Purpose
In animal cardiac arrest studies, outcome has been improved by inducing arterial hypertension early after return of spontaneous circulation. The aim of our study was to evaluate whether arterial blood pressure within the first minutes and hours after return of spontaneous circulation influences neurological recovery in human cardiac arrest survivors.

Methods
Of 136 retrospectively evaluated patients after sudden cardiac death, two groups were defined: group 1, mean arterial blood pressure (MABP) within 5 minutes after return of spontaneous circulation above 100 mm Hg; group 2, MABP of 100 mm Hg or less. Thereafter MABP was measured every 5 minutes until 2 hours after return of spontaneous circulation. The groups were compared in regard to age, sex, in/out of hospital, witnessed/not witnessed, first electrocardiographic rhythm, time from cardiac arrest to beginning of life support and to return of spontaneous circulation, cumulative epinephrine dose administered, and best neurological outcome within 6 months.

Results
In group 1 (n=54) good neurological recovery was observed in 63% and in group 2 (n=82) in 55% (χ
2
=0.87,
P
=NS). Both groups exhibited comparable baseline values except that time intervals from beginning of life support to return of spontaneous circulation were shorter in group 1. After we controlled for this difference with Spearman’s partial rank correlation (
r
s
), there was no association between MABP measured within the first 5 minutes and outcome (
r
s
=−.023;
P
=NS). Good neurological recovery was independently and directly related to MABP measured during 2 hours after return of spontaneous circulation (
r
s
=.26;
P
<.01).

Conclusions
In human cardiac arrest survivors, good functional neurological recovery was independently and positively associated with arterial blood pressure during the first 2 hours after human cardiac arrest but not with hypertensive reperfusion within the first minutes after return of spontaneous circulation.
Hypertension, Stroke, and Coronary Heart Disease in Relatives of Patients With Subarachnoid Hemorrhage
Authors: Bromberg J.E.C. , Rinkel G.J.E. , Algra A. , van den Berg U.A.C. , Tjin-A-Ton M.L.R. , van Gijn J.
Published: June 2011

Background and Purpose
First-degree relatives of patients with subarachnoid hemorrhage (SAH) have a three to seven times greater risk of SAH than second-degree relatives and than the general population. If hypertension, which is in part genetically determined, contributes to this increased risk, the frequency of hypertension and its sequelae would be expected to be higher in first- than in second-degree relatives of patients with SAH.

Methods
We compared the reported frequency of hypertension, stroke, and coronary heart disease between 1290 first- and 3588 second-degree relatives of a prospective series of patients with SAH.

Results
The relative risk adjusted for age and survival status in first-degree relatives was 2.3 (95% confidence interval [CI], 1.9 to 2.9) for hypertension, 1.8 (95% CI, 1.3 to 2.4) for stroke, and 1.9 (95% CI, 1.5 to 2.3) for coronary heart disease.

Conclusions
Hypertension is a familial factor contributing to the risk of SAH. Hypertension should be sought and treated in first-degree relatives of patients with SAH to reduce the increased risk of cerebrovascular and cardiovascular diseases.
Comparison of Transcranial Doppler Ultrasonography and Transesophageal Echocardiography to Monitor Emboli During Coronary Artery Bypass Surgery
Authors: Barbut D. , Yao F.S. , Hager D.N. , Kavanaugh P. , Trifiletti R.R. , Gold J.P.
Published: June 2011

Background and Purpose
Transcranial Doppler ultrasonography (TCD) is the standard technique for monitoring emboli in the cerebral circulation. Embolic signals have been detected with the use of this technique in most patients undergoing coronary artery bypass surgery. We previously reported that the majority of emboli are detected after release of aortic cross-clamps and partial occlusion clamps. In this study we compare the intraoperative use of TCD with transesophageal echocardiography (TEE) to monitor cerebral emboli.

Methods
We simultaneously monitored 20 patients undergoing coronary bypass surgery with TCD and TEE. All patients also underwent routine TEE examination of the aorta.

Results
Embolic signals were detected in all patients by both techniques. Mean total number of emboli was 535±109 by TEE compared with 133±28 by TCD. We found correlation between numbers of emboli detected by the two techniques at clamp placement and release (
r
=.65,
P
=.002). Clamp placement and release accounted for 84% of all emboli by TEE and 83% by TCD. By TEE, large, highly echogenic particles were detected after clamp release compared with small, barely echo-dense particles at the onset of bypass. No such distinction was apparent by TCD. We found correlation between severity of aortic atheroma and both TEE- (
P
=.003) and TCD-detected (
P
=.009) emboli.

Conclusions
TEE and TCD can both be used to continuously monitor emboli during coronary artery bypass surgery. However, TEE is invasive and justified only if it is being performed for intraoperative assessment of aortic atheromatosis or cardiac function.
Comparison of Neurological Scales and Scoring Systems for Acute Stroke Prognosis
Authors: Muir Keith W. , Weir Christopher J. , Murray Gordon D. , Povey Chris , Lees Kennedy R.
Published: June 2011

Background and Purpose
Clinical trials routinely use stroke scales to compare baseline characteristics of treatment groups. It is unclear which stroke scale provides the most prognostic information. This often leads to collection of multiple scales in clinical trials. We aimed to determine which of several commonly used scales best predicted outcome.

Methods
A single observer scored consecutive admissions to an acute stroke unit on the National Institutes of Health Stroke Scale (NIHSS), the Canadian Neurological Scale, and the Middle Cerebral Artery Neurological Score. Guy's prognostic score was determined from clinical data. Outcome at 2, 3, 6, and 12 months was categorized as good (alive at home) or poor (alive in care or dead). Predictive accuracy of the variables was compared by receiver operating characteristic curves and stepwise logistic regression.

Results
Of the 408 patients studied, 373 had confirmed acute stroke and completed follow-up. The three stroke rating scales each predicted 3-month outcome with an accuracy of .79 or greater. The NIHSS provided the most prognostic information: sensitivity to poor outcome, .71 (95% confidence interval [CI], .64 to .79); specificity, .90 (95% CI, .86 to .94); and overall accuracy, .83 (95% CI, .79 to .87). Logistic regression showed that the NIHSS added significantly to the predictive value of all other scores. No score added useful information to the NIHSS. A cut point of 13 on the NIHSS best predicted 3-month outcome.

Conclusions
Baseline NIHSS best predicts 3-month outcome. The Canadian Neurological Scale and Middle Cerebral Artery Neurological Score also perform well. Baseline assessments in clinical trials only need to include a single stroke rating scale.
Somatosensory Evoked Potentials Correlate With Neurological Outcome in Rabbits Undergoing Cerebral Air Embolism
Authors: Reasoner Daniel K. , Dexter Franklin , Hindman Bradley J. , Subieta Alberto , Todd Michael M.
Published: June 2011

Background and Purpose
Somatosensory evoked potentials (SSEPs) have been used as an outcome measure in models of cerebral air embolism despite the lack of studies correlating SSEPs with other measures of neurological injury. We examined the relationship between SSEPs and neurological impairment in the setting of cerebral air embolism.

Methods
Anesthetized New Zealand White rabbits received either 0, 50, 100, or 150 μL/kg of air into the internal carotid artery. SSEPs were recorded at intervals for the subsequent 2 hours. After the final recording the anesthetic was discontinued, and the animals recovered. Animals were neurologically evaluated at 3 and 24 hours after cerebral air embolism on a scale of zero (normal) to 97 (coma) points.

Results
There was a clear relationship between the dose of air and 2-hour SSEP amplitude (
P
=.00003). SSEP amplitudes at 2 hours were inversely correlated with neurological impairment scores at 3 hours (τ=−0.71,
P
<.0001). SSEP amplitudes at 2 hours were less in animals that died (11±16%; n=9) than in those that survived to 24 hours (53±20%; n=9) (
P
=.0008).

Conclusions
These results support SSEPs as an index of neurological impairment in this model of cerebral air embolism.