bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vivo Studies of Extracellular Metabolites in the Striatum After Distal Middle Cerebral Artery Occlusion in Stroke-Prone Spontaneously Hypertensive Rats
Authors: Shirotani Toshiki , Shima Katsuji , Chigasaki Hiroo
Published: June 2011

Background and Purpose
We demonstrated in a previous study that
45
Ca accumulation in the lateral part of the striatum was detected 3 days after distal middle cerebral artery (MCA) occlusion using a
45
Ca autoradiographic technique in stroke-prone spontaneously hypertensive rats. However, the mechanism of delayed neuronal damage that occurred in the lateral part of the striatum is unknown. We examined changes in amino acids and monoamines in the striatums of rat brains after MCA occlusion in stroke-prone spontaneously hypertensive rats using an in vivo brain microdialysis technique.

Methods
Microdialysis probes were inserted into the lateral or medial part of the striatum 24 hours before the experiment. The dialysis probe was perfused continuously at 2 μL/min with Ringer’s solution, and the dialysate samples were collected every 20 minutes. After a 3-hour period for baseline stabilization, the right MCA was occluded. The dialysate count of monoamines and amino acids was determined by high-performance liquid chromatography.

Results
After MCA occlusion, a threefold transient increase in glutamate was observed in the lateral part of the striatum. The level returned to its baseline value 60 minutes after MCA occlusion. Dopamine in the lateral part increased twofold to its peak value. This release persisted for 2 hours after MCA occlusion. There were no significant changes in these components in the extracellular fluid of the medial part of the striatum.

Conclusions
Our study demonstrated that changes of neurotransmitters in the lateral part of the striatum after MCA occlusion differed from those in the medial part. These results suggest that excessive release of glutamate and dopamine is related to delayed neuronal damage that occurs in the lateral part of the striatum in this model.
Acute Lacunar Stroke in Association With Angiogram-Negative Subarachnoid Hemorrhage
Authors: Tatter Stephen B. , Buonanno Ferdinando S. , Ogilvy Christopher S.
Published: June 2011

Background and Purpose
Although there is much speculation regarding the source of bleeding in patients with subarachnoid hemorrhage when no angiographic abnormality is found, little direct evidence has been obtained to document a cause. We report two cases of stroke in the distribution of a perforating or lenticulostriate artery occurring at the time of angiogram-negative subarachnoid hemorrhage.

Case Descriptions
A 68- and a 60-year-old man each presented with acute onset of headache and meningismus. Computed tomography (CT) revealed subarachnoid hemorrhage in a perimesencephalic pattern and in the left sylvian fissure, respectively. In both instances, immediate CT revealed evidence of an early infarction in the distribution of a perforating artery originating at the site of the subarachnoid blood. Both of these strokes were demonstrated to be acute by evolution on serial imaging studies. No source for the subarachnoid blood could be found in either patient in cerebral angiograms repeated at 2 weeks.

Conclusions
These observations suggest that in some cases of angiogram-negative subarachnoid hemorrhage the source of blood may be a small artery that is obliterated at the time of hemorrhage. This observation provides an explanation for the low rate of rehemorrhage among patients with angiogram-negative subarachnoid hemorrhage.
Transcranial Doppler Ultrasonography in Cerebral Arteriovenous Malformations
Authors: Mast H. , Mohr J. P. , Thompson J. L. P. , Osipov A. , Trocio S. H. , Mayer S. , Young W. L.
Published: June 2011

Background and Purpose
We sought to investigate (1) the sensitivity of transcranial Doppler ultrasonography (TCD) for diagnosis of cerebral arteriovenous malformations (AVMs) and (2) the association of feeding artery flow velocity profiles with spontaneous hemorrhage and focal neurological deficit in AVM patients.

Methods
We examined 114 consecutive AVM patients prospectively by TCD; 22 non-AVM patients with acute cerebral hemorrhage and 52 normal subjects served as controls. To estimate the association of blood flow velocity patterns in feeding arteries with spontaneous hemorrhage and focal neurological deficit, the total group of AVM subjects was divided into patients with and without a history of bleeding and also into those with and without clinical signs of “steal” (focal deficit unrelated to hemorrhage).

Results
Sensitivity for large and medium-sized AVMs was high (>80%), whereas 62% of small AVMs were missed. TCD was also highly sensitive (80%) in a group of five AVM patients with acute hemorrhage. Flow velocity profiles were not related to spontaneous hemorrhage (mean velocity, 111 cm/s in patients with hemorrhage versus 114 cm/s in patients without hemorrhage;
P
=.65) or clinical signs of steal (mean velocity, 111 cm/s versus 113 cm/s in patients with and without steal, respectively;
P
=.89).

Conclusions
We concluded that (1) TCD is highly sensitive for large and medium-sized AVMs; (2) in acute cerebral hemorrhage TCD may help to differentiate AVM from non-AVM bleeds; (3) the predictive value of TCD findings for clinical sequelae of AVMs remains undetermined; and (4) the concept of hemodynamic steal in AVMs is not supported by TCD data.
Intravenous Aspirin Causes a Paradoxical Attenuation of Cerebrovascular Thrombolysis
Authors: Thomas G. Roger , Thibodeaux Harold , Errett Carol J. , Bednar Martin M. , Gross Cordell E. , Bennett William F.
Published: June 2011

Background and Purpose
Aspirin treatment is recognized as an advantageous adjunct to thrombolytic agents in myocardial infarct patients. In this study we examined the effects of aspirin on the rate of clot lysis and on the frequency and extent of hemorrhagic transformations in rabbit models of embolic stroke.

Methods
Rabbit models of ex vivo platelet aggregation and cutaneous template bleeding times were used to show the anticoagulant effects of aspirin in our experimental paradigm. We monitored tissue-type plasminogen activator (TPA)–induced clot lysis in two rabbit models of embolic stroke by (1) scintigraphically following the dissolution of a
99m
Tc-tagged clot or (2) using roentgenography to follow the disappearance of an Sn-tagged clot.

Results
In animals pretreated (18 hours) with a single administration of aspirin (1, 5, or 20 mg/kg IV) or 1 mg/kg per day for 3 days, the aggregation response of platelets to collagen (3.3 μg/mL) or arachidonic acid (0.5 mmol/L) was attenuated. High-dose aspirin also increased ear template bleeding time from 1.6 to 2.6 minutes. When aspirin (20 mg/kg) was administered 18 hours before embolism and subsequent lysis with TPA (0.3 mg/kg bolus; 3 mg/kg per hour IV), the pretreatment significantly antagonized the rate and extent of TPA-induced clot lysis by up to 70%. This was confirmed in a second embolic stroke model. The suppression of TPA-induced lysis was reversed by administration of the prostacyclin analogue iloprost (10 μg/kg per hour) directly into the cerebral circulation.

Conclusions
We conclude that aspirin reduces the effects of TPA in embolic stroke models. This effect may be the result of a loss of endothelial prostacyclin production since the effect is reversed by iloprost.
Silent Cerebral Infarctions in Patients With Late-Onset Mania
Authors: Fujikawa Tokumi , Yamawaki Shigeto , Touhouda Yoshikuni
Published: June 2011

Background and Purpose
Previously we have studied the relationship between senile depression and silent cerebral infarctions (SCIs). The goal of this study was to clarify the relationship between late-onset mania and SCIs using MR imaging.

Methods
Twenty manic patients who developed a bipolar disorder after 50 years of age (late-onset mania) were selected prospectively. These patients were compared with 20 age- and sex-matched patients who developed an affective disorder while younger than 50 years of age (early-onset affective disorder) and with 20 patients who developed major depression after 50 years of age (late-onset major depression). Patients with focal neurological symptoms were excluded from the study. All patients underwent MR imaging to assess the incidence of SCIs. Patients diagnosed with SCIs were subclassified according to whether the infarction type was perforating, cortical, or mixed.

Results
The incidence of SCIs in patients with late-onset mania was 65.0%; this incidence was significantly higher than that of patients with early-onset affective disorders (
P
<.05). The incidence of the mixed type of SCI was 50.0% in patients with late-onset mania; this was significantly higher than that in patients with late-onset major depression (
P
<.05).

Conclusions
Our findings suggest that approximately half of the cases of late-onset mania might be secondary mania related to SCIs. Because the mixed type of SCI is more prevalent in the patients with late-onset mania than in those with late-onset major depression, mania may be associated with the larger areas of brain damage and hence may be a more serious form of affective illness than major depression.
Thalamic Hemorrhage
Authors: Kumral Emre , Kocaer Tülay , Ertübey Nese Özgen , Kumral Kamuran
Published: June 2011

Background and Purpose
The clinical features of thalamic hemorrhage in terms of localization are of great interest in many studies. To better understand the relationship between the localization of thalamic hemorrhage and clinical features, we evaluated the characteristics of patients with four different topographic types of thalamic hemorrhage.

Methods
We prospectively studied 100 patients with thalamic hemorrhage who were admitted consecutively to our primary care unit. We divided them into two groups according to large (>2 cm in diameter and/or >4 mL in volume) and small thalamic hemorrhage. Four topographic subgroups (large and small) were compared to identify clinical syndromes associated with distinct lesion locations.

Results
All patients with posterolateral thalamic hemorrhage had severe sensorimotor deficit. Neuropsychological disturbances in patients with posterolateral thalamic hemorrhage were prominent, with primarily transcortical aphasia in those with left-sided lesions and hemineglect and anosognosia in those with right-sided lesions. Several variants of vertical gaze dysfunction, skew ocular deviation, gaze preference toward the site of the lesion, and miotic pupils were frequent in posterolateral thalamic hemorrhage, particularly in the large type. Patients with small and large anterolateral thalamic hemorrhage were characterized by severe motor and sensory deficits; language and oculomotor disturbances were also observed, although less frequently than in posterolateral hemorrhage. Sensorimotor deficits were observed in patients with medial thalamic hemorrhage (moderate in small hemorrhages and severe in large hemorrhages because of involvement of the adjacent internal capsule). Language disturbances in patients with left-sided lesions and neglect in patients with right-sided lesions were seen only in large medial thalamic hemorrhage. Dorsal thalamic hemorrhage was rare and characterized by mild and transient sensorimotor disturbances. Among patients with dorsal thalamic hemorrhages, only those with large lesions had oculomotor and neuropsychological disturbances.

Conclusions
We concluded that despite clinical similarity among the four types of thalamic hemorrhage, there was some discrepancy in the clinical features of small and large thalamic hemorrhages. The most important predictors of death were initial consciousness, nuchal rigidity, maximum size, volume and ventricular extension of hemorrhage, and occurrence of hydrocephalus.
Psychosocial and Health Status in Stroke Survivors After 14 Years
Authors: Tuomilehto Jaakko , Nuottimäki Tarja , Salmi Kalervo , Aho Kari , Kotila Mervi , Sarti Cinzia , Rastenytè Daiva
Published: June 2011

Background and Purpose
Most studies of long-term survival and assessment of health status in survivors of stroke are hospital based and are often based only on a relatively short follow-up. This study was aimed at evaluating survival of acute stroke after 14 years. We also assessed psychosocial and health status among the long-term stroke survivors.

Methods
This study is a follow-up of the Finnish part of the collaborative World Health Organization Stroke Study that took place during 1972 through 1974. All survivors were interviewed by telephone after being sent a structured questionnaire approximately 14 years after the initial stroke attack. Information on clinical history, socioeconomic situation, self-reported functional capacity, psychosomatic status, perceived mental status, and perceived health was collected.

Results
Of the 1241 persons who had been entered in the stroke register from 1972 through 1974, 241 (19.4%) were still alive after 14 years. Participation rate in the telephone interview was 83.4%. Over 80% of all stroke survivors lived at home or with relatives at the time of interview. Functional capacity was good in about two thirds of the stroke survivors. Only 10% to 15% of all respondents felt depressed. About half of both men and women aged 64 years or younger perceived their health as good, while only 25% of men aged 65 years or over did.

Conclusions
Most stroke survivors did not need institutionalized care in the long term. Although a large proportion of them suffered from various somatic diseases, their functional capacity was found to be good.
Incidence and Frequency of Cerebral Embolic Signals in Patients With a Similar Bileaflet Mechanical Heart Valve
Authors: Brækken Sigrun K. , Russell David , Brucher Rainer , Svennevig Jan
Published: June 2011

Background and Purpose
The aim of this study was to determine the incidence and frequency of cerebral embolic signals in a patient population with the same mechanical heart valve using transcranial Doppler examination. Furthermore, it aimed to identify patient and valve characteristics that correlated with the occurrence of these signals.

Methods
Ninety-two patients with Carbomedics valves and 15 healthy control subjects took part in the study. Thirty-six patients were examined before and immediately after valve implantation (group 1), 34 patients 1 year after surgery (group 2), and 22 patients 5 years after surgery (group 3). Cerebral embolic signals were detected using transcranial Doppler monitoring of the right middle cerebral artery.

Results
Asymptomatic cerebral embolic signals were detected in 87% of the total 92 patients, in 77.8% of group 1 patients, in 91.2% of group 2 patients, and in 95.5% of group 3 patients. No cerebral embolic signals were detected in group 1 patients before surgery or in control subjects. The incidence (
P
=.04) and frequency (
P
=.002) of cerebral embolic signals increased significantly with longer duration of valve implantation. A significant positive correlation was also found between frequency of cerebral embolic signals and valve size (
r
=.4326,
P
=.00001). Median frequency of embolic signals in patients with a history suggestive of cerebrovascular events (n=14) was 60 signals per hour compared with 11 signals per hour in those with no such history (n=42;
P
=.04).

Conclusions
The incidence and frequency of cerebral embolic signals increased with the duration of valve implantation. The frequency of these signals also was dependent on valve size. Patients who had experienced cerebrovascular symptoms had a higher frequency of cerebral embolic signals compared with those with no such signals. These results should be interpreted with caution but suggest that this method could be of help in assessing the risk of stroke in prosthetic heart valve patients and that prospective clinical studies should now be carried out.
Detection of Carotid Stenosis
Authors: Chang Yao-Jen , Golby Alexandra J. , Albers Gregory W.
Published: June 2011

Background and Purpose
Results from large multicenter studies have shown that carotid endarterectomy, performed with low perioperative morbidity and mortality, is beneficial for patients with symptomatic carotid stenosis ≥70% as calculated according to strict angiographic criteria. To apply these results in clinical practice, individual institutions should determine whether locally implemented duplex ultrasonography adequately identifies patients with ≥70% stenosis and whether the degree of stenosis reported by local angiographers correlates with strict angiographic measurements.

Methods
We compared estimates of carotid stenosis obtained by duplex ultrasonography and the radiologists’ reports from conventional cerebral angiography with each other and with results obtained using North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria.

Results
One hundred seventy-one vessels were available for review. In 155 (91%) of the cases, the reports from the ultrasound and angiogram were in agreement with regard to whether the stenosis was ≥70% or <70%. In 11 of the 16 cases where there was a disparity between the studies, the ultrasound was in closer agreement with measurements obtained using NASCET criteria. Nine of the angiography reports overestimated the degree of stenosis compared with NASCET measurements; twice angiography underestimated the stenosis. Twice the ultrasound underestimated the stenosis, and three times it overestimated the stenosis.

Conclusions
Duplex ultrasonography was highly sensitive for detecting significant carotid stenosis at our institution; however, angiography reports often graded the degree of stenosis to be more severe than measurements obtained using NASCET criteria. Institutions that evaluate patients for carotid endarterectomy should investigate the correlation between their ultrasound and angiographic studies so that the results of carotid endarterectomy trials can be accurately applied.
Inadequacy of Clinical Scoring Systems to Differentiate Stroke Subtypes in Population-Based Studies
Authors: Hawkins Glen C. , Bonita Ruth , Broad Joanna B. , Anderson Neil E.
Published: June 2011

Background and Purpose
We undertook to examine the usefulness for epidemiological studies of two well-known validated clinical scoring methods, the Guys’ Hospital Stroke score and the Siriraj Hospital Stroke score, to classify strokes into the two main types, hemorrhagic and ischemic, in epidemiological studies.

Methods
Patients from a population-based stroke register who received either a CT scan or an autopsy were retrospectively scored using the two clinical scoring methods. The scores were then compared with the CT scan and autopsy results to determine the sensitivity, specificity, and positive predictive value for intracranial hemorrhage (primary intracerebral and subarachnoid hemorrhage) and ischemic stroke.

Results
Over a 12-month period, 554 patients from a population-based study underwent CT scanning. Films or autopsy reports were available for 521 patients, and of these, sufficient clinical information to calculate the Guys’ Hospital Stroke score and the Siriraj Hospital Stroke score was available for 464 and 475 patients, respectively. For the Guys’ Hospital Stroke score, the sensitivity and specificity for intracranial hemorrhage were 31% and 95%, respectively; the positive predictive value was 73%. The sensitivity and specificity for ischemic stroke were 78% and 70%, respectively, and the positive predictive value was 86%. For the Siriraj Hospital Stroke score, the sensitivity and the specificity for intracranial hemorrhage were 48% and 85%, respectively; the positive predictive value was 59%. The sensitivity and specificity for ischemic stroke were 61% and 74%, respectively, and the positive predictive value was 84%.

Conclusions
This validation study suggests that both clinical scores lack sufficient validity to be used in epidemiological studies for classification of stroke types and should probably not be used in the randomization of patients into treatment trials using thrombolytic or antithrombotic drugs in the absence of diagnostic information based on neuroimaging techniques.
Platelet Activation Is Not Involved in Acceleration of the Coagulation System in Acute Cardioembolic Stroke With Nonvalvular Atrial Fibrillation
Authors: Nagao Takehiko , Hamamoto Makoto , Kanda Akemi , Tsuganesawa Toshikazu , Ueda Masayuki , Kobayashi Katsushi , Miyazaki Tokuzou , Terashi Akiro
Published: June 2011

Background and Purpose
It is generally accepted that the coagulation system is activated in ischemic stroke and that platelet activation is involved in the pathogenesis of this disease. However, little is known about how and to what extent platelet activity participates in coagulation system enhancement. We evaluated the hemostatic condition, especially with regard to platelet function and the coagulation system, within 3 days of onset of acute stroke. The study participants were limited to elderly patients with cardioembolic stroke due to nonvalvular atrial fibrillation.

Methods
Seventeen elderly patients with acute cardioembolic stroke due to nonvalvular atrial fibrillation were investigated. Within 3 days of stroke onset, β-thromboglobulin (BTG), platelet factor 4 (PF4), thrombin-antithrombin III complex (TAT), and
d-
dimer from arterial blood were carefully evaluated in these patients. Blood samples from 19 healthy age- and sex-matched control subjects were also examined.

Results
The two studied markers of platelet activity did not change in the patients or the control subjects, and the between-group differences between the stroke and control groups were not statistically significant (BTG, 43.8 versus 31.9 ng/mL; PF4, 9.06 versus 5.78 ng/mL; respectively). In contrast, the two studied coagulation-system indicators were markedly elevated in the patients compared with the control subjects (TAT, 13.8 versus 3.5 ng/mL,
P
<.01;
d-
dimer, 366.3 versus 147.2 ng/mL,
P
<.01; respectively).

Conclusions
Platelet function was not enhanced in the acute stage of cardioembolic stroke with nonvalvular atrial fibrillation. This result indicates that enhancement of the coagulation system in cardioembolic stroke is not the result of platelet hyperfunction, ie, “platelet-fibrin” thrombi, but rather of “stasis-related” thrombi formation.
Effects of Intermittent Reperfusion on Brain pHi, rCBF, and NADH During Rabbit Focal Cerebral Ischemia
Authors: Regli Luca , Anderson Robert E. , Meyer Fredric B.
Published: June 2011

Background and Purpose
The use of intermittent reperfusion versus straight occlusion during neurovascular procedures is controversial. This experiment studied the effects of intermittent reperfusion and single occlusion on intracellular brain pH (pH
i
), regional cerebral or cortical blood flow, and nicotinamide adenine dinucleotide (NADH) fluorescence during temporary focal ischemia.

Methods
Twenty fasted rabbits under 1.0% halothane anesthesia were divided into four groups: (1) nonischemic controls, (2) 60 minutes of uninterrupted focal ischemia, (3) 2×30-minute periods of focal ischemia separated by a 5-minute reperfusion, and (4) 4×15-minute periods of focal ischemia separated by three 5-minute reperfusion periods. Focal ischemia was produced by occlusion of both the middle cerebral and ipsilateral anterior cerebral arteries. After the final occlusion, there was a 3-hour reperfusion period in all groups. Regional cerebral and cortical blood flow, brain pH
i
, and NADH fluorescence were measured with in vivo panoramic fluorescence imaging.

Results
During occlusion, regional cerebral and cortical blood flows and NADH fluorescence values were not different among the groups. Brain pH
i
was significantly lower in the 4×15-minute group compared with the 1×60-minute group (6.57±0.02 versus 6.73±0.06;
P
<.03) but not significant when compared with the 2×30-minute group. During the short reperfusion periods, all parameters returned to normal except for NADH fluorescence levels, which remained elevated. During the postischemic final reperfusion period, there was a mild brain alkalosis of approximately 7.1 in all groups. There were no significant differences in NADH fluorescence among groups during the final reperfusion. Regional cerebral and cortical blood flow returned to near normal values in all groups.

Conclusions
This study demonstrates that intermittent reperfusion during temporary focal ischemia has different effects on the intracytoplasmic and the intramitochondrial compartments: worsening of brain cytoplasmic pH
i
but no significant differences in the oxidation/reduction level of mitochondrial NADH.
Vertical Gaze Palsies From Medial Thalamic Infarctions Without Midbrain Involvement
Authors: Clark Joni M. , Albers Gregory W.
Published: June 2011

Background
Although the supranuclear pathways for vertical gaze control are not well defined, lesions of the mesencephalic reticular formation including the nucleus of Darkschewitsch, the rostral interstitial medial longitudinal fasciculus, the interstitial nucleus of Cajal, and the posterior commissure are known to produce vertical gaze palsies. MRI studies have not previously reported isolated thalamic lesions as the cause of vertical gaze palsies.

Case Descriptions
Three patients with acute paralysis of vertical gaze were imaged with MRI. Sagittal T
1
and axial T
1
, T
2
, and proton-weighted images were obtained. All three patients had repeated scans performed from 3 days to 6 weeks after the original study. Two patients exhibited unilateral right thalamic infarcts (polar and paramedial territory), and one patient had a bilateral paramedian thalamic infarction. There was no evidence of midbrain involvement on any of the images.

Conclusions
Vertical gaze palsies are known to be produced by lesions of the rostral interstitial medial longitudinal fasciculus. This MRI study reveals thalamic infarctions without associated midbrain infarctions in three patients with vertical gaze palsies. This may be explained by interruption of supranuclear inputs.
Clinical and Biochemical Analysis in Infection-Associated Stroke
Authors: Grau Armin J. , Buggle Florian , Steichen-Wiehn Christianne , Heindl Silke , Banerjee Tomas , Seitz Rainer , Winter Ralph , Forsting Michael , Werle Egon , Bode Christoph , Nawroth Peter-Paul , Becher Heiko , Hacke Werner
Published: June 2011

Background and Purpose
Currently, recent infection (primarily bacterial infection) is discussed as a risk factor for cerebrovascular ischemia. The aim of this study was to investigate whether the association of ischemic stroke with recent infection is restricted to stroke subtypes and whether recent infection influences the severity of the postischemic deficit; we also aimed to define biochemical pathways linking infection and ischemic stroke.

Methods
Analyzing the data of a prospective case-control study, we classified the etiology of cerebrovascular ischemia on the basis of clinical, neuroradiological, sonographical, cardiological, and biochemical data in 159 patients without and in 38 patients with infection within 1 week before ischemia. We assessed the severity of neurological deficits using the Scandinavian Stroke Scale.

Results
In patients with recent infection compared with patients without infection, the neurological deficit on admission was more severe (median of scores, 41 versus 30.5;
P
<.005), cortical infarcts in the middle cerebral artery territory were more frequent (60% versus 26%;
P
<.001), the prevalence of extracranial artery stenoses was lower (9% versus 26%;
P
<.05), and definite or presumed cardioembolic stroke was more frequent (34% versus 19%;
P
<.05), as was stroke from cervical artery dissection (8% versus 1.3%;
P
=.05). Serum levels of C-reactive protein were higher in patients with (20.7±26.8 mg/L) than in those without infection (9.2±23.7 mg/L;
P
<.01).

Conclusions
Recent infection may be associated with a more severe postischemic deficit and with an increased risk of stroke from cardioembolic origin and from cervical arterial dissection.
Basic Fibroblast Growth Factor May Repair Experimental Cerebral Aneurysms in Rats
Authors: Futami Kazuya , Yamashita Junkoh , Tachibana Osamu , Kida Shinya , Higashi Sotaro , Ikeda Kiyonobu , Yamashima Tetumori
Published: June 2011

Background and Purpose
To determine whether basic fibroblast growth factor (FGF) can induce proliferative response of endothelial cells and/or smooth muscle cells in aneurysmal lesions, we investigated the effect of the intravenous administration of basic FGF on experimental cerebral aneurysms.

Methods
Cerebral aneurysms were induced in rats by ligation of the unilateral common carotid artery, producing hypertension. Three months later, basic FGF was intravenously injected in two groups of randomly divided rats on days 1, 3, and 5 at two different doses (low dose: 2 μg/100 g body wt per day; high dose: 5 μg/100 g body wt per day). In a control group, normal saline was similarly injected. The junctions of the anterior cerebral artery (ACA) and the olfactory artery (OA) were examined with a light microscope. Aneurysmal changes were defined as the lesions with discontinuity of the internal elastic lamina in more than half of the outward dilated wall. Depending on whether the smooth muscle cell layer was present in the whole wall, the lesions were divided into two stages: early aneurysmal lesion (whole area) and saccular aneurysm (not totally preserved).

Results
The control and the low-dose groups presented no obvious intimal thickening in the intact ACA-OA junctions of both nonligated and ligated sides as well as in the aneurysmal changes. In contrast, in the high-dose group, various degrees of intimal thickening in the wall were detected in 7 of 15 early aneurysmal lesions (
P
=.019, Fisher’s exact test). Immunohistochemistry showed the proliferated cells to be smooth muscle cells.

Conclusions
These results demonstrate that exogenous basic FGF induces the proliferative response of smooth muscle cells in aneurysmal lesions in rats.
Hypertensive Cerebrovascular Disease and the Renin-Angiotensin System
Authors: Rossi GianPaolo , Rossi Alberto , Sacchetto Alfredo , Pavan Edoardo , Pessina Achille C.
Published: June 2011

Background
Arterial hypertension is the leading cause of cardiovascular disease and is associated with an increased risk of stroke and heart attack. These complications have been largely attributed to the remodeling of the arterial wall, including accelerated atherosclerosis occurring in hypertensive patients. Although the risk of haemorrhagic stroke seems to be directly related to the level of blood pressure elevation, no such tight relationship has been found between blood pressure levels and atherosclerosis. This observation has led to the concept that a number of genetic, humoral, and cellular factors may be involved in atherogenesis in hypertensive patients.

Summary of Review
The experimental and clinical evidence concerning the role of the renin-angiotensin system in cardiovascular remodeling and atherogenesis of the cerebrovascular bed as well as the data supporting an association between angiotensin II and thrombotic stroke are examined.

Conclusions
The contribution of the renin-angiotensin system to the pathogenesis of accelerated carotid artery atherosclerosis and particularly of cerebrovascular disease remains to be definitively proven. However, the bulk of experimental and clinical data are consistent with the hypothesis that the renin-angiotensin system may play a detrimental role.
Role of Potassium Channels in Cerebral Blood Vessels
Authors: Kitazono Takanari , Faraci Frank M. , Taguchi Hisao , Heistad Donald D.
Published: June 2011

Background
Hyperpolarization of vascular muscle in response to activation of potassium channels is a major mechanism of vasodilatation. In cerebral blood vessels, four different potassium channels have been described: ATP-sensitive potassium channels, calcium-activated potassium channels, delayed rectifier potassium channels, and inward rectifier potassium channels.

Summary of Review
Activation of ATP-sensitive and calcium-activated potassium channels appears to play a major role in relaxation of cerebral arteries and arterioles in response to diverse stimuli, including receptor-mediated agonists, intracellular second messengers, and hypoxia. Both calcium-activated and delayed rectifier potassium channels may contribute to a negative feedback system that regulates tone in large cerebral arteries. The influence of ATP-sensitive and calcium-activated potassium channels is altered in disease states such as hypertension, diabetes, and atherosclerosis.

Conclusions
Activation of potassium channels is a major mechanism of cerebral vasodilatation. Alteration of activity of potassium channels and impairment of vasodilatation may contribute to the development or maintenance of cerebral ischemia or vasospasm.
Trauma-Induced Neurotoxicity in Rat Hippocampal Neurons
Authors: Yoon Kong-Woo , Mitchell Horace L. , Broder Lawrence D. , Brooker Robert W. , Delisle Robert K.
Published: June 2011

Background and Purpose
We have previously shown that traumatic injury of hippocampal cells triggers release of a soluble neurotoxin that can be transferred to an uninjured culture. The mechanism of this trauma-induced neurotoxicity is independent of glutamate receptor activation. We extended this observation to study the mechanism of this neurotoxicity.

Methods
Dissociated rat hippocampal neurons were traumatized by disrupting the culture by scratching the plate. The toxicity expressed by the injured culture was studied by transferring the medium to an uninjured culture and assessing the death rate by trypan blue exclusion.

Results
This neurotoxin is stable in the medium at room temperature for several hours and withstands boiling. The molecular weight is between 100 and 500. The release and the effect of this toxin seem to be independent of glutamate receptor activation. The toxicity is unaffected by removal of extracellular calcium. However, dantrolene dose-dependently blocked the toxicity in the recipient culture, suggesting that the release of intracellular stores of calcium is involved in the toxic effect. This release of calcium is likely to be followed by an activation of nitric oxide synthase because competitive nitric oxide synthase inhibitors attenuated this toxicity. Consistent with this result, cholecystokinin octapeptide significantly reduced cell death when combined with this toxic medium.

Conclusions
Traumatic injury of dissociated cells can propagate neurotoxicity in uninjured cells by a soluble toxin released into the extracellular space. This toxin causes a rise in cytosolic calcium that activates nitric oxide synthase that can be blocked by cholecystokinin.
Ischemia Reduces CGRP-Induced Cerebral Vascular Dilation in Piglets
Authors: Louis Thomas M. , Meng Wei , Bari Ferenc , Errico Robert A. , Busija David W.
Published: June 2011

Background and Purpose
Effects of anoxic stress on cerebrovascular responses to calcitonin gene–related peptide (CGRP) have not been examined previously. We determined the effects of total global ischemia on cerebral arteriolar responses to CGRP in newborn pigs.

Methods
Piglets were anesthetized and ventilated with a respirator. Pial arteriolar diameter was determined using a closed cranial window and intravital microscopy. Baseline arteriolar diameters ranged from 80 to 100 μm. Arteriolar responses to 10
−9
and 10
−8
mmol/L CGRP applied topically were determined before and 1, 2, and 4 hours after a 10-minute period of total global ischemia. Ischemia was caused by increasing intracranial pressure.

Results
Before ischemia, CGRP dilated arterioles by 14±2% (n=6) and 24±3% (n=7) at 10
−9
and 10
−8
mmol/L, respectively. However, after ischemia, arteriolar responses to 10
−9
mmol/L CGRP were reduced at 1 hour to 4±1%, at 2 hours to 3±2%, and at 4 hours to 5±4% (
P
<.05 for all comparisons). Similarly, arteriolar responses to 10
−8
mmol/L CGRP were reduced to 5±2% at 1 hour, 5±2% at 2 hours, and 10±6% at 4 hours (
P
<.05 for all comparisons). In time control animals, arteriolar responses to CGRP did not change over time. In other animals, we examined effects of pretreatment with indomethacin (5 mg/kg IV) on ischemia-induced decreases in arteriolar responses to CGRP. Indomethacin administration did not preserve arteriolar dilation to CGRP at 1 hour after ischemia, but responses were normal at 2 hours.

Conclusions
Total global ischemia leads to prolonged attenuated dilator responses of cerebral arterioles to CGRP. In addition, indomethacin treatment alters effects of ischemia on CGRP-induced dilation.
Influence of the Intra-Aortic Balloon Pump on the Transcranial Doppler Flow Pattern in a Brain-dead Patient
Authors: van der Naalt J. , Baker A.J.
Published: June 2011

Background
Confirmation of clinical brain death with transcranial Doppler (TCD) has been described. With the introduction of mechanical assist devices, it is important to know how these devices influence TCD measurements.

Case Description
A patient who fulfilled the clinical criteria for brain death after cardiac arrest is described. An intra-aortic balloon pump (IABP) was necessary to maintain hemodynamic stability. A TCD examination was performed as an adjunct to the clinical diagnosis of brain death. A pattern of reversal of blood velocity typical of brain death was observed. With the IABP functioning, an increase of mean forward flow velocity without appreciable increase in the net flow velocities was seen. The results of the TCD measurements with the IABP functioning are not in concordance with values reported in the literature that confirm the clinical diagnosis of brain death.

Conclusions
Application of TCD in a patient with an IABP could lead to false interpretation of results if the TCD mean velocities are not registered with the IABP on standby or if the net flow velocities are not calculated.
Cerebral Oximetry in Patients Undergoing Carotid Endarterectomy Under Regional Anesthesia
Authors: Samra Satwant K. , Dorje Pema , Zelenock Gerald B. , Stanley James C.
Published: June 2011

Background and Purpose
Near-infrared spectroscopy is a technique that can potentially monitor changes in cerebral oxygenation. There are at present limited clinical data regarding the value of this technology in relating neurological outcome to cerebrovascular hemoglobin oxygen saturation (Sc
o
2
). This investigation reports changes in Sc
o
2
due to carotid cross-clamping during carotid endarterectomy in awake patients.

Methods
Sc
o
2
was monitored in 38 adult patients undergoing 41 carotid endarterectomies under regional anesthesia. Ipsilateral and contralateral hemispheres were monitored simultaneously during 36 operations, with ipsilateral monitoring alone in the remaining 5 operations.

Results
No significant difference was detected between ipsilateral and contralateral Sc
o
2
during preclamp or postclamp periods. Carotid cross-clamping caused a statistically significant (
P
<.01) decrease in the ipsilateral Sc
o
2
, which decreased from 71.8±6.91% to 65.8±8.2%, while the contralateral Sc
o
2
remained stable at 70.5±7.5% and 70.3±7.9%. The change in ipsilateral Sc
o
2
ranged from +2.6% to −28.6% of the preclamp value. The difference between ipsilateral and contralateral Sc
o
2
during cross-clamping was statistically significant (
P
<.001). The duration of cross-clamping was 39±11 minutes (range, 18 to 89 minutes). The decrease in ipsilateral Sc
o
2
was highly variable from patient to patient and did not correlate with the duration of cross-clamping.

Conclusions
These results suggest that carotid artery occlusion causes a statistically significant but variable decrease in Sc
o
2
in the majority of patients. Data in this investigation provide a range of Sc
o
2
values that was not associated with a clinically detectable neurological dysfunction.
Predictors of Stroke in Middle-Aged Patients With Non–Insulin-Dependent Diabetes
Authors: Lehto Seppo , Rönnemaa Tapani , Pyörälä Kalevi , Laakso Markku
Published: June 2011

Background and Purpose
The risk of stroke is known to be markedly elevated in patients with non–insulin-dependent diabetes mellitus (NIDDM), but the information on risk factors predicting stroke events in middle-aged NIDDM patients is limited. Therefore, we evaluated the significance of different cardiovascular risk factors with respect to the incidence of stroke in middle-aged NIDDM patients.

Methods
Levels of cardiovascular risk factors were determined at baseline in 1059 NIDDM patients (581 men, 478 women) and 1373 nondiabetic control subjects (638 men, 735 women), aged from 45 to 64 years, in eastern and western Finland. These patients were followed up for 7 years with respect to stroke events.

Results
Altogether, 34 NIDDM patients (13 men, 21 women) and 5 nondiabetic subjects (4 men, 1 woman) died from stroke, and 125 NIDDM patients (61 men, 64 women) and 30 (18 men, 12 women) nondiabetic subjects had a fatal or nonfatal stroke. The risk of stroke in NIDDM men was about threefold and in NIDDM women fivefold higher than that in corresponding nondiabetic subjects. Previous history of stroke increased the risk of a new stroke event by threefold. Patients with hyperglycemia (plasma glucose >13.4 mmol/L) and high hemoglobin A
1
(>10.7%) had about a twofold higher risk of stroke than patients with better glycemic control. Low levels of high-density lipoprotein cholesterol (<0.90 mmol/L), high levels of total triglyceride (>2.30 mmol/L), and the presence of hypertension were associated with a twofold increase in the risk of stroke mortality or morbidity.

Conclusions
Our prospective population-based study gives evidence that previous history of stroke, hypertension, hyperglycemia, and dyslipidemia are strong predictors of stroke in middle-aged patients with NIDDM.
The Tel Aviv Stroke Registry
Authors: Bornstein Natan M. , Aronovich Boris D. , Karepov Vadim G. , Gur Alex Y. , Treves Therese A. , Oved Michal , Korczyn Amos D.
Published: June 2011

Background and Purpose
We undertook to estimate the frequency of various risk factors and the type and severity of stroke in different ethnic groups documented in a large hospital-based stroke registry. Tel Aviv is a metropolis with about 400 000 inhabitants and about 600 000 daily visitors and workers. The Tel Aviv Medical Center (TAMC) is the only tertiary medical care facility to which all patients with acute stroke are referred. Israel is a country with a heterogeneous population, of which a significant proportion was born abroad. The people differ in their genetic background, as well as in their early environmental conditions, lifelong diet, and other habits. This variety has proved to be a fertile ground for the study of different neurological diseases, including stroke.

Methods
A prospective hospital-based registry using systematic computer coding of data of all consecutive stroke patients admitted to the TAMC has been conducted since May 1988. Different aspects of the amassed data were analyzed statistically.

Results
From May 1988 until April 1994, 3600 stroke patients were admitted to the TAMC. The mean age was 73.2 years, and 58.2% were males. Cerebral infarctions were diagnosed in 80.9%, primary intracerebral hemorrhages in 8.0%, and transient ischemic attacks in 11.1%. There were 861 patients (24%) who were admitted with recurrent strokes. Past medical history of hypertension was the major risk factor (occurring in 52.2% of the patients), followed by ischemic heart disease (29.7%), diabetes mellitus (25.2%), smoking (17.0%), atrial fibrillation (14.3%), and hyperlipidemia (8.4%). Ischemic heart disease and atrial fibrillation were more frequent in patients from Europe and America (Ashkenazi group), whereas diabetes mellitus and smoking were more prominent in the other groups. The in-hospital mortality rate was 13.8% and was similar in both ethnic groups.

Conclusions
This registry allows the study of the risk factors, natural history, and clinical manifestations of stroke in different ethnic groups.
Validation of the Short Form 36 (SF-36) Health Survey Questionnaire Among Stroke Patients
Authors: Anderson Craig , Laubscher Sara , Burns Richard
Published: June 2011

Background and Purpose
Few studies have examined the utility of a new generic health status measure, the Short Form 36 health survey questionnaire (SF-36), in stroke patients. Our aim was to test the internal consistency and validity of the SF-36 in a cohort of long-term stroke survivors.

Methods
The Australian version of the SF-36 was tested in 90 consecutive 1-year stroke survivors (mean age, 72 years) identified from our hospital discharge data. The instrument was administered by personal interview. Validity was assessed by comparing patients' scores on the SF-36 with those obtained for the Barthel Index, the 28-item General Health Questionnaire, and the Adelaide Activities Profile, an instrument developed from the Frenchay Activities Index.

Results
The SF-36 was relatively quick and easy to use and had satisfactory internal consistency (Cronbach's α>0.7). For all eight SF-36 health scales, the mean scores for patients dependent in self care and with mental ill health were significantly different from patients without these disabilities, but the strength of the differences varied in a predictable manner. However, the SF-36 social functioning scale did not provide a valid measure of everyday activities relevant to many elderly patients as measured by the Adelaide Activities Profile.

Conclusions
The SF-36 avoids the “ceiling effect” of most disability scales and provides a valid measure of physical and mental health after stroke, but it does not appear to characterize well social functioning. Thus, the instrument may need to be supplemented by other measures for a comprehensive assessment of stroke outcome.
Ethical Considerations in Clinical Neuroscience
Authors: Alves Wayne A. , Macciocchi Stephen N.
Published: June 2011

Background
Ethical decision making in clinical trials has become increasingly emphasized at many levels of the review process.

Summary of Review
Ethical concepts applicable to neuroclinical trials are reviewed. The discussion is directed toward ethical concerns that investigators must consider and justify prior to institutional review board submission. Risk-benefit analysis, methodology (randomization, placebo, design), and consent (informed, deferred, waived) are reviewed and guidelines of the Office for Protection From Research Risk are described.

Conclusions
Investigators proposing neuroclinical trials face increasing ethical scrutiny by institutional review boards. Attention to ethical issues early in the trial planning process is recommended.