bluuebunny/crossref_metadata_2025 huggingface dataset:
Beagle pup germinal matrix maturation studies.
Authors: Ment L R , Stewart W B , Ardito T A , Madri J A
Published: June 2011

Intraventricular hemorrhage, or hemorrhage into the germinal matrix tissues of the developing brain, remains a common problem of preterm infants. The "risk period" for this insult is the first 3-4 postnatal days. We hypothesized that this risk period for hemorrhage is related to rapid perinatal maturation of the germinal matrix vasculature and employed the newborn beagle pup model for the study of this maturation. Newborn beagle pups (n = 30) were anesthetized and systemically perfused with buffered formalin; the brains were removed and prepared for immunohistochemical study. Sections stained with Bandeiraea lectin demonstrated that there was no difference in germinal matrix vessel density between postnatal days 1 and 4. Germinal matrix sections were also stained for antibodies to alpha-smooth muscle actin, collagen IV, collagen V, desmin, factor VIII-related antigen, fibronectin, glial fibrillary acidic protein, laminin, transferrin, and vimentin. Vasculature staining by alpha-smooth muscle actin was not noted until postnatal day 10, and differential staining was detected for antibodies to laminin and collagen V. Quantification of staining intensity by confocal microscopy demonstrated a significant increase in both extracellular matrix components at postnatal day 4 compared with day 1 (p less than 0.05 for both). These basement membrane proteins may add sufficient structural integrity to germinal matrix vessels to prevent capillary rupture and thus intraventricular hemorrhage.
Selective attenuation by perivascular blood of prostanoid-dependent cerebrovascular dilation in piglets.
Authors: Busija D W , Leffler C W
Published: June 2011

Cerebral hemorrhagic insults are common in neonates. However, the consequences of intracranial blood on cerebral hemodynamics are poorly understood. We examined the effects of perivascular blood on cerebrovascular dilator responses in 29 piglets. Fresh, autologous blood (n = 15) or cerebrospinal fluid (n = 14) was placed under the dura mater over the parietal cortex, and the piglets were allowed to recover from anesthesia. One to four days later, a closed cranial window was placed over the parietal cortex and pial arteriolar responses to arterial hypercapnia (PaCO2 greater than 55 mm Hg), hemorrhagic hypotension (mean arterial blood pressure less than 35 mm Hg), or topical application of 10(-6) and 10(-4) M isoproterenol were determined. Pial arterioles in the cerebrospinal fluid group dilated 27 +/- 4% (mean +/- SEM) (n = 11) in response to hypercapnia, 26 +/- 5% (n = 9) in response to hypotension, and 26 +/- 3% in response to 10(-6) M and 40 +/- 4% in response to 10(-4) M isoproterenol (n = 11). In the group in which blood was placed on the parietal cortex, pial arterioles did not dilate significantly in response to hypercapnia (8 +/- 3%, n = 11) or hypotension (2 +/- 5%, n = 13) but dilated normally in response to isoproterenol (25 +/- 5% in response to 10(-6) M and 36 +/- 7% in response to 10(-4) M, n = 13). We conclude that prolonged contact of pial arterioles with extravascular blood selectively attenuates cerebrovascular dilation in piglets.
Superoxide dismutase decreases mortality, blood pressure, and cerebral blood flow responses induced by acute hypertension in rats.
Authors: Zhang X M , Ellis E F
Published: June 2011

Oxygen radicals are known to be produced by the cerebral vasculature during acute, pressor-induced hypertension and are also known to inactivate endothelium-derived relaxing factor. The objective of our present study was to determine if the oxygen radical scavenger superoxide dismutase (24,000 units/kg plus 1,600 units/kg/min) alters the pressor, cerebral blood flow, and mortality responses to systemic norepinephrine in rats. Increasing doses (0.01-30 micrograms/kg i.v.) of norepinephrine were given by bolus injection to eight rats, and changes in the cortical microcirculatory blood flow were measured by laser-Doppler flowmetry. Superoxide dismutase shifted the norepinephrine-blood pressure and -cerebral blood flow dose-response curves moderately, but significantly, to the right such that it took more norepinephrine to reach a given blood pressure. However, superoxide dismutase had no effect on the autoregulation of cerebral blood flow. Additionally, whereas five (63%) of the eight control rats died after the 10 micrograms/kg norepinephrine dose, all eight rats treated with superoxide dismutase survived this dose. The mechanism by which superoxide dismutase reduced mortality is uncertain. The blood pressure and cerebral blood flow results suggest that superoxide dismutase prevents oxygen radicals from destroying endothelium-derived relaxing factors, which reduce the pressor effects of norepinephrine.
Description of a closed window technique for in vivo study of the feline basilar artery.
Authors: Bouma G J , Levasseur J E , Muizelaar J P , Wiatt R G , Kontos H A
Published: June 2011

Recent interest in the regulatory functions of large cerebral arteries has led to many studies addressing the specific reactivity of these vessels. Current data originate mainly from in vitro experiments, as in vivo studies of larger intracranial cerebral arteries have been cumbersome so far due to the lack of a suitable animal model. We provide a detailed technical description of a closed transclival window method for in vivo study of the basilar artery in cats. We present our experience with this preparation in 29 animals, which shows that the technique is feasible and allows repeated, accurate, and reproducible measurements of the basilar artery, although possible depressive effects of the anesthesia on vascular reactivity have to be taken into account. With hyperventilation, the basilar artery constricted by 12.2 +/- 7.6% of the baseline diameter. The cerebral blood flow response to hypocapnia with this preparation was 2.0 +/- 0.4%/torr PaCO2. An exudative clouding of the window occurred in some cats but had no apparent effect on vascular reactivity. We also discuss possible pitfalls in the surgical preparation.
Amphetamine promotes recovery from sensory-motor integration deficit after thrombotic infarction of the primary somatosensory rat cortex.
Authors: Hurwitz B E , Dietrich W D , McCabe P M , Alonso O , Watson B D , Ginsberg M D , Schneiderman N
Published: June 2011

The present studies were undertaken to examine 1) whether d-amphetamine sulfate administered to rats well after thrombotic infarction of the vibrissal cortical barrel-field within the primary somatosensory cortex affected the rate and completeness of behavioral recovery and 2) whether a dose-response relation exists between d-amphetamine sulfate dose and recovery of function. In a learning task requiring sensory-motor integration, 41 rats were trained to perform a motor response in a T-maze consequent to the detection of a vibrissal deflection cue. Once training was complete, unilateral (n = 29) or sham (n = 12) infarction was produced by a noninvasive photochemical technique. After infarction, T-maze performance was assessed repeatedly in rats receiving 2 (n = 10) or 4 (n = 10) mg/kg d-amphetamine sulfate or saline (n = 9) 24 hours prior to testing on days 4, 6, 9, and 11. The sham-operated control rats received d-amphetamine sulfate (n = 7) or no injections (n = 5). All three infarcted groups displayed a reliable and sustained behavioral deficit in performance that was not present in the sham-operated control animals. Although the performance of each infarcted group improved over the testing sessions after the first injection, the amphetamine-treated groups improved at a faster rate than the saline-injected group. The results further demonstrated a dose-response effect, with the 4 mg/kg amphetamine group recovering to within preinfarction levels 6-8 days earlier than the 2 mg/kg amphetamine and saline-injected groups. Moreover, both amphetamine-treated groups recovered more completely than the saline-injected group. Quantification of the chronic infarct area revealed no differences among the amphetamine-treated and saline-injected groups. These data provide further evidence of the facilitatory effect of d-amphetamine sulfate on recovery from brain injury and extend this effect to the enhancement of recovery subsequent to thrombotic infarction of the primary somatosensory cortex.
Fourier analysis of the cerebrovascular system.
Authors: Njemanze P C , Beck O J , Gomez C R , Horenstein S
Published: June 2011

We performed Fourier analysis of the middle cerebral artery blood flow velocity waveform envelope in 14 normal subjects (group A) and 15 patients, of whom five had arteriovenous malformations (group B), five had cerebral vasospasm (group C), and five had arterial hypertension (group D). Measurements were obtained under conditions of normocapnia, hypercapnia, and hypocapnia. The Fourier coefficients measured in the first five harmonics of the Doppler waveforms of group A were used as the reference baseline and were compared with the coefficients found in the other three groups. Group B showed significantly lower Fourier coefficients, while groups C and D showed higher coefficients (p less than 0.05). The elevation of the Fourier coefficients occurred in an alternating pattern in group C and a decremental pattern in group D. This distinction was attributed to possible differences in the underlying pathophysiological processes. The degree of vascular distensibility of the cerebral arterioles, inferred from the shape of the Fourier analysis curves, was compared in all four groups. Vascular distensibility was characterized as abnormal in arteriovenous malformations, vasospasm, and arterial hypertension. Fourier coefficients may be better indicators of cerebrovascular abnormalities than mean blood flow velocity in hypertension and pulsatility index in arteriovenous malformations, vasospasm, and hypertension.
Headache in transient or permanent cerebral ischemia. Dutch TIA Study Group.
Authors: Koudstaal P J , van Gijn J , Kappelle L J
Published: June 2011

We studied headache features in 3,126 patients with acute cerebral or retinal ischemia. Headache occurred in 18% of these patients (in 16% of all patients with transient ischemic attacks, in 18% of patients with reversible ischemic neurologic deficits, and in 19% of patients with minor strokes) and was mostly continuous in all types of attacks. Headache was present in 16% of patients with monocular visual symptoms. The occurrence of headache was not related to the mode of onset, mode of disappearance, or duration of the attack. Patients with headache more often were known to have heart disease. Headache was less frequent in patients with small deep infarcts, who were more often hypertensive, and in patients with infarcts in the anterior circulation; headache was more frequent in patients with cortical infarcts and in patients with infarcts in the posterior circulation. Patients with a relevant small deep infarct on computed tomographic scan and accompanying headache relatively often reported symptoms compatible with cortical ischemia, such as language disorders or a visual field defect. We conclude that headache is a frequent accompanying symptom in patients with acute cerebral and retinal ischemia and that the occurrence of headache is partly related to the underlying cause of the ischemic lesion.
Atrial fibrillation as a risk factor for deep venous thrombosis and pulmonary emboli in stroke patients.
Authors: Noel P , Gregoire F , Capon A , Lehert P
Published: June 2011

In 539 consecutive stroke patients admitted to a rehabilitation department, we studied the possible role of atrial fibrillation as a risk factor for deep venous thrombosis and pulmonary embolism by analyzing a series of relevant clinical data in patients with and without atrial fibrillation and in patients with and without venous thromboembolic complications. Deep venous thrombosis as well as advanced age and cardiac disease were significantly (p less than 0.001) more frequent in patients with atrial fibrillation. However, in a model of simultaneous logistic regression carried out on the presence of absence of venous thromboembolic complications, atrial fibrillation was the only significant risk factor. In view of the morbidity and mortality linked to deep venous thrombosis, our findings argue for preventive anticoagulation therapy in stroke patients suffering from atrial fibrillation and merit further study.
Measurement of regional cerebral blood flow using ultrafast computed tomography. Theoretical aspects.
Authors: Gobbel G T , Cann C E , Fike J R
Published: June 2011

Theoretical and practical limitations have prevented the measurement of regional cerebral blood flow using dynamic x-ray computed tomography. Development of the ultrafast computed tomography scanner has made it possible to overcome the practical limitations and measure changes in contrast concentration in the brain with excellent time and spatial resolution. By applying modifications of indicator dilution theory, we have derived a method to use these changes in contrast concentration determined using ultrafast computed tomography to measure the fractional vascular volume, mean transit time of blood, and blood flow within specific regions of the brain in a relatively simple and practical manner. This method could theoretically be used in the evaluation of physiological and pathophysiological alterations in cerebral blood flow.
Measurement of regional cerebral blood flow in the dog using ultrafast computed tomography. Experimental validation.
Authors: Gobbel G T , Cann C E , Iwamoto H S , Fike J R
Published: June 2011

The applicability, feasibility, reproducibility, and accuracy of the method of measuring regional cerebral blood flow using ultrafast computed tomography were evaluated in 25 dogs under varying physiological and pathophysiological conditions. Regional cerebral blood flow values were 75.6 +/- 29.4 ml/100 g/min (mean +/- standard deviation) for the hemisphere, 68.4 +/- 28.2 ml/100 g/min for the basal ganglia, 41.2 +/- 15.0 ml/100 g/min for the internal capsule, and 80.8 +/- 37.2 ml/100 g/min for the neocortex. Measurements made 10 minutes apart were significantly (p less than 0.05) correlated. Simultaneous measurements of regional cerebral blood flow by the microsphere and ultrafast computed tomography methods showed a significant (p less than 0.05) correlation for the hemisphere (r = 0.95), basal ganglia (r = 0.95), and neocortex (r = 0.94) but not for the internal capsule (r = 0.51). Microsphere and ultrafast computed tomography regional cerebral blood flow values were also in agreement in radiation-damaged brain with appreciable blood-brain barrier breakdown, and the two methods demonstrated similar responsiveness of regional cerebral blood flow to alterations in arterial carbon dioxide tension. The accuracy and sensitivity of the ultrafast computed tomography technique suggests that it affords a useful new tool for studying normal and abnormal regional cerebral blood flow.
Endothelium-dependent influence of small changes in extracellular magnesium concentration on the tone of feline middle cerebral arteries.
Authors: Szabó C , Faragó M , Dóra E , Horváth I , Kovách A G
Published: June 2011

The aim of this study was to investigate the effect of small alterations in the extracellular magnesium concentration on the tone of feline middle cerebral arteries and to examine the role of the endothelium in these responses. We measured the isometric tension of isolated arterial rings placed between two stainless steel wires in a tissue chamber containing Krebs-Henseleit solution aerated with a gas mixture containing 95% O2 and 5% CO2 at 37 degrees C. After precontraction with noradrenaline, a decrease of the extracellular magnesium concentration from 1.2 mM to 1.0 and 0.8 mM resulted in sustained relaxations, whereas elevation of the extracellular magnesium concentration from 0.8 mM to 1.2 mM caused an increase in vascular tone when the endothelium was intact. The magnesium deficiency-related dilations were absent in endothelium-denuded vessels and were inhibited by 5 x 10(-6) M oxyhemoglobin and 10(-5) M methylene blue, suggesting the involvement of an endothelium-derived relaxing factor in this vascular response. However, 5 x 10(-7) M nifedipine or 3 x 10(-5) M dichlorobenzamil did not affect the magnesium deficiency-related relaxations. Therefore, nifedipine-sensitive calcium channels or the sodium/calcium antiport system are not involved in this vascular action of magnesium. We conclude that small alterations in the extracellular magnesium concentration, possibly within the physiological range, are able to modify the basal formation and release of endothelium-derived relaxing factor and thus alter arterial smooth muscle tone in this vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)
Bilateral anterior cerebral artery infarction resulting from explosion-type injury to the head and neck.
Authors: Lipschutz J H , Pascuzzi R M , Bognanno J , Putty T
Published: June 2011

A 43-year-old woman suffered a blast-type injury to the head and neck. She subsequently developed bilateral internal carotid artery occlusion and bilateral anterior cerebral artery infarction not demonstrated by magnetic resonance imaging scan 24 hours after the explosion, but confirmed by a second scan 8 days after the explosion. In patients with blast-type injury to the head and neck who develop coma with a nonfocal neurological exam, the possibility of bilateral carotid artery occlusion and bilateral ischemic infarction should be considered.
Family history in patients with transient ischemic attacks.
Authors: Brass L M , Shaker L A
Published: June 2011

To determine the influence of family history on vascular disease, we surveyed hospital patients discharged with a diagnosis of transient ischemic attack. Of 117 respondents, 81 knew their family history for myocardial infarction and 81 knew their family history for stroke. Of 83 responding 43 reported a personal history of myocardial infarction, and of 85 responding 66 reported a personal history of stroke. As expected, there was an association between positive family and personal histories of myocardial infarction in younger (aged less than 70 years) patients (Fisher's two-tailed exact test, p = 0.014). This association was reversed for stroke (Fisher's two-tailed exact test, p = 0.017). Older (aged greater than or equal to 70 years) patients had a stronger association between positive family and personal histories of stroke; 14 (74%) of 19 older patients with a positive personal history of stroke had a positive family history of stroke. The reason for this reversal in the relation between family and personal histories of stroke compared with myocardial infarction may relate to the older age at onset of most strokes, differing stroke subtypes in older age groups, or lower rates of fatal myocardial infarction. This study suggests that familial factors may be important in some subtypes of cerebrovascular disease. Familial effects may be different in vascular diseases of the heart and brain.
Cerebral hemorrhagic risk of aspirin or heparin therapy with thrombolytic treatment in rabbits.
Authors: Clark W M , Madden K P , Lyden P D , Zivin J A
Published: June 2011

We studied the incidence of cerebral hemorrhage in an animal model of embolic stroke to determine the safety of aspirin, heparin, and tissue plasminogen activator therapies. We occluded the middle cerebral arteries of rabbits with labeled blood clots and administered either tissue plasminogen activator, heparin, aspirin, tissue plasminogen activator plus aspirin, tissue plasminogen activator plus heparin, or saline at various times after stroke. Compared to saline controls, both the aspirin-only and the tissue plasminogen activator-plus-aspirin groups had a significantly higher incidence of cerebral hemorrhage, whereas the heparin and tissue plasminogen activator combination groups did not. We conclude that aspirin antiplatelet therapy alone may increase the risk of hemorrhagic infarction, whereas heparin or tissue plasminogen activator therapy appears to be relatively safe.
Pretreatment with U74006F improves neurologic outcome following complete cerebral ischemia in dogs.
Authors: Perkins W J , Milde L N , Milde J H , Michenfelder J D
Published: June 2011

We examined the 21-aminosteroid U74006F, a potent inhibitor of lipid peroxidation, for potential neuroprotective effects in a canine model of complete cerebral ischemia. Two 1.5-mg/kg boluses were administered to six dogs, the first bolus 15 minutes prior to a 12-minute episode of complete cerebral ischemia and the second bolus after 11 minutes of ischemia, 1 minute prior to reperfusion. Using this dosage regimen, plasma U74006F levels of greater than 0.3 microgram/ml were maintained for up to an hour postischemia. An additional six animals received equal volumes of the citrate vehicle solution. At 24 and 48 hours postischemia, the dogs were neurologically evaluated by an observer blinded as to treatment selection. All six U74006F-treated animals had a normal neurologic outcome at 48 hours postischemia, while the citrate vehicle-treated animals all suffered moderate to severe neurologic deficits. The difference in outcome was significant at both 24 and 48 hours (p less than 0.005). Although U74006F is a 21-aminosteroid, it is not reported to possess glucocorticoid activity. This is supported by the present finding that no changes in plasma glucose concentration were observed following administration of the drug. The systemic vitamin E levels of citrate vehicle-treated animals decreased significantly (from 4.10 +/- 0.46 micrograms/ml to 2.95 +/- 0.38 micrograms/ml, p less than 0.05), whereas the vitamin E levels in U74006F-treated animals did not decrease significantly. These results suggest that U74006F may be of benefit in improving neurologic outcome when administered prior to an episode of complete cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of perinatal stroke on striatal amino acid efflux in rats studied with in vivo microdialysis.
Authors: Gordon K E , Simpson J , Statman D , Silverstein F S
Published: June 2011

We used in vivo microdialysis to determine the impact of a focal hypoxic-ischemic insult on striatal amino acid efflux in the immature brain. Microdialysis probes were inserted into the right striatum of postnatal day 7 rats. To induce hypoxic-ischemic injury, the right carotid artery was ligated and the animals were exposed to 8% oxygen for 2.5 hours (n = 22). Rats exposed to ligation alone (n = 10) or hypoxia alone (n = 8) and untreated controls (n = 17) were also studied. Two hours after probe insertion, a 30-minute baseline microdialysis sample was obtained. After arterial ligation, two additional baseline samples were collected. Five more samples were collected over the next 2.5 hours (in 8% oxygen or room air). Eight amino acids (glutamate, aspartate, taurine, glutamine, alanine, serine, glycine, and asparagine) were consistently detected in dialysates using a high-performance liquid chromatography assay with electrochemical detection. In untreated controls, amino acid efflux did not change over 4 hours. During hypoxia-ischemia, efflux values fluctuated widely, with marked intra-animal and interanimal variability. Efflux peaks for each amino acid were defined as values greater than the highest control mean value plus two standard deviations. Glutamate efflux peaks (greater than 7 pmol/min compared with 2 pmol/min at baseline) were detected in no controls and in eight hypoxic-ischemic rats (p = 0.006, Fisher's two-tailed exact test). Taurine efflux peaks (greater than 75 pmol/min compared with 10 pmol/min for controls at baseline) were detected in 10 hypoxic-ischemic rats and one control (p = 0.01) and in seven of the eight animals in which glutamate efflux peaks occurred (p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)
Microinfarction in classic migraine? A study with magnetic resonance imaging findings.
Authors: Ferbert A , Busse D , Thron A
Published: June 2011

By means of magnetic resonance imaging we investigated a total of 45 patients suffering from classic migraine; 25 patients had been treated in our department for classic migraine over the past 2 years (group A), and 20 other patients investigated between 1976 and 1984 were reexamined for this study (group B). Thirty-two age- and roughly sex-matched healthy volunteers underwent magnetic resonance imaging and served as controls (group C). There was a trend for patients with classic migraine to have more subcortical patchy lesions on T2-weighted magnetic resonance imaging. In a comparison of our control subjects and patients with a history of greater than 20 attacks of classic migraine taken from groups A and B, this difference in number of lesions was significant (p = 0.02). The results suggest that patchy lesions in patients with classic migraine should be interpreted with particular caution before diagnosing a demyelinating disease since the lesions could be ischemic in origin.
Remote cortical dysfunction in aphasic stroke patients.
Authors: Demeurisse G , Verhas M , Capon A
Published: June 2011

We studied the effect of deep-seated left hemispheric lesions on cortical blood flow in 18 right-handed aphasic stroke patients. Regional cerebral blood flow was measured at rest and during the performance of a functional naming test using the two-dimensional xenon-133 inhalation method. Compared with 10 controls, at rest the patients showed regional cortical hypoperfusion in the left frontoparietal region. In the controls, activation patterns from the rest to the test condition involved mainly the left hemisphere areas. In the patients, a lack of blood flow change was observed in several areas that were usually hypoperfused at rest. However, in patients with slight verbal expression disorders there were obvious blood flow increases in other brain regions in both hemispheres. Such cortical functional reorganization and the presence of a remote cortical dysfunction could play a role in the pathophysiology of language disorders.
Platelet emboli in rat brain cross when the contralateral carotid artery is occluded.
Authors: Tietjen G E , Futrell N , Garcia J H , Millikan C
Published: June 2011

The pathogenesis of embolic events ipsilateral to an occluded carotid artery is uncertain. To examine this question we combined occlusion of the left common carotid artery with embolism from the right common carotid artery in rats. Following ligation of the left carotid artery in 20 experimental rats, we irradiated the right carotid artery with a laser (632 nm, 200 mW/cm2, 12-15 minutes) following the intravenous injection of 12.5 mg/kg of the photosensitizing agent Photofrin II. Controls had left carotid artery occlusion with (n = 13) or without (n = 6) Photofrin II. Fifteen of the 20 experimental rats survived to be perfused at 24 hours; cerebral infarcts were identified in 12 rats, with bilateral infarcts in 10. There were 112 infarcts (101 small [less than 2.5 mm] and 11 large [greater than 2.5 mm] on the right and 103 (93 small and 10 large) on the left. Emboli were seen in association with some infarcts and were evenly distributed in the two hemispheres (37 emboli on the right and 40 on the left, with the midline azygous artery occluded in four animals). Left carotid artery occlusion did not produce infarcts or emboli in the controls. We conclude that cerebral infarcts in the distribution of an occluded common carotid artery may be caused by emboli from the contralateral carotid artery in rats.
Lack of effect of PN 200-110 on neuronal injury and neurological outcome in middle cerebral artery-occluded rats.
Authors: Marinov M , Wassmann H
Published: June 2011

We evaluated the influence of a continuous intravenous infusion of 0.24 mg/kg PN 200-110 started 20 minutes before the induction of ischemia and continued for 2 hours on infarct size, histopathology, and neurological outcome in middle cerebral artery-occluded rats treated with PN 200-110 (n = 8), placebo (n = 7), or saline (n = 8). Neurological examination was performed 24 hours after occlusion. We quantified infarct size by 2,3,5-triphenyl-tetrazolium chloride, hematoxylin and eosin, and Nissl staining and by computerized analysis of tracings of the infarcted areas and evaluated neuronal injury at the infarct periphery. The different types of ischemic cell damage were quantified by direct visual counting. We found no differences among saline-, placebo-, and PN 200-110-treated rats regarding infarct size, amount of neuronal alteration, and neurological outcome. Our results indicate the lack of a significant protective effect of this drug in experimental focal ischemia.
Regression of carotid plaques during low density lipoprotein cholesterol elimination.
Authors: Hennerici M , Kleophas W , Gries F A
Published: June 2011

We performed serial prospective ultrasound examinations of four flat and 17 soft carotid plaques during an average of 17 months in seven patients with heterozygous hypercholesterolemia during heparin-induced extracorporeal low density lipoprotein elimination on precipitation from plasma. By means of a specially designed quantitative three-dimensional ultrasound analysis, significant plaque volume reduction could be evaluated in all subjects, along with a marked reduction of total and low density lipoprotein cholesterol and fibrinogen serum levels.
An autopsy study of the incidence of lacunes in relation to age, hypertension, and arteriosclerosis.
Authors: Dozono K , Ishii N , Nishihara Y , Horie A
Published: June 2011

We investigated selected features of lacunes in 1,086 necropsy cases. Lacunes were found in brains from patients above the age of 40 years and were most common in brains from persons in their sixties but decreased in number in brains from older persons. The most common site of lacunes was the frontal lobe white matter, followed by the putamen, pons, parietal lobe white matter, thalamus, and caudate nucleus in descending order of frequency. By dividing the 1,086 cases into three groups according to blood pressure, we found more lacunes in the hypertensive and borderline hypertensive groups than in the normotensive group; the average number of lacunes per brain in each group was 3.61, 2.77, and 1.15, respectively. Diastolic hypertension was more closely related to the number of lacunes than was systolic hypertension. The extent of arteriolosclerosis of the medullary arteries in the frontal lobe white matter was measured and compared with the number of lacunes. There was a close correlation between lacunes and arterioloslerosis in all age groups.
Basilar branch pontine infarction with prominent sensory signs.
Authors: Helgason C M , Wilbur A C
Published: June 2011

We identified 10 patients with acute pontine infarction and specific sensory findings. Two patients had pure sensory symptoms, two had sensory complaints of the hand and mouth, and the other six had hemisensory loss referable to medial lemniscal or spinothalamic tract dysfunction but localized to one limb, to an arm and leg, or to the face, characteristic of stroke localized to the cerebral hemisphere. All patients had magnetic resonance imaging showing infarction of the medial or lateral pontine tegmentum and a patent basilar artery. No definite source for cardiogenic thromboembolism was found. Infarcts in the midline extending from the base of the pons posteriorly into the tegmentum suggested basilar branch occlusion, while infarcts involving only part of the tegmentum probably resulted from small penetrator branch occlusion. Vertigo, light-headedness, or cranial nerve dysfunction suggested a pontine location of neurological dysfunction in these patients, but the nature of the sensory findings did not always predict the lateral, medial, inferior, or superior extent of tegmental infarction.
Severe anemia associated with transient neurological deficits.
Authors: Shahar A , Sadeh M
Published: June 2011

In two patients with carotid artery stenosis and anemia, neurological deficits appeared whenever the hemoglobin level fell below a critical level of 5-6 g/dl and resolved with correction of the anemia. Profound anemia should be considered as a cause of focal neurological deficit, especially if there is evidence of cerebral atherosclerosis.
A comparison of transcranial Doppler and cerebral blood flow studies to assess cerebral vasoreactivity.
Authors: Dahl A , Lindegaard K F , Russell D , Nyberg-Hansen R , Rootwelt K , Sorteberg W , Nornes H
Published: June 2011

The aim of this study was to determine the ability of transcranial Doppler ultrasonography when used to assess cerebral vasoreactivity. The results of this method were compared with regional cerebral blood flow measurements.

Forty-three patients with symptoms suggesting cerebrovascular disease took part. Transcranial Doppler findings in the middle cerebral arteries were compared with regional cerebral blood flow in the corresponding perfusion territories before and after acetazolamide administration.

There was a significant positive correlation between the absolute increase in cerebral blood flow in milliliters per 100 g per minute and the percent increase in velocity (r = 0.63). The right-left, side-to-side difference of the acetazolamide response obtained by the two methods also showed a positive correlation (r = 0.80). Control limits obtained from healthy subjects were used for both the blood flow increase (absolute values and asymmetry in absolute values) and the velocity increase (percent increase and asymmetry in percent increase). The two methods then agreed in their evaluation of vasoreactivity in 74 (86%) of the 86 middle cerebral artery perfusion territories; 20 (23%) were assessed by both methods as having a reduced vasodilatory reserve. Eleven hemispheres with a slightly reduced regional cerebral blood flow response to acetazolamide were not detected by transcranial Doppler, whereas all territories with a marked reduction were identified by Doppler. Only one hemisphere with a normal cerebral blood flow increase after acetazolamide administration was assessed by Doppler as having reduced vasoreactivity.

Transcranial Doppler and the acetazolamide test may be used in clinical situations to assess cerebral vasoreactivity.
Stroke incidence in Copenhagen, 1976-1988.
Authors: Lindenstrøm E , Boysen G , Nyboe J , Appleyard M
Published: June 2011

Temporal trends in stroke incidence in Denmark have not been previously reported. The Copenhagen City Heart Study is a prospective study based on a randomly selected sample of an urban population of, initially, 19,698 participants followed since 1976. Over a period of 12 years, we studied three important aspects of stroke incidence in 848 identified cases: temporal trends, dependence on age and sex, and comparison of responders and nonresponders.

The participants were invited to two health examinations at 5-year intervals. The participants who attended at least one of the two examinations are termed responders and those who attended none nonresponders. The cases of first-ever stroke were collected from responders, the National Patient Register, and the National Register of Deaths and were verified by study of hospital records and death certificates.

For responders aged 35-64 years and greater than or equal to 65 years, there were no significant changes in the weighted rates in four consecutive 3-year periods. There was a tendency toward decreasing rates among younger women, but not in older women or men. The age- and sex-adjusted rates per 1,000 (based on the Danish population in 1982) in responders in the entire 12-year follow-up period were 1.61 in women, 2.67 in men, and 2.14 in both sexes combined. Stroke incidence rates increased exponentially with age in both sexes, with rates in men generally twice those in women, even in the greater than or equal to 75 years of age group. Age-adjusted rates were higher in nonresponders than in responders. For women, this ratio was 1.7; for men, 1.1.

The stroke incidence in Copenhagen is relatively high and has shown no decreasing tendency over the period 1976-1988.
Effect of 33% xenon inhalation on whole-brain blood flow and metabolism in awake and fentanyl-anesthetized monkeys.
Authors: Yao L P , Bandres J , Nemoto E M , Boston J R , Darby J M , Yonas H
Published: June 2011

Despite the documented diagnostic value of local cerebral blood flow maps by xenon-enhanced computed tomography, reports of cerebral blood flow activation by inhaled 33% Xe raised concerns about the method's safety and accuracy. We evaluated the effect of 33% Xe inhalation on cerebral blood flow and cerebral metabolic rates for oxygen and glucose in four awake and six fentanyl-anesthetized rhesus monkeys.

Platinum microelectrodes and catheters in the torcular Herophili were used to measure cerebral blood flow by hydrogen clearance, and oxygen and glucose concentrations. Cerebral variables were measured after 5 and 35 minutes of exposure to room air followed randomly by 67% O2 in 33% N2 or Xe. Five- and 35-minute measurements were combined because the duration of exposure had no effect.

In awake monkeys, 33% Xe compared with 33% N2 reduced (p less than 0.05) cerebral blood flow from 75 +/- 12 to 66 +/- 9 (mean +/- SD) ml.100 g-1.min-1 and oxygen consumption from 6.1 +/- 0.7 to 5.1 +/- 0.6 ml.100 g-1.min-1. In fentanyl-anesthetized monkeys, cerebral variables during 33% N2 versus 33% Xe were cerebral blood flow, 84 +/- 26 versus 79 +/- 23 ml.100 g-1.min-1; oxygen consumption, 5.0 +/- 0.7 versus 4.9 +/- 0.5 ml.100 g-1.min-1; and glucose consumption, 8.4 +/- 1.9 versus 7.9 +/- 2.0 mg.100 g-1.min-1.

In awake monkeys, 33% Xe reduced rather than activated cerebral blood flow and oxygen consumption by 12% and 16%, respectively; it had no effect in fentanyl-anesthetized monkeys.
Effect of calcium antagonists on postischemic protein biosynthesis in gerbil brain.
Authors: Xie Y , Seo K , Ishimaru K , Hossmann K A
Published: June 2011

Prolonged inhibition of protein synthesis precedes delayed neuronal death in the CA1 sector of the hippocampus after transient cerebral ischemia. Organic calcium antagonists have been recommended for alleviation of ischemic neuronal damage. The present study was undertaken to investigate whether these drugs improve the recovery of protein biosynthesis after interruption of cerebral blood flow.

Cerebral protein synthesis was measured biochemically and autoradiographically in gerbils submitted to 5 minutes of bilateral occlusion of the common carotid arteries followed by 2 hours or 2 days of recirculation. Flunarizine (25 mg/kg) or nimodipine (1.5 mg/kg) were applied intraperitoneally shortly after ischemia.

Treatment with either calcium antagonist did not markedly influence postischemic recovery of protein synthesis in the resistant regions of the brain and did not prevent the persisting inhibition in the vulnerable stratum pyramidale of the CA1 sector of the hippocampus.

The postischemic application of the organic calcium antagonists nimodipine and flunarizine does not promote postischemic recovery of protein synthesis. The beneficial effects of these drugs must, therefore, be based on other mechanisms.
Infarct reduction by the platelet activating factor antagonist apafant in rats.
Authors: Bielenberg G W , Wagener G , Beck T
Published: June 2011

Recent findings suggest a key role for platelet activating factor in neuroinjury. For this reason we evaluated the effects of the platelet activating factor antagonist apafant (4-(2-chlorophenyl)-9-methyl-2[3(4-morpholinyl)-3-propanol-1- yl[6H-thieno[3.2-f[[1.2.4]triazolo]4,3-1]]1.4]diazepine on farct volume and local cerebral blood flow following irreversible occlusion of the left middle cerebral artery in rats to assess the direct and vascular components of apafant's action.

We measured infarct volume 48 hours after middle cerebral artery occlusion. The effect of multiple doses of apafant (30 mg/kg p.o.) was tested in both pretreatment (n = 8) and posttreatment (n = 8) groups. In the pretreatment group apafant was given 30 minutes before and 2, 6, and 18 hours after occlusion. Rats of the posttreatment group received apafant 1, 6, and 18 hours after middle cerebral artery occlusion. We also examined the effect of a single dose of apafant given 30 minutes prior to occlusion (n = 9) on local cerebral blood flow determined 2 hours after middle cerebral artery occlusion.

Both regimens of apafant effectively decreased infarct volume. The reduction in cortical infarct volume was 59% (p less than 0.01; H test, U test) when the rats were treated before and after vessel occlusion whereas the decrease was 47% (p less than 0.05; H test, U test) when treatment began 1 hour after occlusion. Apafant did not change local cerebral blood flow after occlusion compared with controls.

We suggest that the cytoprotection afforded by apafant occurs mainly via a direct effect on brain tissue and has no major vascular component.
Hematogenous factors and prediction of delayed ischemic deficit after subarachnoid hemorrhage.
Authors: Ameriso S F , Wong V L , Ishii H , Quismorio F P , Giannotta S L , Meiselman H J , Fisher M
Published: June 2011

Delayed ischemic deficits contribute to the high morbidity and mortality rates associated with subarachnoid hemorrhage. We evaluated the potential usefulness of measuring coagulation and hemorheological variables and cardiolipin antibodies for prediction of delayed ischemic deficit after subarachnoid hemorrhage.

Consecutive patients with subarachnoid hemorrhage were studied. Coagulation and hemorheological variables and cardiolipin antibodies were measured on admission, within 7 days of subarachnoid hemorrhage. A subset of patients was studied on admission and at two subsequent occasions.

Sixty-nine patients were studied. Sixty-one of these were without clinical manifestations of vasospasm at admission, and 16 developed delayed ischemic deficit during their hospitalization. None of the laboratory variables measured were significantly different between patients with or without later development of delayed ischemic deficit. Elevation of the fibrin fragment D-dimer was found in the group of eight patients admitted with ischemic symptoms and in 49% (34 of 69) of all patients, but this was not associated with delayed ischemic deficit. Sixteen patients were studied on three occasions; this group showed a significant decrease in hematocrit, an increased white blood cell count, and no change in fibrinogen concentration. Fibrin D-dimer levels rose significantly after surgery (from 5.01 +/- 0.69 to 5.53 +/- 0.58 ln-ng/ml, p less than 0.025) and after onset of delayed ischemic deficit (from 4.71 +/- 0.64 to 5.84 +/- 0.34 ln-ng/ml, p less than 0.01).

Hemostatic measurements, hemorheological variables, and cardiolipin immunoreactivity did not predict delayed ischemic deficit in this population.
Effect of diabetes mellitus on responses of the basilar artery in rats to products released by platelets.
Authors: Mayhan W G
Published: June 2011

Aggregation and adherence of platelets to vascular endothelium are increased during diabetes mellitus, and thus responses of cerebral arteries to products released by platelets may have important implications for the pathogenesis of stroke during diabetes. The goal of this study was to determine whether responses of the basilar artery to products released by platelets are altered during diabetes.

A craniotomy was performed over the ventral medulla to expose the basilar artery. Diameter of the basilar artery was measured using intravital microscopy in nondiabetic and diabetic (50-60 mg/kg i.p. streptozotocin) rats in response to adenosine 5'-diphosphate, serotonin, and the thromboxane analogue U-46619.

Topical application of 10 and 100 microM adenosine 5'-diphosphate produced only minimal changes in diameter of the basilar artery that were similar in nondiabetic and diabetic rats (p greater than 0.05). At 0.01, 0.1, and 1.0 microM serotonin produced dose-related constriction of the basilar artery that was similar in nondiabetic and diabetic rats (p greater than 0.05). At 0.1 and 1.0 microM U-46619 also produced similar dose-related constriction of the basilar artery in nondiabetic and diabetic rats (p greater than 0.05).

These findings suggest that responses of the basilar artery to products released by platelets are not altered by diabetes mellitus. Thus, it does not appear that alterations in reactivity of the basilar artery to products released by platelets contribute to the pathogenesis of stroke during diabetes.
Glucose-associated alterations in ischemic brain metabolism of neonatal piglets.
Authors: Laptook A R , Corbett R J , Arencibia-Mireles O , Ruley J
Published: June 2011

During global brain ischemia or hypoxia-ischemia in adults, hyperglycemia is deleterious to the brain. In contrast, similar adverse effects have not been found in neonatal animals. This investigation examined neonatal piglets to determine if there were specific alterations of ischemic brain metabolism associated with different systemic glucose concentrations and to potentially clarify the effects of hyperglycemia during ischemia in neonates.

Two groups of animals (n = 12 in each group) were studied during partial ischemia to compare the effects of hyperglycemia (plasma glucose concentration, 258 +/- 97 mg% [mean +/- SD]) with modest hypoglycemia (plasma glucose concentration, 62 +/- 23 mg%). A broad spectrum of cerebral blood flow reduction was achieved by combining inflation of a cervical pressure cuff with varying degrees of hemorrhagic hypotension. High-energy phosphorylated metabolites, intracellular pH, and cerebral blood flow were simultaneously measured using a magnetic resonance spectroscopic technique. Brain metabolic variables (beta-ATP, inorganic phosphorus, phosphocreatine, intracellular pH) were plotted as a function of blood flow reduction during partial ischemia for each group.

During ischemia values of cerebral blood flow were comparably distributed between groups and ranged from 15% to 110% of those of control. At a given reduction of cerebral blood flow, hyperglycemic piglets maintained a higher concentration of beta-ATP (p = 0.011) and had a smaller increase in inorganic phosphorus (p less than 0.001). At cerebral blood flow less than 50% of control, the intracellular pH of piglets with modest hypoglycemia during partial ischemia was never reduced to less than 6.46, whereas intracellular pH fell as low as 5.97 for hyperglycemic animals.

ATP preservation may account for the differing effects of glucose during ischemia in neonates compared with adults, provided that the accentuated brain acidosis is not deleterious to neonatal brain tissue.
Bilateral medial medullary infarction with oculomotor disorders.
Authors: Toyoda K , Hasegawa Y , Yonehara T , Oita J , Yamaguchi T
Published: June 2011

We describe the first case of bilateral medial medullary infarction demonstrated by magnetic resonance imaging. We discuss the relation between this lesion and the oculomotor signs that were observed clinically.

A 71-year-old man initially presented with pure motor hemiparesis, which progressed to complete quadriplegia. He also developed nearly complete vertical and horizontal ophthalmoplegia. Magnetic resonance imaging revealed upper medial medullary infarctions bilaterally that extended to the pontomedullary junction.

We propose that the vertical oculomotor disorders resulted from involvement of the oculomotor system in the caudal brain stem, especially the caudal paramedian pontine reticular formations on both sides.