bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arterial enlargement in the atherosclerosis risk in communities (ARIC) cohort. In vivo quantification of carotid arterial enlargement. The ARIC Investigators.
Authors: Crouse J R , Goldbourt U , Evans G , Pinsky J , Sharrett A R , Sorlie P , Riley W , Heiss G 
Published: June 2011

The relation between arterial wall (intimal-medial) thickness and lumen narrowing is complex and has previously been studied predominantly at autopsy. B-mode ultrasound affords the opportunity to visualize both wall and lumen of the extracranial carotid arteries in vivo. Several studies have quantified the relation of various independent variables to wall thickness of carotid arteries in population-based samples, but the relation of age and wall thickness to interadventitial and lumen diameter has not previously been investigated in these samples.
We used B-mode ultrasound to quantify the relation of arterial lumen diameter to age, arterial wall thickness, and arterial size (interadventitial diameter) of the extracranial carotid artery in 13,711 members of the Atherosclerosis Risk in Communities (ARIC) cohort.
Men had greater interadventitial diameters, thicker walls, and wider lumens than women. Wall thicknesses of the common carotid artery were greater by 21% in men and 22% in women aged 60 to 64 years compared with those aged 45 to 49 years (P < .001). However, lumen diameters were also greater in older individuals because interadventitial diameters were greater. Wall thickness of the internal carotid artery was also associated positively with age, but the lumen diameter of the internal carotid artery was smaller in older individuals. Diameters of the carotid artery segments also differed in their relation to arterial wall thickening. The lumen of the internal carotid artery was uniformly progressively narrower with increasing wall thickness. For the common carotid artery greater wall thickness bore only a small correlation with narrower lumen diameter for thickening of the arterial wall up to 1.2 mm, but the association was more marked for the range of thicknesses between 1.2 mm and 2.5 mm.
When arterial enlargement accompanies increased wall thickness, less lumen constriction results than expected. Quantification of these complex relations in vivo may provide new insight into the pathogenesis of symptoms related to vascular disease. Narrowing of the internal carotid artery lumen associated with thicker walls is consistent with the observation that stenosis develops in this region and often leads to symptoms.
Intracranial blood flow velocities in acute ischemic stroke.
Authors: Alexandrov A V , Bladin C F , Norris J W 
Published: June 2011

Transcranial Doppler sonography (TCD) can evaluate noninvasively the blood flow velocities and patency of the main trunk of the middle cerebral artery (MCA). Using TCD we evaluated MCA patency and patterns of flow through the circle of Willis in patients with acute stroke.
Patients with symptoms of hemispheric stroke were evaluated with serial TCD tests during admission. The Canadian Neurological Scale was used to assess neurological deficits. In all cases computed tomographic scan, 99mTc hexamethylpropyleneamine oxime single-photon emission computed tomography, and carotid duplex were performed, and in some cases cerebral angiography.
Seventy-five consecutive patients with symptoms of acute ischemic stroke (mean time, 8 +/- 4 hours) were studied. Four circle of Willis perfusion patterns were observed: normal, collateral, stenotic, and occlusive. MCA occlusion or stenosis was seen in 70% of initial TCD studies in the stroke group (n = 50) but not in patients with transient ischemic attacks (n = 25). Eighty-six percent of the initial MCA occlusions had recanalized by 2 weeks after onset. Four patients, evaluated within the first 4 hours after onset, illustrated different patterns of MCA flow. TCD findings were compared with cerebral angiography, computed tomography, and single-photon emission computed tomography.
TCD allows early differentiation of patency and natural history of MCA thromboembolic events. This may have important implications in the decision for thrombolytic therapy.
Glucose given after hypoxic ischemia does not affect brain injury in piglets.
Authors: LeBlanc M H , Huang M , Patel D , Smith E E , Devidas M 
Published: June 2011

Giving glucose before hypoxic ischemia worsens brain injury in piglets. Does giving glucose after hypoxic ischemia affect severity of injury?
Forty-three 0- to 3-day-old pigs were used. All piglets received 2 U/kg insulin before injury to prevent stress-induced hyperglycemia. Hypoxic ischemic brain damage was induced by clamping both carotid arteries and reducing arterial blood pressure to two thirds of normal by hemorrhage at time 0. At 15 minutes the fraction of inspired oxygen (FIO2) was reduced to 6%. At 30 minutes FIO2 was increased to 100%, the carotids were released, and the withdrawn blood was reinfused. The piglets were then randomized to receive either 2 mL/kg of 50% dextrose followed by 2 mL/kg per hour for 2 hours or an equal volume of saline.
Neurological examination scores (20 is normal, 5 is brain dead, by blinded observer) at 1 day postinjury were similar in the two groups: glucose, median 15.5 (25th percentile, 12.2; 75th percentile, 18); controls, 15.6 (9.3, 18). Piglets were killed at 3 days with brain preservation at death. Pathological examination scores (sum of scores from cortex, hippocampus, and basal ganglia: 30 is normal, 3 is total necrosis) by blinded observer were similar in the two groups: glucose, 26 (18, 28); controls, 25 (16.5, 28); NS.
Although elevated glucose levels during hypoxic ischemic injury worsen brain injury in the piglet, elevated glucose levels after injury do not affect the severity of the injury.
Tumor necrosis factor-alpha expression in ischemic neurons.
Authors: Liu T , Clark R K , McDonnell P C , Young P R , White R F , Barone F C , Feuerstein G Z 
Published: June 2011

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine with diverse proinflammatory actions, including endothelial leukocyte adhesion molecule expression. Since leukocytes infiltrate into ischemic brain lesions, the present study was conducted to examine whether TNF-alpha messenger RNA (mRNA) and peptide are expressed in the brain after experimental focal stroke and before leukocyte accumulation.
TNF-alpha mRNA and protein expression were monitored in the ischemic and nonischemic cerebral cortex of rats after focal ischemia produced by permanent middle cerebral artery occlusion. The effect of TNF-alpha administered by microinjection into the brain cortex on leukocyte adherence to brain capillaries was also studied.
Induction of TNF-alpha mRNA, normalized to a standard reference rat macrophage TNF-alpha mRNA, was detected as early as 1 hour after middle cerebral artery occlusion. TNF-alpha mRNA was elevated by 3 hours (29 +/- 6% versus 2 +/- 1% in sham-operated rats) only in the ischemic cortex, with peak expression at 12 hours (104 +/- 8%; P < .01). Five days after middle cerebral artery occlusion, TNF-alpha mRNA levels in ischemic cortex were still significantly elevated (38 +/- 5%; P < .05). Also, TNF-alpha mRNA expression was greater in the ischemic cortex of spontaneously hypertensive rats than in normotensive rats (P < .05). Double-labeling, immunohistochemical studies revealed the presence of TNF-alpha protein localized within nerve fibers in the evolving infarct at 6 and 12 hours after ischemia and further expression in the tissues immediately adjacent to the infarct 24 hours after ischemia. After 5 days, the neuronally localized peptide had diminished greatly, but macrophages located within the infarcted tissues were immunoreactive. Cortical microinjections of TNF-alpha (10 ng in 1 microL) produced a significant neutrophil adherence/accumulation in capillaries and small blood vessels 24 hours later.
These results represent the first demonstration that focal cerebral ischemia in rats results in elevated TNF-alpha mRNA and protein in ischemic neurons. The neuronal expression of peptide appears to facilitate the infiltration of inflammatory cells that can further exacerbate tissue damage in cerebral ischemia and might contribute to increased sensitivity and risk in focal stroke.
Differentiation between gaseous and formed embolic materials in vivo. Application in prosthetic heart valve patients.
Authors: Georgiadis D , Mackay T G , Kelman A W , Grosset D G , Wheatley D J , Lees K R 
Published: June 2011

Doppler emboli detection is an established technique, but the nature of the underlying embolic material remains unclear. The intensity and spectral distribution of emboli signals could help to distinguish between signals arising from formed and gaseous emboli. We undertook this study to develop and evaluate a differentiation algorithm based on the spectral characteristics of emboli signals. Subsequently the algorithm was applied to patients with mechanical prosthetic cardiac valves.
Emboli signals detected in patients with carotid disease, acute stroke, and atrial fibrillation were used as formed emboli data, and signals detected in patients undergoing cardiac catheterization studies were used as gaseous emboli data. For each embolus signal, the maximal amplitude, the sum of amplitudes, and the spectral intensity distribution were calculated. Two hundred emboli signals from each category were used to develop a differentiation algorithm, which was subsequently evaluated on 501 additional solid and 995 gaseous emboli signals. The same algorithm was used to analyze 5958 emboli signals detected in 60 patients with mechanical prosthetic valves.
The best results were obtained with an algorithm based on both the maximal amplitude and the sum of amplitudes (sensitivity, 99%; specificity, 96.5%). On subsequent evaluation, the sensitivity and specificity of the algorithm were 99.6% and 89.8%, respectively. Of the 5958 emboli signals detected in prosthetic valve patients, 92.4% were classified as gaseous.
Differentiation between gaseous and formed emboli signals, as detected by transcranial Doppler in vivo, is feasible by means of spectral analysis. Application of the differentiation algorithm in prosthetic valve patients suggests that the embolic material in these patients is gaseous. The possibility of distinguishing between different formed embolic materials with this technique remains to be evaluated.
Hypertension and risk of stroke recurrence.
Authors: Alter M , Friday G , Lai S M , O'Connell J , Sobel E 
Published: June 2011

Hypertension is a risk factor for initial stroke, but its relation to stroke recurrence is unclear. Therefore, we sought to analyze the effect of hypertension and its control on risk of stroke recurrence.
Within 1 month of onset, a population-based cohort of 662 patients from the Lehigh Valley with an initial stroke were enrolled. Hypertension was determined at enrollment by history. Blood pressure was also measured at enrollment and at each follow-up at 4- to 6-month intervals for up to 48 months (mean, 24 months). Stroke recurrence was verified by history, examination, and review of medical reports. Various criteria for control of blood pressure were defined. History of hypertension, measured blood pressure, and its control were analyzed in relation to stroke recurrence frequency using Kaplan-Meier and univariate, multivariate, and time-dependent Cox proportional hazards models.
At enrollment, 59.4% of the cohort had a history of hypertension and 81 patients had a second stroke. Those with a history of hypertension had a significantly higher stroke recurrence rate than those without such a history (P = .01). Among those with measured diastolic blood pressure at enrollment > or = 95 mm Hg, 43% had a stroke recurrence by the end of the study compared with only 19% below this cutoff (P = .005). Recurrence risk was reduced in a multivariate analysis as quality of diastolic blood pressure control increased (relative risk = 8.4, 3.9, and 2.0 among those with poor, fair, and good control, respectively, compared with nonhypertensive subjects). Systolic blood pressure and its control appeared less or not significantly associated with stroke recurrence.
History of hypertension and elevated measured diastolic pressure after the initial stroke were associated with an increased risk of second stroke. Controlling diastolic pressure substantially reduced this risk.
Trends in survival after stroke among Medicare beneficiaries.
Authors: May D S , Casper M L , Croft J B , Giles W H 
Published: June 2011

Most strokes occur among people aged 65 years and older. The increasing proportion of persons who are in this age group underlines the importance for health-care providers to be aware of trends in poststroke survival. We investigated poststroke survival trends from 1985 to 1989 among Medicare beneficiaries.
Medicare hospital claim records and enrollment data were obtained on 1 901 439 Medicare patients with a principal diagnosis of stroke occurring during the years 1985 through 1989. Cox proportional hazard techniques were used to compare the 2-year poststroke survival for strokes occurring in 1986, 1987, 1988, and 1989 relative to strokes occurring in 1985. Poststroke survival trends were examined among groups defined by age, race, region, type of stroke, and, for a 20% subset, history of stroke.
We observed a modest improvement in poststroke survival from 1985 to 1989 (1989:1985 hazard ratio, 0.96; P < .05). Trends for persons with hemorrhagic stroke showed more improvement (hazard ratio, 0.88; P < .05) than those for persons with ischemic stroke (hazard ratio, 0.98; P < .05). Improvement was also greater among persons without known prior hospitalization for stroke (hazard ratio, 0.94; P < .05) and during periods of follow-up shorter than 2 years.
The variations in poststroke survival among subgroups of the population have important implications for the quality of life of stroke survivors and for the future medical and nursing needs of these populations.
Fibrin content of carotid thrombi alters the production of embolic stroke in the rat.
Authors: Halvorsen A M , Futrell N , Wang L C 
Published: June 2011

Mechanical denudation of the endothelium of the carotid artery in animals produces a nonocclusive thrombus, but the brains of these animals have not been examined for the presence of embolic stroke.
The endothelium of the right carotid artery of 16 Wistar rats was denuded using a balloon catheter. Phosphotungstic acid hematoxylin (PTAH) staining and scanning electron micrographs of the nonocclusive thrombi in the carotid arteries were compared with those produced by photochemical methods, and brains were examined for infarcts.
Although nonocclusive thrombi were present in the carotid arteries of 4 of 4 rats killed at 4 hours and in 8 of 12 killed at 24 hours, neither cerebral infarcts nor emboli were seen in the 14 brains evaluated by light microscopy. PTAH demonstrated a high fibrin content in the thrombus produced by the endothelial denudation, with almost no fibrin seen in photochemically induced thrombi. Scanning electron microscopy confirmed dense networks of fibrin in the thrombi produced by balloon denudation.
The composition of a nonocclusive thrombus may determine the embolic potential of this thrombus. A low fibrin content in a nonocclusive platelet thrombus may enhance the embolic potential. This suggests that platelet inhibition may also be indicated in patients with carotid artery disease who are being treated with anticoagulant.
Therapeutic time window and dose response of the beneficial effects of ketamine in experimental head injury.
Authors: Shapira Y , Lam A M , Eng C C , Laohaprasit V , Michel M 
Published: June 2011

The aim of this study was to determine the time and dose response of the therapeutic effects of the N-methyl-D-aspartate receptor antagonist ketamine in experimental head injury.
Sixty-six male Sprague-Dawley rats were divided into eight groups. Groups A, B, and C were surgically prepared but received no trauma. Groups D through H received a nonpenetrating impact to the left cranium. Group A (n = 7) received no treatment. Groups B (n = 4) and C (n = 5) received 60 and 120 mg/kg IP ketamine, respectively. Group D (n = 8) received no treatment. Groups E (n = 8) and F (n = 7) received 120 and 180 mg/kg IP ketamine, respectively, 1 hour after head trauma. Groups G (n = 7) and H (n = 9) were treated with 180 mg/kg IP ketamine 2 and 4 hours after head trauma, respectively. Neurological severity score (NSS, 0 through 25 from no injury to severe injury) was determined at 1, 24, and 48 hours after head trauma. After death at 48 hours, cortical slices were taken adjacent to the lesion on the traumatized hemisphere and from comparable sites in the contralateral hemisphere for determination of tissue specific gravity and water content. Brains were then placed in 4% formaldehyde, and the volume of hemorrhagic necrosis was measured 4 days later. NSS was compared within and between groups using the Kruskal-Wallis test for repeated measurements and Mann-Whitney U test for post hoc testing. Water content, specific gravity, and hemorrhagic necrosis were compared within and between groups using two-way ANOVA followed by Fisher's protected least significant difference procedure. A value of P < .05 was considered statistically significant.
Head trauma alone increased NSS, decreased specific gravity, increased water content, and caused cerebral infarction in the injured hemisphere. Ketamine given in two time-dose regimens, 180 mg/kg IP at 2 hours (group G) and 120 mg/kg IP at 1 hour (group F) after trauma, improved NSS from 11.6 +/- 1.7 and 14.4 +/- 0.8 at 1 hour to 4.4 +/- 1.3 and 8.0 +/- 1.4 (mean +/- SEM) at 48 hours, respectively (P < .03). Compared with the untreated group (group D), 180 mg/kg IP ketamine given at 2 and 4 hours after head trauma decreased the volume of hemorrhagic necrosis from 37.1 +/- 9.5 mm3 to 10.1 +/- 3.8 and 15.3 +/- 3.6 mm3, respectively (P < .05). Brain tissue specific gravity and water content at 48 hours were not significantly different between treated and untreated groups. There was no difference in rectal and temporalis muscle temperature between groups.
We conclude that 180 mg/kg IP ketamine was effective in ameliorating neurological dysfunction after head trauma in rats when the administration time was delayed for 1 hour to 2 hours but not after 4 hours. When given at 1 hour after head trauma, ketamine at 120 mg/kg but not 60 mg/kg is effective in reducing neurological damage after head trauma.
Correlation between angiogenesis and basic fibroblast growth factor expression in experimental brain infarct.
Authors: Chen H H , Chien C H , Liu H M 
Published: June 2011

Cerebral endothelial cells are quiescent under normal conditions; they are stimulated to proliferate around an infarct, although the mechanism is unclear. In the present study we explored the relation between angiogenesis and the expression of basic fibroblast growth factor (bFGF) by participating cells in brain infarct.
Brain infarct was created in rats by ligation of a branch of the left middle cerebral artery followed by permanent occlusion of the left common carotid artery and temporary occlusion of the right common carotid artery. The brains were removed after 1 to 14 days and studied with histological and immunohistochemical methods. Bromodeoxyuridine (BRdU) was used as an S-phase marker for the proliferative cells.
Enhanced bFGF immunoreactivity was observed in neurons adjacent to the infarct after 1 day, and the change subsequently spread to distant neurons in the ipsilateral hemisphere. After 2 days blood vessels and glial cells around the infarct began to incorporate BRdU. During the first week new capillaries accompanied by macrophages extended into the infarct. The macrophages, endothelial cells, and reactive astrocytes expressed mild to moderate bFGF immunoreactivity.
The spatial and temporal correlation between bFGF expression and angiogenesis in conjunction with the well-known biological properties of bFGF suggest that bFGF produced by neurons, macrophages, and glial cells may participate in angiogenesis in brain infarct.
Reperfusion-induced injury to the blood-brain barrier after middle cerebral artery occlusion in rats.
Authors: Yang G Y , Betz A L 
Published: June 2011

The integrity of the blood-brain barrier may play an important pathophysiological role during postischemic reperfusion. To determine the factors that lead to exacerbation of brain injury by reperfusion, we investigated changes in cerebral blood flow, blood-brain barrier permeability, edema formation, and infarction in permanent or temporary middle cerebral artery occlusion in rats and studied the relation between local cerebral blood flow and blood-brain barrier disruption.
Middle cerebral artery occlusion was performed with the rat suture model, allowing either permanent (6 hours) or temporary occlusion (3 hours of occlusion and 3 hours of reperfusion). We measured brain water, ion contents, and infarct volumes and determined cerebral blood flow using laser Doppler flowmetry and blood-brain barrier permeability with [3H] alpha-aminoisobutyric acid.
During occlusion, cerebral blood flow was reduced to 7% to 15% (permanent) and 10% to 17% (temporary) of the baseline. During 3 hours of reperfusion, it returned to 47% to 80% (lateral cortex) and 78% to 98% (medial cortex) of the baseline. Compared with the contralateral hemisphere, the water content in the ischemic area increased in both permanent and temporary groups (P < .05, P < .01). Both infarct volume and blood-brain barrier disruption were greater in the reperfusion group compared with the permanent occlusion group (P < .05). Blood-brain barrier disruption correlated with cerebral blood flow during reperfusion (P < .05).
These findings demonstrate that brain infarct and blood-brain barrier disruption are exacerbated after reperfusion in this model of focal ischemia. Blood-brain barrier disruption may relate to the degree of cerebral blood flow recovery. Thus, although early reperfusion in focal ischemia may preserve penumbra tissue, late reperfusion may increase the tissue injury.
Differential effect of three cyclooxygenase inhibitors on human cerebral blood flow velocity and carbon dioxide reactivity.
Authors: Markus H S , Vallance P , Brown M M 
Published: June 2011

Prostaglandins are believed to play an important role in maintenance of cerebral blood flow and possibly in the vasodilatory response to carbon dioxide. Therefore, the nonsteroidal anti-inflammatory drugs and aspirin, which inhibit cyclooxygenase, might be expected to reduce cerebral blood flow and the response to hypercapnia. This could induce cerebral ischemia in patients with a hemodynamically critical circulation. It would also interfere with the measurement of cerebrovascular reserve using carbon dioxide.
The effect of a single dose of indomethacin and of two other cyclooxygenase inhibitors (aspirin and sulindac) on the cerebral circulation was measured using transcranial Doppler ultrasonography of the middle cerebral artery. Seven normal adults were studied in each drug group. Resting blood flow velocity and the responses to hypercapnia and to hyperventilation were measured.
Indomethacin resulted in a fall in basal middle cerebral artery flow velocity from a mean of 48.9 cm/s to 34.0 cm/s (P < .002). It also reduced the vasoconstrictor response to hypocapnia (induced by hyperventilation) from 37.5% to 20.7% (P < .003). There was a nonsignificant reduction in the vasodilatory response to 8% carbon dioxide (mean: predrug, 87.7%; postdrug, 61.0%), with marked intersubject variability. In contrast, basal middle cerebral artery velocity and vasoconstrictor and vasodilatory responses to changes in carbon dioxide were unchanged after aspirin or sulindac administration.
The lack of effect of aspirin on basal cerebral blood flow velocity and on vasodilatory reserve is reassuring; aspirin will not reduce cerebral blood flow or the response to a reduced perfusion pressure in patients with critically impaired cerebral hemodynamics. However, indomethacin should be avoided in such patients.