bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet secretory products may contribute to neuronal injury.
Authors: Joseph R , Tsering C , Grunfeld S , Welch K M
Published: June 2011

We do not fully understand the mechanisms for neuronal damage following cerebral arterial occlusion by a thrombus that consists mainly of platelets. The view that certain endogenous substances, such as glutamate, may also contribute to neuronal injury is now reasonably well established. Blood platelets are known to contain and secrete a number of substances that have been associated with neuronal dysfunction. Therefore, we hypothesize that a high concentration (approximately several thousand-fold higher than in plasma, in our estimation) of locally released platelet secretory products derived from the causative thrombus may contribute to neuronal injury and promote reactive gliosis.

We have recently been able to report some direct support for this concept. When organotypic spinal cord cultures were exposed to platelet and platelet products, a significant reduction in the number and the size of the surviving neurons occurred in comparison with those in controls. We further observed that serotonin, a major platelet product, has neurotoxic properties. There may be other platelet components with similar effect.

The hypothesis of platelet-mediated neurotoxicity gains some support from these recent in vitro findings. The concept could provide a new area of research in stroke, both at the clinical and basic levels.
Hospitalized stroke in blacks and Hispanics in northern Manhattan.
Authors: Sacco R L , Hauser W A , Mohr J P
Published: June 2011

The growing black and Hispanic populations in the United States call for studies of the rates and prognosis for cerebral infarction to help plan more focused prevention programs.

Using the Statewide Planning and Research Cooperative System, we obtained discharge data for 1,034 patients over age 39, who were hospitalized for stroke from 1983 to 1986, using four zip code areas of the ethnically mixed community of Northern Manhattan.

Stroke incidence increased with age in both men and women in all three race/ethnic groups. The age-adjusted stroke incidence per 100,000 per year for men greater than or equal to 40 years of age was 567 for blacks, 306 for Hispanics, and 351 for whites. Incidence in women greater than or equal to 40 years was 716 in blacks, 361 in Hispanics, and 326 in whites. Hypertension and diabetes were more prevalent in blacks and Hispanics with stroke, whereas whites had more ischemic cardiac disease. Crude in-hospital mortality was greater in younger blacks and Hispanics compared with whites, whereas 2-year readmission rates, overall and for stroke, were similar in the three groups.

These estimates of hospitalized stroke incidence and mortality substantiate the greater incidence of stroke in blacks and provide new data concerning Hispanics for public health planning.
Utility of late N-isopropyl-p-(iodine-123)-iodoamphetamine brain distribution in predicting outcome following cerebral infarction.
Authors: Gupta S , Bushnell D L , Mlcoch A , Eastman G , Barnes W E , Fisher S G
Published: June 2011

The purpose of this study was to determine utility of late N-isopropyl-p-(iodine-123)-iodoamphetamine distribution in predicting neurological and language outcome.

We prospectively studied 29 patients with unilateral hemispheric ischemic cerebral infarction using the neuroimaging method of single-photon emission computed tomography and the above tracer. Four different imaging measures reflecting late tracer distribution or redistribution and three measures indicative of the patients' overall neurological or language outcome at 3 months were used in the data analysis. All patients had neuroimaging within 30 days of infarction, and 14 patients were imaged within 10 days of infarction. Data analysis was performed for all patients combined and then separately on the groups imaged within 10 days of and more than 10 days after infarction.

The volume of the late image defect significantly correlated with one measure of neurological outcome in the whole group and in those imaged more than 10 days after cerebral infarction. However, these results are difficult to explain based on the present understanding of the physiology of late N-isopropyl-p-(iodine-123)-iodoamphetamine distribution.

We feel that the pattern of late N-isopropyl-p-(iodine-123)-iodoamphetamine distribution is probably not useful as an independent predictor of neurological and language outcome.
Effect of adrenergic drugs on cerebral blood flow, metabolism, and evoked potentials after delayed cardiopulmonary resuscitation in dogs.
Authors: Gervais H W , Schleien C L , Koehler R C , Berkowitz I D , Shaffner D H , Traystman R J
Published: June 2011

Epinephrine administration during cardiopulmonary resuscitation increases cerebral blood flow by increasing arterial pressure. We tested whether potential beta-adrenergic effects of epinephrine directly influence cerebral blood flow and oxygen consumption independently of raising perfusion pressure.

Four groups of seven anesthetized dogs were subjected to 8 minutes of fibrillatory arrest followed by 6 minutes of chest compression, ventricular defibrillation, and 4 hours of spontaneous circulation. Cerebral perfusion pressure was increased to approximately equivalent ranges during resuscitation by either 1) epinephrine infusion, 2) epinephrine infusion after pretreatment with the lipophilic beta-adrenergic antagonist pindolol, 3) infusion of the alpha-adrenergic agonist phenylephrine, or 4) descending aortic balloon inflation without pressor agents.

We found no difference in cerebral blood flow, oxygen extraction, or oxygen consumption during chest compression among groups. After ventricular defibrillation, depressed levels of cerebral blood flow, cerebral oxygen consumption, and somatosensory evoked potential amplitude were not different among groups.

We detected no evidence that after 8 minutes of complete ischemia, epinephrine administration during resuscitation substantially influences cerebral blood flow or cerebral oxygen consumption independent of its action of raising arterial pressure or or that epinephrine has a negative impact on immediate metabolic or electrophysiological recovery attributable to its beta-adrenergic activity.
Brain magnetic resonance imaging and neuropsychologic evaluation of patients with idiopathic dilated cardiomyopathy.
Authors: Schmidt R , Fazekas F , Offenbacher H , Dusleag J , Lechner H
Published: June 2011

We compared brain magnetic resonance imaging and neuropsychologic performance in 20 neurologically asymptomatic patients suffering from idiopathic dilated cardiomyopathy (mean age 41 [range 18-49] years) and 20 age-matched controls (mean age 38 [range 28-49] years). Patients exhibited a significantly higher rate of cerebral infarcts (20% versus 0%, p less than 0.05) and cortical (50% versus 5%, p less than 0.01) and ventricular (55% versus 15%, p less than 0.02) atrophy than controls. Accordingly, semiquantitative volumetric measurements yielded a significantly increased ventricular-to-intracranial cavity ratio in the patients (6.2 +/- 2.9% versus 4.1 +/- 1.3%, p less than 0.01). This ratio and the cortical atrophy ratings correlated positively with disease duration (r = 0.63 and 0.54, p less than 0.05). Cognitive test performance was significantly worse in patients than in controls and was most impaired in those patients with morphologic cerebral abnormalities.
Basilar artery occlusion in rats.
Authors: Wojak J C , DeCrescito V , Young W
Published: June 2011

The basilar artery is one of the three major sources of blood supply to the circle of Willis. To investigate the effects of basilar artery occlusion, we surgically exposed and coagulated the basilar artery in 25 rats. Basilar artery occlusion at any single point between the foramen magnum and the circle of Willis in 11 rats did not produce histologically detectable infarcts in the brain at 12-24 hours. Two-point occlusions of the basilar artery in 12 rats produced variable infarcts between the occlusion sites but no ischemic lesions elsewhere. After either single- or double-point occlusions, the proximal basilar artery refilled within 2-3 minutes. When the basilar artery was occluded above and below the origins of the anterior inferior cerebellar arteries, the artery segments between the occlusion points initially collapsed but refilled within 2-3 minutes in two rats. Basilar artery occlusions invariably suppressed cortical somatosensory evoked potentials by greater than 50%. Regardless of whether a brain stem infarct developed, somatosensory evoked potential amplitudes recovered to greater than baseline levels by 4 hours in seven of 17 rats and returned to baseline levels by 24 hours in every rat tested. We conclude that the occluded basilar artery receives extensive retrograde collateral blood flow and that somatosensory evoked potentials are exquisitely sensitive to basilar artery occlusion but are insensitive to whether brain stem infarcts develop.
Racial differences in cerebrovascular disease hospitalizations.
Authors: Klatsky A L , Armstrong M A , Friedman G D
Published: June 2011

We studied the relationship of race to incidence of hospitalization for cerebrovascular disease among 74,096 white and 33,041 black persons who took health examinations in a prepaid health care program. Analyses were controlled for age, sex, body mass index, coffee use, smoking, alcohol use, systolic blood pressure, and baseline disease. Blacks were at higher hospitalization risk than whites for hemorrhagic cerebrovascular disease (relative risk = 2.4, 95% confidence interval = 1.3-5.8), cerebral thrombosis (relative risk = 1.9, 95% confidence interval = 1.2-2.9), and nonspecific cerebrovascular disease (relative risk = 1.6, 95% confidence interval = 1.2-2.2) but at lower hospitalization risk for extracranial occlusive disease (relative risk = 0.4, 95% confidence interval = 0.2-0.7). Blood pressure had a similar relation to all types of cerebrovascular disease in both races, but there were disparities in the relations of other atherosclerosis risk factors to different types of cerebrovascular disease. Educational attainment had little relation to hospitalization for extracranial occlusive disease, a finding that reduces the likelihood that selection bias explains the racial disparity. These data show unexplained racial differences in the type and location of cerebrovascular disease. The differences are important in understanding the pathogenesis of cerebrovascular disease and have practical clinical implications.
Quantitative assessment of cerebral blood volume by single-photon emission computed tomography.
Authors: Sabatini U , Celsis P , Viallard G , Rascol A , Marc-Vergnes J P
Published: June 2011

We implemented a technique for measuring regional cerebral blood volume using single-photon emission computed tomography and in vivo technetium-99m-labeled red blood cells and then evaluated it in nine normal human volunteers (controls) and seven patients with bilateral occlusion or severe stenosis of the internal carotid artery. We also measured regional cerebral blood flow using single-photon emission computed tomography and intravenous xenon-133 in the same subjects. We studied regional cerebral blood flow, regional cerebral blood volume, and their ratio before and after the intravenous injection of 1 g acetazolamide. Mean +/- SD baseline regional cerebral blood volume was higher in the patients than in the controls (4.1 +/- 0.6 versus 3.2 +/- 0.3 ml/100 g, p less than 0.01), and mean +/- SD baseline regional cerebral blood flow was lower in the patients than in the controls (40.5 +/- 11 versus 55.6 +/- 11 ml/100 g/min, p less than 0.05). Acetazolamide induced similar mean +/- SD increases in regional cerebral blood volume in both the controls and the patients (0.3 +/- 0.1 and 0.3 +/- 0.2 ml/100 g), while the mean +/- SD regional cerebral blood flow reactivity was significantly less in the patients than in the controls (12.6 +/- 7.6 versus 24.5 +/- 9.6 ml/100 g/min, p less than 0.05). Our study shows that single-photon emission computed tomography can provide quantitative estimates of both regional cerebral blood volume and regional cerebral blood flow in humans.
Adventitial red blood cells produce intimal platelet accumulation in cerebral arteries of cats following subarachnoid hemorrhage.
Authors: Yamamoto Y , Clower B R , Haining J L , Asari S , Smith R R
Published: June 2011

After dividing 21 cats into three equal groups, we exposed their right middle cerebral arteries transorbitally and adventitially irrigated them with 2 ml washed red blood cells, blood plasma, or saline. To determine arterial intimal platelet accumulation in each cat, we injected [111In]oxine-labeled platelets intravenously immediately before injecting the various experimental solutions. Animals were sacrificed 2 or 4 hours following the injection of labeled platelets. Irrigation with washed red blood cells produced a significantly greater intraluminal accumulation of platelets than irrigation with saline (p less than 0.05). Plasma tended to have less of an effect on platelet accumulation than washed red blood cells, but this difference was not significant. These data suggest that the adventitial blood fraction responsible for intimal platelet accumulation in cerebral arteries following subarachnoid hemorrhage may be derived mainly from the red blood cell fraction.
Rupture of the internal elastic lamina and vascular fragility in stroke-prone spontaneously hypertensive rats.
Authors: Coutard M , Osborne-Pellegrin M
Published: June 2011

We studied a possible relation between stroke and an enhanced susceptibility to rupture of the arterial internal elastic lamina by comparing stroke-prone spontaneously hypertensive rats with spontaneously hypertensive rats, which have a very low incidence of stroke. We quantified interruptions in the internal elastic lamina in certain arteries and studied the effect of beta-aminopropionitrile, an inhibitor of cross-link formation in collagen and elastic fibers, on rupture of the internal elastic lamina and on mortality in these two substrains. To eliminate any influence of higher blood pressure in the stroke-prone rats on the parameters studied, we used antihypertensive treatment to obtain equivalent blood pressures in the two substrains. Results showed that stroke sensitivity was associated with an enhanced early spontaneous rupture of the internal elastic lamina in the caudal artery, an increased susceptibility to beta-aminopropionitrile-induced rupture of the internal elastic lamina, and earlier mortality, mainly from aortic rupture, under beta-aminopropionitrile treatment. These findings suggest that stroke-prone rats have an enhanced minor connective tissue defect that is expressed by rupture of the internal elastic lamina and may be related, at least in part, to their greater vascular fragility and increased susceptibility to stroke.
Twenty-four-hour variation of blood pressure in vascular dementia of the Binswanger type.
Authors: Tohgi H , Chiba K , Kimura M
Published: June 2011

Using a noninvasive portable blood pressure recorder, we compared 24-hour variations of blood pressure among 1) 35 patients with Binswanger-type dementia, 2) 43 with lacunar-type dementia, 3) 26 with a single lacunar stroke, and 4) 30 controls. Each group was divided into antihypertensive-treated and -untreated subgroups. Among the untreated subgroups, patients with Binswanger-type dementia had significantly greater 24-hour mean systolic blood pressures, 24-hour systolic blood pressure standard deviations, and maximal systolic blood pressure variations than the controls (p less than 0.05). Among the treated patients, blood pressure variability increased similarly in all subgroups with cerebrovascular lesions compared with the controls (p less than 0.05). The nocturnal blood pressure decreases seen in the controls were absent among both untreated and treated patients with Binswanger- or lacunar-type dementia (p less than 0.05). Our results suggest the importance of hypertension, short-term variations in blood pressure, and a sustained nighttime elevation of blood pressure for the pathogenesis of both Binswanger-type and lacunar-type dementia in patients receiving antihypertensive medication.
A mathematical model for the formation of cerebral aneurysms.
Authors: Brown N
Published: June 2011

Cerebral aneurysms are hypothesized to be acquired lesions resulting from a loss of static equilibrium in the apical region of the bifurcation, which causes the opening angle of the bifurcation to change during the cardiac cycle. Repeated dynamic cycling may disrupt wall elements in a manner analogous to a wire breaking with repeated bending and result in the formation of an aneurysm. A mathematical model that predicts the geometry of arterial bifurcations is proposed. The model predicts that the transmural pressure in the larger branch is greater than or equal to that in the smaller branch and that the larger branch makes a smaller angle with the direction of the parent artery [corrected]. Bifurcations with smaller area ratios (the sum of the luminal areas of the branches divided by the luminal area of the parent artery) have smaller opening angles. When the area ratio is 1.0, the opening angle is about 90 degrees. The model concludes that the opening angle is constant during the cardiac cycle if the fractional change in the radii of the daughter and parent arteries is the same for any increase in blood pressure and if the ratio of transmural pressures in the parent and daughter branches does not change during the cardiac cycle. Otherwise, the bifurcation is considered predisposed to the development of an aneurysm.
Time-dependent changes in cerebral choline and acetylcholine induced by transient global ischemia in rats.
Authors: Scremin O U , Jenden D J
Published: June 2011

We occluded the carotid and vertebral arteries of 12 rats for 15 minutes to measure the brain concentrations of choline and acetylcholine and cerebral blood flow at the end of the ischemic period or 15, 30, or 150 minutes after circulation was reestablished. The animals were sacrificed with microwave radiation focused to the head immediately after a brief infusion of [14C]iodoantipyrine with rapid sampling of arterial blood. Brain tissue samples were extracted with ether to separate the tracer, which was subsequently measured by liquid scintillation counting and used to calculate local cerebral blood flow. The aqueous phase was then processed for the measurement of choline and acetylcholine concentrations by gas chromatography/mass spectrometry. The results showed a large increase in tissue choline content and a decrease in tissue acetylcholine content during ischemia. During recirculation, choline levels progressively declined, reaching levels lower than those in four control rats after 150 minutes of recirculation for most brain regions. A reciprocal relation between the brain choline concentration and local cerebral blood flow was found. Acetylcholine levels showed an initial rebound to greater than control during recirculation, with subsequent normalization. Brain acetylcholine concentration was positively correlated with brain choline concentration, provided that cerebral blood flow was greater than 0.3 ml x g-1 x min-1. Because tissue free choline was depleted in most brain regions 150 minutes after transient ischemia, we speculate that prolonged ischemia may produce a greater depletion of tissue free choline with a resulting decline in tissue acetylcholine. This could play an important role in the cognitive deficit associated with vascular dementia.
Hypothermia prevents ischemia-induced increases in hippocampal glycine concentrations in rabbits.
Authors: Baker A J , Zornow M H , Grafe M R , Scheller M S , Skilling S R , Smullin D H , Larson A A
Published: June 2011

We subjected 10 New Zealand White rabbits to 10 minutes of global cerebral ischemia under either normothermic (37 degrees C) or moderately hypothermic (29 degrees C) conditions. Hippocampal concentrations of glutamate, aspartate, and glycine were monitored using in vivo microdialysis. Outcome was assessed by both neurological and neuropathologic criteria. Hypothermia afforded nearly complete protection from ischemic injury. Ischemia-induced increases in the concentrations of glutamate, aspartate, and glycine in the normothermic group (3, 12, and 3 times baseline) were strikingly attenuated in the hypothermic group. In addition, the prolonged postischemic elevation of glycine levels seen in the normothermic group was absent in the hypothermic group. These results suggest that the neuroprotective properties of hypothermia may reside, in part, in their ability to prevent increases in the extracellular concentrations of amino acids that enhance the activity of the N-methyl-D-aspartate receptor complex.
Biphasic striatal dopamine release during transient ischemia and reperfusion in gerbils.
Authors: Ahn S S , Blaha C D , Alkire M T , Wood E , Gray-Allan P , Marrocco R T , Moore W S
Published: June 2011

To clarify the nature of ischemic striatal dopamine release during the earliest periods of neuronal injury, we used chronoamperometry to measure dopamine levels every 60 seconds during various durations of ischemia in 32 gerbils. Catecholamine-selective electrodes were implanted into the brains of anesthetized gerbils subjected to 2, 5, or 10 minutes of transient forebrain ischemia or permanent forebrain ischemia. Four control animals showed a stable chronoamperometric baseline. In the six gerbils subjected to permanent ischemia, dopamine release was rapid during early ischemia and slowed with time. The four animals subjected to 2 minutes of ischemia showed minimal dopamine release. The six gerbils subjected to 5 minutes of ischemia demonstrated a noticeable dopamine release during ischemia, and three of the six developed a massive secondary dopamine release during reperfusion. All six animals subjected to 10 minutes of ischemia demonstrated a similar biphasic dopamine release twice the size of that observed in the 5-minute group. Pretreatment with pargyline in six additional gerbils subjected to 10 minutes of ischemia failed to modify significantly this biphasic pattern of dopamine release. We conclude that dopamine release occurs very early during ischemia and that its magnitude correlates with the duration of an ischemia insult. Reperfusion is associated with an even larger striatal dopamine release. This previously unreported biphasic dopamine release phenomenon may have important clinical implications in the management of cerebral ischemia.
Transhemispheric diaschisis. A review and comment.
Authors: Andrews R J
Published: June 2011

We review here the literature in both animal models and humans concerning electrical activity, blood flow, and metabolism in the hemisphere contralateral to unilateral cerebral ischemia. We analyze the data by periods based on the time from initial injury to emphasize the time course of transhemispheric diaschisis. Contralateral electrical activity, such as evoked potential amplitude, is increased in the late stages after unilateral infarction, with the data from the more acute periods being inconclusive. Contralateral blood flow changes probably depend on the magnitude of the ischemic injury, with a larger insult resulting in a decrease not seen with smaller insults. Some studies have shown a decrease in contralateral blood flow over the first week followed by a gradual return toward baseline. Most measures of contralateral metabolism show a time course similar to blood flow, that is, a decrease followed by gradual recovery. The effects of corpus callosum section on transhemispheric diaschisis are not yet established. We provide examples to show that under certain conditions, diaschisis may represent a loss of remote inhibition rather than a loss of remote facilitation, as von Monakow originally suggested. By following the contralateral changes over time, particularly during the first minutes and hours of ischemia, insight will be gained into the brain's responses remote from the focus of ischemic injury. These responses should bear a relation to the brain's defense mechanisms ipsilaterally to the region of ischemia.
Disruption of the blood-brain barrier in open and closed cranial window preparations in rats.
Authors: Mayhan W G
Published: June 2011

The goal of this study was to determine whether the severity of disruption of the blood-brain barrier during acute hypertension is similar in open and closed cranial window preparations. Intravital fluorescent microscopy and fluorescein-labeled albumin were used to evaluate disruption of the blood-brain barrier under control conditions and during acute arterial hypertension in 10 rats equipped with an open cranial window and in six rats equipped with a closed cranial window. Permeability of the blood-brain barrier was quantified by calculating the clearance of fluorescein-labeled albumin and by counting the number of microvascular leaky sites under control conditions and during acute hypertension. Pressure in cerebral venules and intracranial pressure were measured in rats equipped with an open cranial window and a closed cranial window, respectively, under control conditions and during acute hypertension. In rats equipped with an open cranial window, arterial pressure increased from 118 +/- 6 to 189 +/- 3 mm Hg (mean +/- SEM) and pial venous pressure increased from 7 +/- 1 to 22 +/- 3 mm Hg during acute hypertension induced with 30 micrograms/kg/min phenylephrine for 5 minutes. In addition, the clearance of fluorescent albumin increased from 0.11 +/- 0.03 to 1.2 +/- 0.4 ml/sec x 10(-6) and the number of microvascular leaky sites increased from 0 to 25 +/- 1 during phenylephrine infusion. In rats equipped with a closed cranial window, arterial pressure increased from 122 +/- 5 to 187 +/- 7 mm Hg and intracranial pressure increased from 3 +/- 1 to 12 +/- 1 mm Hg during the intravenous infusion of 30 micrograms/kg/min phenylephrine for 5 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)
Conjugated superoxide dismutase reduces extent of caudate injury after transient focal ischemia in cats.
Authors: Matsumiya N , Koehler R C , Kirsch J R , Traystman R J
Published: June 2011

We tested the efficacy of preischemic and postischemic systemic treatment with 30,000 units polyethylene glycol-conjugated superoxide dismutase in a reperfusion model of focal cerebral ischemia. Forty-one anesthetized cats underwent 2 hours' occlusion of the left middle cerebral artery and both common carotid arteries followed by 4 hours of reperfusion. Cats were blindly assigned to one of three groups: treatment with vehicle (10% polyethylene glycol in saline, n = 17), pretreatment with drug 3 hours before ischemia (n = 12), and posttreatment with drug at the time of reperfusion (n = 12). Size of the ischemic injury was calculated from 2,3,5-triphenyltetrazolium chloride staining. Injury in the caudate nucleus was significantly reduced with pretreatment (28 +/- 6% of ipsilateral caudate volume, mean +/- SEM) compared with the vehicle (56 +/- 8%). Posttreatment did not significantly ameliorate caudate injury (46 +/- 10%). Between the first and second hours of ischemia ipsilateral caudate blood flow determined using microspheres increased significantly from 11 +/- 4 to 16 +/- 5 ml/min/100 g with pretreatment, but blood flow remained constant throughout ischemia with vehicle (8 +/- 2 ml/min/100 g) and posttreatment (10 +/- 3 ml/min/100 g). The size of cortical injury (vehicle, 17 +/- 5%; pretreatment, 11 +/- 3%; posttreatment, 17 +/- 5% of hemispheric volume) did not differ significantly among groups. Somatosensory evoked potential recovery did not differ among groups. We conclude that pretreatment with conjugated superoxide dismutase can ameliorate the extent of injury in an end-artery region, such as the caudate nucleus, in a reperfusion model of focal ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Circadian rhythmicity of stroke onset. Intracerebral and subarachnoid hemorrhage.
Authors: Sloan M A , Price T R , Foulkes M A , Marler J R , Mohr J P , Hier D B , Wolf P A , Caplan L R
Published: June 2011

Our purpose was to describe and further understand the determinants of the time of onset of parenchymatous intracerebral hemorrhage and subarachnoid hemorrhage in patients enrolled in the Stroke Data Bank.

We analyzed the observed times of onset of intracerebral hemorrhage (n = 237 patients) and subarachnoid hemorrhage (n = 243 patients) compared with expected times of onset if the probability of onset was constant across all time intervals. We also analyzed the role of clinical features (if any) in explaining the findings.

For intracerebral hemorrhage, 52.5% of patients reported onset times between 0600 hours and 1400 hours, with peak onset between 1000 and 1200 hours (chi 2 = 62.94, df = 11, p less than 0.001). Patients with subarachnoid hemorrhage were more likely to lack a history of hypertension compared with patients who had intracerebral hemorrhage (chi 2 = 23.3, df = 1, p less than 0.001). Patients with subarachnoid hemorrhage were more likely to have more uniform onset time throughout the day (chi 2 = 12.92, df = 7, p = 0.074). However, subarachnoid hemorrhage patients with a history of hypertension were more likely to have peak onset times in mid-to-late morning compared with patients without such a history (chi 2 = 35.25, df = 10, p less than 0.001). The nonuniformity of onset times for intracerebral hemorrhage persisted even if patients with unknown onset times were treated as through their onset times were randomly distributed between 0000 and 0800 hours. Seasonal periodicity and the relation between initial systolic or diastolic blood pressure and time of onset for either type of hemorrhage were not observed.

Our data suggest that the time of onset for both intracerebral hemorrhage and subarachnoid hemorrhage patients with a history of hypertension is similar to the diurnal variation in blood pressure.
Relation between middle cerebral artery blood flow velocity and stump pressure during carotid endarterectomy.
Authors: Spencer M P , Thomas G I , Moehring M A
Published: June 2011

Many patient monitoring techniques have been used for detecting cerebral hypoperfusion during carotid endarterectomy. We compared middle cerebral artery blood flow velocities with carotid artery stump pressures to evaluate the indications for common carotid artery cross-clamp shunting and the probable hemodynamic causes of cerebrovascular complications.

Blood flow velocities were monitored with transcranial Doppler ultrasound and carotid stump pressures were measured at the time of common carotid artery cross-clamping during 97 carotid endarterectomy procedures. Stump pressures measured with the gauge zero reference at the common carotid artery level were correlated with the percentage change of velocities.

Middle cerebral artery blood flow velocities usually decreased upon common carotid artery cross-clamping, depending on collateral availability and the autoregulation response. The best fit of the data was to an exponential function concave to the pressure axis, with velocity as a percentage of the pre-cross-clamp value reaching zero at 15 mm Hg stump pressure (r = 0.85 and p less than 0.001).

There is a less critical margin of error with percentage middle cerebral artery blood flow velocity decreases than with stump pressure measurements. This relation establishes changes in middle cerebral artery blood flow velocities as a reliable parameter for judging the effects of carotid cross-clamping on cerebral blood flow and providing an excellent indicator as to the necessity for shunting.
Beneficial effect of mild hypothermia and detrimental effect of deep hypothermia after cardiac arrest in dogs.
Authors: Weinrauch V , Safar P , Tisherman S , Kuboyama K , Radovsky A
Published: June 2011

Mild cerebral hypothermia (34 degrees C) induced immediately after cardiac arrest improves outcome. Deep postarrest hypothermia (15 degrees C) has not been studied.

We used our dog model of normothermic ventricular fibrillation (no blood flow) of 12.5 minutes, reperfusion by brief cardiopulmonary bypass, controlled ventilation to 20 hours, and intensive care to 72 hours. Head surface cooling and bypass cooling were performed from start of reperfusion to 1 hour. Five groups of six dogs each were compared: group I, normothermic controls; group II, deep hypothermia (15 degrees C); group III, moderate hypothermia (30 degrees C); group IV, mild hypothermia (34 degrees C); and group V, mild hypothermia with head surface cooling begun during no flow.

In control group I, five dogs remained comatose (overall performance category [OPC] 4) and one severely disabled (OPC 3). In group II, four dogs achieved OPC 4 and two dogs OPC 3 (NS versus group I). Compared with group I, OPCs were better in group III (p less than 0.05), group IV (p less than 0.05), and group V (p less than 0.05). Neurological deficit scores were also better in groups III, IV, and V than in groups I or II (p less than 0.05). Total brain histological damage scores were better in group III (p = 0.02), group IV (p = 0.06), and group V (p less than 0.05) than in group I. In group II, OPC and neurological deficit scores were the same and histological damage scores numerically worse than in group I and all were worse than in groups III, IV, and V (p less than 0.05). Cardiovascular complications and myocardial morphological damage in groups II and III were worse than in groups I, IV, and V (p less than 0.05).

Mild or moderate cerebral hypothermia induced immediately after cardiac arrest improves cerebral outcome, more likely when initiated during arrest, whereas deep postarrest hypothermia can worsen cerebral and cardiac outcome.
Marked increase of stroke incidence in men between 1972 and 1990 in Frederiksberg, Denmark.
Authors: Jørgensen H S , Plesner A M , Hübbe P , Larsen K
Published: June 2011

Stroke incidence declined until the end of the 1970s in the United States, and the decline continued into the 1980s in Japan. The purpose of this study was to determine possible temporal changes of stroke incidence in a European community.

A prospective stroke registry was established in the community of Frederiksberg (population, approximately 90,000), Denmark, in the two periods 1972-1974 and 1989-1990. All patients suspected of stroke were clinically evaluated by a neurologist. Only patients with first-ever stroke were included. Complete case ascertainment was ensured by registration of both hospitalized and nonhospitalized patients. Death certificates were also scrutinized.

A total of 927 patients with first-ever stroke was recorded. The annual stroke incidence rate per 1,000 increased by 18% from 2.6 in 1972-1974 to 3.1 in 1989-1990 (p < 0.01). This increase was due solely to a 42% increase in men, in whom stroke incidence rose from 2.1 to 3.0 (p < 0.0005). Incidence was unchanged in women at 3.0 and 3.1, respectively. The incidence rates from 1972-1974 were age and sex adjusted to the 1990 population. After adjustment to the Danish population, stroke incidence in Denmark was 2.0 for all, 2.3 for men, and 1.9 for women. In the second study period computed tomography or necropsy was performed in 85% of cases; 2.4/1,000 had cerebral infarction; 0.20/1,000 had intracerebral hemorrhage; and 0.02/1,000 had subarachnoid hemorrhage.

In a period when decline in stroke incidence has stopped in the United States and has continued in Japan, a marked increase of stroke incidence in Danish men was observed.
Selective brain cooling during and after prolonged global ischemia reduces cortical damage in rats.
Authors: Kuluz J W , Gregory G A , Yu A C , Chang Y
Published: June 2011

Studies of the cerebroprotective effects of selective brain cooling have failed to show amelioration of ischemic injury in the cerebral cortex. This study was designed to test the hypothesis that mild-to-moderate selective brain cooling initiated after the onset of global brain ischemia in rats protects the cerebral cortex and improves neurological outcome.

Global forebrain ischemia for 30 minutes in 27 fasted adult male Wistar rats was achieved by bilateral carotid occlusion and hypotension. In group 1, brain temperature, measured in the temporalis muscle, was maintained at 37-38 degrees C throughout the experiment. In group 2, brain temperature fell spontaneously during ischemia to 34.7 +/- 0.1 degrees C and rose spontaneously to 36-37 degrees C after 10 minutes of recirculation. In group 3, brain temperature was lowered with ice packs placed around the head after 15 minutes of ischemia to 24.1 +/- 0.9 degrees C by the end of ischemia, maintained at 30.0 +/- 1.0 degrees C for the first hour of recirculation, then allowed to rise to 36-37 degrees C.

Seven-day survival was 0% (0 of 6) in group 1, 73% (8 of 11) in group 2, and 100% (6 of 6) in group 3. Severity of neuronal damage was less in group 2 than in group 1 in the cortex (p < 0.05) and hippocampal CA1 (p < 0.05) and CA3 regions (p < 0.05). Group 3 had less neuronal damage than group 2 in both cortex (p < 0.02) and striatum (p < 0.02). Furthermore, postischemic weight loss was less and neurobehavioral scores were significantly higher in group 3.

This study shows that selective brain cooling increases survival from prolonged global ischemia and reduces neuronal injury in the cerebral cortex as well as the striatum and hippocampus.
Extracellular alkalinity exacerbates injury of cultured cortical neurons.
Authors: Giffard R G , Weiss J H , Choi D W
Published: June 2011

We have previously shown that extracellular acidity protects cultured fetal murine neocortical neurons from glutamate toxicity and combined oxygen-glucose deprivation injury, an action at least in part mediated by reduction in N-methyl-D-aspartate receptor activation. We now investigate the effect of extracellular alkalinity on both glutamate neurotoxicity and injury due to combined oxygen-glucose deprivation.

The effects of extracellular alkalinity during injury induced by exposure of murine neocortical cultures to glutamate (0.5 mM for 5 minutes) or oxygen-glucose deprivation are characterized morphologically and quantitated by efflux of lactate dehydrogenase from both neurons and glia to the bathing medium. Calcium accumulation is measured with calcium-45.

Moderate extracellular alkalinity is well tolerated by cortical cells but significantly potentiates both glutamate neuronal toxicity and oxygen-glucose deprivation neuronal injury. In contrast, glial viability in the face of combined oxygen-glucose deprivation is little affected by extracellular alkalinity. Increased accumulation of calcium-45 during oxygen-glucose deprivation in alkalotic medium and blockade of this increase by MK-801 is demonstrated.

These observations suggest that alkaline pH can exacerbate excitotoxic neuronal injury, most likely because of increased N-methyl-D-aspartate receptor activation. Metabolic alkalosis of any etiology may sensitize neurons to ischemic injury and potentiate reperfusion injury.
Lupus anticoagulant and anticardiolipin antibodies in young adults with cerebral ischemia.
Authors: Nencini P , Baruffi M C , Abbate R , Massai G , Amaducci L , Inzitari D
Published: June 2011

Our study evaluates in an unselected young population with cerebral ischemia the frequency of antiphospholipid antibodies; the relationship of antiphospholipid antibodies to conventional risk factors for and pathological mechanisms of cerebral ischemia; and the risk of recurrence of cerebral ischemia or systemic thrombotic events in patients with antiphospholipid antibodies compared with those without.

We prospectively tested for antiphospholipid antibodies in 55 of 59 young (aged 15-44 years) adults consecutively examined for ischemic stroke (n = 44) or transient ischemic attack (n = 11). These patients underwent a complete clinical and laboratory assessment for cerebral ischemia and had a 3-year mean follow-up.

Ten patients (18%), all with stroke, had antiphospholipid antibodies. Antiphospholipid antibodies were significantly more frequent in women than in men (Fisher's test, p = 0.014). Two patients with antiphospholipid antibodies had a new diagnosis of systemic lupus erythematosus. On angiography, none of the patients with antiphospholipid antibodies had extracranial lesions. Patients with antiphospholipid antibodies had significantly more prior cerebral events (Fisher's test, p = 0.014), and, by survival analysis, higher probability of cerebral ischemic or systemic thrombotic events during follow-up than patients without (log rank test, p less than 0.005).

We conclude that the prevalence of antiphospholipid antibodies is rather high in young adults with cerebral ischemia; that patients with cerebral ischemia and antiphospholipid antibodies may have unrecognized systemic lupus erythematosus; and that, among young patients with cerebral ischemia, patients with antiphospholipid antibodies constitute a subgroup at high risk of cerebral ischemic or systemic thrombotic recurrence. Prevention in this latter group may require close follow-up and treatment.
Efflux of glutamate produced by short ischemia of varied severity in rat striatum.
Authors: Ueda Y , Obrenovitch T P , Lok S Y , Sarna G S , Symon L
Published: June 2011

Evidence has accumulated suggesting that ischemia-induced neuronal damage may be linked to an extracellular overflow of glutamate. The purpose of this study was to provide new information about the time course of the increase in extracellular glutamate concentration associated with moderate and severe ischemia, and its relationship with electrical changes including anoxic depolarization.

Changes in the extracellular concentration of glutamate were continuously monitored in the rat striatum by microdialysis. Ischemia was induced by four-vessel occlusion for 3 or 5 minutes, and in some cases its severity was increased with a neck tourniquet. The severity of ischemia was assessed by electroencephalogram and direct current potential recording to detect anoxic depolarization.

In all experiments, the extracellular glutamate concentration began to increase shortly after the onset of ischemia and steadily rose throughout the ischemic period. Increases up to 35.0 mumol/l (2-3 mumol/l baseline; p less than 0.005) were observed when ischemia provoked the rapid occurrence of a large and sustained anoxic depolarization. Relatively smaller but still significant increases (6.9 mumol/l; p less than 0.005) were observed in penumbral conditions (electroencephalogram loss without anoxic depolarization). Glutamate began to be cleared immediately after reperfusion and 90% of released glutamate was cleared within 5 minutes, even when the preceding ischemia had been severe.

We propose that the extracellular glutamate concentration may not reach critical levels during short episodes of penumbral ischemia, but this might happen with a longer ischemic period.
Changes of neuronal transmission in the hippocampus after transient ischemia in spontaneously hypertensive rats and the protective effects of MK-801.
Authors: Suyama K
Published: June 2011

I studied the mechanism of postischemic neuronal degeneration in the hippocampus by an electrophysiological method.

Sequential changes of field potentials evoked by perforant path stimulation in the dentate gyrus and the CA1 region of the hippocampus were evaluated in spontaneously hypertensive rats up to 7 days after transient global ischemia induced by bilateral occlusion of the carotid arteries for 20 minutes after electrocauterization of the vertebral arteries. Animals were treated with vehicle or the excitotoxin antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10 amine (MK-801, 2 mg/kg or 5 mg/kg) intraperitoneally 30 minutes before ischemia.

Complete recovery of the population spike was observed in the dentate gyrus within 24 hours after recirculation, followed by a gradual reduction of population spike amplitude. In contrast, population spike in the CA1 region showed partial recovery 24 hours after recirculation, and an abrupt reduction of population spike amplitude occurred on day 2. There was no significant enhancement of population spike amplitude in either region throughout the experiment. Interneuronal recurrent inhibition in the dentate gyrus was enhanced on day 4, and ischemic changes were apparent in the CA1 pyramidal cells on day 7. Pretreatment with 5 mg/kg MK-801 prevented field potential and pathological changes completely in the dentate gyrus and partially in the CA1 region.

My results indicate that pathological changes of the CA1 pyramidal neurons after transient ischemia may not be the result of postischemic overstimulation. However, neuronal transmission in the CA1 region may be persistently impaired during or after transient ischemia.
A new model of temporary focal neocortical ischemia in the rat.
Authors: Buchan A M , Xue D , Slivka A
Published: June 2011

We describe a new rat model of temporary focal ischemia that produces neocortical ischemia without the need for prolonged anesthesia.

Temporary focal cerebral ischemia was initiated during halothane anesthesia, maintained for varying periods without anesthesia, and reversed by clip removal requiring brief anesthesia. Tandem carotid and middle cerebral artery occlusion for 1-4 hours and permanent occlusion were used to determine the duration and extent of ischemia necessary to produce predictable volumes of neocortical infarction in Wistar and spontaneously hypertensive rats.

In Wistar rats, occlusion of the right middle cerebral and both common carotid arteries resulted in cerebral blood flow reductions to approximately 8% of baseline. One hour of transient ischemia with 23 hours of reperfusion did not result in infarction. Three hours of ischemia followed by 21 hours of reperfusion resulted in infarction comparable to that caused by 24 hours of permanent ischemia. In spontaneously hypertensive rats, unilateral right middle cerebral and common carotid artery occlusion reduced cerebral blood flow to approximately 11% of baseline. Minimal damage was seen with 1 hour of reversible ischemia, but intervals of 2 and subsequently 3 hours followed by 22-21 hours of reperfusion produced progressively larger infarcts. Damage indistinguishable from that seen with 24 hours of permanent ischemia was seen with 3 or 4 hours of transient ischemia followed by 21 or 20 hours of reperfusion.

For unanesthetized normothermic rats, cerebral blood flow reductions to 10-20% of baseline resulted in maximal infarction once ischemic durations exceeded 2-3 hours. To be effective, experimental therapies aimed at lessening infarct size or restoring blood flow must be initiated within this critical time interval.
Dietary omega-3 fatty acids and endothelium-dependent responses in porcine cerebral arteries.
Authors: Kim P , Shimokawa H , Vanhoutte P M
Published: June 2011

We sought to determine the effect of dietary omega-3 polyunsaturated fatty acids on cerebrovascular endothelium-dependent responses in studies performed on isolated porcine basilar arteries.

Male Yorkshire pigs (6-8 weeks old) were kept for 4 weeks on a standard diet (control group, n = 12) or on chow supplemented with polyunsaturated fatty acids (eicosapentaenoic acid, 3.5 g/day, or docosahexaenoic acid, 1.5 g/day; treated group, n = 12). Isometric tension recording of the basilar artery was carried out and responses were compared between the two groups.

The regimen resulted in a decrease in the plasma arachidonic acid level and an increase in eicosapentaenoic acid. Endothelium-dependent relaxations induced by bradykinin and adenosine diphosphate were augmented in the basilar arteries of the treated group. Incubation with indomethacin (10(-5) M) prevented the augmentation of the relaxations induced by bradykinin, but not those caused by adenosine diphosphate. The indomethacin-sensitive, endothelium-dependent contractions to arachidonic acid remained comparable in the two groups, indicating that the activity of cyclooxygenase was not affected by the diet.

Dietary supplementation with omega-3 polyunsaturated fatty acids enhances endothelium-dependent relaxations in the basilar artery by two mechanisms: 1) replacement of endogenous arachidonic acid and suppression of the concomitant release of vasoconstrictor prostaglandins from the endothelium, and 2) enhancement of the release of endothelium-derived relaxing factor.