bluuebunny/crossref_metadata_2025 huggingface dataset:
Hippocampal unit activity after transient cerebral ischemia in rats.
Authors: Chang H S , Sasaki T , Kassell N F
Published: June 2011

Single unit activity of CA1 and CA3 neurons in the hippocampus was recorded in rats 1, 2, or 3 days after 10 minutes of transient cerebral ischemia induced by the clamping of both carotid arteries combined with hypotension. In addition, paired pulse inhibition/facilitation of the CA1 population spike was examined on Day 2 using two successive stimuli of the contralateral CA3 region delivered at various intervals. On Day 1, the mean +/- SEM firing rate in the CA1 region was 0.91 +/- 0.42/sec (n = 5), which was not significantly different from the control value of 0.98 +/- 0.26/sec (n = 5). Firing rate increased on Days 2 and 3 to 3.96 +/- 0.69/sec (n = 5), and 6.49 +/- 0.89/sec (n = 5), respectively. In the CA3 region, the mean +/- SEM firing rate of 1.18 +/- 0.27/sec in the five control rats sharply dropped to 0.14 +/- 0.11/sec in the five Day 1 rats and gradually increased to 0.45 +/- 0.11/sec in the five Day 3 rats. Histologic examination of these rats revealed ischemic changes restricted to CA1 neurons on Days 2 and 3. The paired-pulse experiment showed no significant difference between six control and six Day 2 rats in the inhibition of the second population spike with interstimulus intervals of less than 400 msec. At interstimulus intervals of greater than 500 msec there was facilitation of the second spike, which lasted 5 seconds in Day 2 rats. This facilitation was not observed in control rats. Because CA3 neurons constitute the main input to CA1 pyramidal cells, decreased activity of CA3 neurons indicates less excitatory input to CA1 neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Intravenously and iontophoretically administered naloxone reverses ischemic changes in rat hippocampus.
Authors: Dalkara T , Namer I J , Onur R , Zileli T
Published: June 2011

Forty rats under urethane anesthesia were subjected to cerebral ischemia by ligation of the right carotid, the right plus the left carotid, or the right carotid plus two vertebral arteries. Ischemia caused three types of changes in the field potential of the right hippocampal CA1 region evoked by fimbrial stimulation: 1) completely reversible deterioration (57% and 16% of the rats with unilateral and bilateral carotid artery ligation, respectively), 2) moderate deterioration (37% and 24% of the rats with unilateral and bilateral carotid artery ligation) and 3) irreversible loss of the evoked activity (6% and 60% of the rats with unilateral and bilateral carotid artery ligation and all the rats subjected to three-vessel occlusion). Naloxone improved the moderate deterioration in 10 of 11 rats (1-3 mg/kg i.v.) and in 15 of 16 (50-150 nA) iontophoretic applications, but naloxone did not restore the lost evoked activity. Intravenous morphine (10 mg/kg) aggravated the ischemic changes, and this effect was reversed by naloxone, while iontophoretic administration of morphine caused only excitation. These findings suggest that naloxone has a favorable effect on cerebral ischemia not severe enough to cause transmission failure. The reversal of ischemic changes by iontophoretic naloxone indicates that its site of action is at the neuronal or microcirculatory level.
Comparison of intraluminally versus extraluminally administered nimodipine on serotonin-induced cerebral vascular responses in vitro and in situ.
Authors: Vinall P E , Michele J J , Gordon D A , Simeone F A
Published: June 2011

The purpose of our study was to compare the ability of intraluminally and extraluminally administered nimodipine to inhibit serotonin-induced cerebral vascular responses in vitro and in situ. No difference was noted in the ability of nimodipine, whether administered intraluminally or extraluminally, to reduce the contractile response of extraluminally administered serotonin in a closed, pressurized, in vitro bovine middle cerebral artery preparation; histologic studies indicated that the tight endothelial junctions normally found in cerebral arteries remained intact in this preparation. In cats, pretreatment with nimodipine did not significantly reduce the ability of intracisternally injected serotonin to decrease cerebral blood flow; however, nimodipine did reduce the changes in cerebral artery diameter normally noted angiographically after serotonin injection. Although minor differences were noted between the intraluminal and extraluminal routes of administration of nimodipine in situ, in general the effects were comparable.
Enhanced erythrocyte aggregability in occlusive cerebrovascular disease.
Authors: Tanahashi N , Gotoh F , Tomita M , Shinohara T , Terayama Y , Mihara B , Ohta K , Nara M
Published: June 2011

We measured the rate of erythrocyte aggregation using our whole-blood aggregometer in 80 patients with occlusive cerebrovascular disease during the acute and chronic phases. We compared the data with values for 38 age-matched healthy controls. Mean +/- SD erythrocyte aggregability of the patients during both the acute phase (0.145 +/- 0.21/sec, n = 35) and the chronic phase (0.139 +/- 0.21/sec, n = 45) was higher than that in the controls (0.123 +/- 0.21/sec, n = 38; p less than 0.01). Erythrocyte aggregability was positively correlated with the plasma concentration of globulin and fibrinogen and inversely correlated with the albumin:globulin ratio. However, these correlations did not necessarily exclude the possibility that some unknown substance(s) released from ischemic tissue might enhance erythrocyte aggregability.
Hypoxia-induced increases in hypoxic tolerance augmented by beta-hydroxybutyrate in mice.
Authors: Rising C L , D'Alecy L G
Published: June 2011

A standard murine model was used to determine whether acute pretreatment exposures to hypoxia could alter ultimate hypoxic survival time. Adult male albino mice (Mus musculus) weighing 25-30 g were subjected to three pretreatment hypoxic exposures (4.5% O2, balance N2) of increasing duration (90, 120, and 150 seconds) with 300 seconds of normoxia between each pretreatment exposure and before testing of hypoxic survival time. Acute pretreatment exposures to hypoxia significantly increased mean +/- SEM hypoxic survival time from 108 +/- 4 to 403 +/- 42 seconds. Mean +/- SEM blood glucose concentrations increased significantly from 201 +/- 19 to 397 +/- 10 mg/dl immediately after hypoxic pretreatment. A significant increase in mean +/- SEM blood ketone concentrations, from 0.15 +/- 0.01 to 0.40 +/- 0.08 mM, was detected in the blood 1,800 seconds but not 300 seconds after hypoxic pretreatment. However, pretreatment with exogenous glucose or ketones alone, to mimic the blood levels seen after hypoxic pretreatment, failed to increase hypoxic survival time. In contrast, mice pretreated with hypoxic exposures plus the exogenous substrate beta-hydroxybutyrate had an increased mean +/- SEM hypoxic survival time of 749 +/- 48 seconds and a decreased body temperature. Stepwise Cox regression analyses with body temperature as a fixed covariate suggest that this decrease in body temperature has a partial role in, but can not fully account for, the increased hypoxic survival time. These data suggest that sequential exposures to hypoxia induce metabolic changes that protect against the lethal effects of hypoxia, perhaps by altering substrate mobilization and utilization and/or by inducing a hypometabolic hypothermia.
Modification of acute focal ischemia in rabbits by poloxamer 188.
Authors: Colbassani H J , Barrow D L , Sweeney K M , Bakay R A , Check I J , Hunter R L
Published: June 2011

We studied the effect of a synthetic copolymer surfactant, poloxamer 188, on cerebral blood flow in a rabbit model of focal cerebral ischemia. Following retro-orbital craniectomy, the parietal branch of the middle cerebral artery was occluded with bipolar current. Cerebral blood flow was measured by the hydrogen clearance technique using platinum-iridium electrodes placed within the parietal cortex. Ten rabbits were infused with 50 mg/kg poloxamer 188 in saline beginning 30 minutes after occlusion; 12 control rabbits received an equal volume of saline. Poloxamer 188 increased blood flow significantly in areas of severe or moderate ischemia but had little effect in areas with mild or no ischemia. The improvement in blood flow could not be accounted for by hemodilution, and the copolymer did not affect blood viscosity at any shear rate from 1 to 100 sec-1. We hypothesize that poloxamer 188 increases circulation in ischemic tissue by inhibiting adhesive interactions among proteins (fibrin and fibrinogen) and cells in the microcirculation.
Continuous lidocaine infusion and focal feline cerebral ischemia.
Authors: Shokunbi M T , Gelb A W , Wu X M , Miller D J
Published: June 2011

We measured somatosensory evoked potentials, infarct size, and cerebral blood flow in 20 cats subjected to occlusion of the middle cerebral artery for 3 hours, followed by an equal period of reperfusion. The cats were randomized into a treatment group that received a continuous infusion of 2 mg/kg lidocaine hydrochloride or a control group that received an equivalent volume of normal saline. All 10 treated cats retained measurable evoked potentials throughout the experiment. In five control cats, evoked potentials disappeared completely at some point during the occlusion (difference between groups significant at p less than 0.001). Mean amplitude of the major cortical wave in the nine treated cats with cerebral infarcts was higher than that of the nine corresponding controls (p less than 0.05). Lidocaine reduced the mean +/- SEM size of the infarcts from 30.1 +/- 6.0% in the control group to 14.7 +/- 4.9% in the treated group (p less than 0.05). As blood flow was reduced in the infarct and peri-infarct zones in the control but not the treated cats, our results suggest that the beneficial effects of lidocaine may be due to preservation of blood flow in the ischemic zone.
Prolonged hypoperfusion and early stroke after transient ischemic attack.
Authors: Bogousslavsky J , Delaloye-Bischof A , Regli F , Delaloye B
Published: June 2011

Many patients suffer a stroke early after a transient ischemic attack, but the reason why is often unclear. We studied 12 patients with less than 75% stenosis of the internal carotid artery and a single hemispheric transient ischemic attack lasting less than 1 hour who had a normal neurologic examination 3-13 hours later and a normal computed tomogram 24-36 hours later. Single-photon emission computed tomography using technetium-99m HM-PAO less than or equal to 50 hours after the attack showed no abnormality in eight patients, but in the other four there was an area with 30-50% reduction in perfusion ipsilateral to the transient ischemic attack. Three of these four patients developed an ipsilateral infarct 3-7 days later, but none of the eight patients with normal single-photon emission computed tomograms had a stroke during the following weeks. No difference in therapy, risk factors, severity of internal carotid artery disease, or timing of the technetium-99m study could explain these findings. We suggest that some transient ischemic attacks, though clinically identical to others, may be associated with persisting focal hypoperfusion, which predisposes to early stroke.
The effect of gas emboli on rabbit cerebral blood flow.
Authors: Helps S C , Parsons D W , Reilly P L , Gorman D F
Published: June 2011

Many bubbles that enter the brain circulation pass through the arterioles and capillary beds and do not obstruct blood flow. Nevertheless, such bubbles could still disrupt brain function. An open-brain model in five anesthetized rabbits used the minimum dose of air (25 microliters) necessary to cause embolism of the exposed vessels, and these bubbles passed through the vessels without any trapping. Despite their rapid transit, the bubbles provoked a marked dilatation of the affected pial arterioles (mean increase after 15 minutes of 27%) that persisted for 90 minutes after the bubbles had disappeared. The changes in vessel diameter were associated with a delayed, but significant and progressive, reduction in both cerebral blood flow measured by hydrogen clearance and neural function measured by cortical somatosensory evoked response. The decrease in blood flow correlated well with the depression of neural function (r = 0.67). Because both cerebral blood flow and neural function temporarily returned to normal after air embolism, the subsequent changes seen in this model cannot be explained simply by the mechanical obstruction of blood flow by bubbles.
Hemodynamics in internal carotid artery occlusion examined by positron emission tomography.
Authors: Yamauchi H , Fukuyama H , Kimura J , Konishi J , Kameyama M
Published: June 2011

Using positron emission tomography in nine patients with minor strokes, unilateral internal carotid artery occlusion, and good collateral circulation through the anterior portion of the circle of Willis, we analyzed regional cerebral blood flow, cerebral metabolic rate of oxygen, oxygen extraction fraction, and cerebral blood volume. These studies allowed quantification of the regional hemodynamic status, especially in relation to watershed areas. Compared with eight normal controls, the patients had significantly (p less than 0.01) decreased regional cerebral blood flow in the middle cerebral artery territory and the surrounding watershed areas of the occluded hemisphere. The oxygen extraction fraction rose with the distance from the anterior portion of the circle of Willis, attaining the highest value in the superior parietal and posterior temporo-occipital watershed area. A concomitant decrease in the cerebral blood flow/cerebral blood volume ratio suggested reduction in the mean blood flow velocity, whereby elevated blood viscosity would be more liable to reduce cerebral blood flow. These findings suggest hemodynamic vulnerability of the watershed areas after internal carotid artery occlusion in persons with good collateral circulation through the anterior portion of the circle of Willis. Our results also emphasize the importance of systemic hemodynamic factors such as blood pressure and circulating blood volume in the genesis of watershed infarction.
Leukoaraiosis, intracerebral hemorrhage, and arterial hypertension.
Authors: Inzitari D , Giordano G P , Ancona A L , Pracucci G , Mascalchi M , Amaducci L
Published: June 2011

To investigate whether the observed association of leukoaraiosis with intracerebral hemorrhage is direct or mediated by risk factors, we compared 116 patients with intracerebral hemorrhage confirmed by computed tomography and 155 controls without intracerebral hemorrhage, evaluating the prevalence of leukoaraiosis and vascular risk factors. Leukoaraiosis was observed in 21 (18%) of the 116 patients and in 12 (8%) of the 155 controls (p less than 0.01). Only two (6%) of the 31 patients with lobar hemorrhage had leukoaraiosis on computed tomograms, compared with 17 (24%) of the 71 patients with basal ganglionic hemorrhage (p less than 0.05). Leukoaraiosis was significantly correlated with intracerebral hemorrhage after controlling for age and sex by using multiple logistic regression analysis, while the correlation disappeared after controlling for hypertension. Our results indicate that leukoaraiosis is not an independent risk factor for intracerebral hemorrhage.
Evidence for platelet-activating factor as a novel mediator in experimental stroke in rabbits.
Authors: Lindsberg P J , Yue T L , Frerichs K U , Hallenbeck J M , Feuerstein G
Published: June 2011

Platelet-activating factor is a potent mediator of inflammation, which has untoward effects on cerebrovascular and neural elements. While several investigators have reported attenuation of ischemic damage after treatment with antagonists of platelet-activating factor, no study has proved endogenous production of platelet-activating factor in ischemia of the central nervous system. We hypothesized that endogenous production of platelet-activating factor participates in the early pathologic manifestations of deteriorating stroke. In 12 rabbits, we found tissue levels of platelet-activating factor measured by the release of serotonin from washed platelets to be elevated by approximately 20-fold in spinal cord injured by 25 minutes of ischemia and 2 hours of reperfusion (2.80 +/- 0.98 ng/g) compared with that in normal spinal cord (0.15 +/- 0.06 ng/g, p less than 0.01). Given during ischemia to seven rabbits, 10 mg/kg i.p. of a highly selective and potent antagonist of platelet-activating factor (BN 50739) accentuated the early postischemic hyperemia and prevented the delayed hypoperfusion measured by on-line laser-Doppler flowmetry (-35 +/- 7% of baseline [n = 7] without versus 33 +/- 14% with treatment, p less than 0.01) and the edema formation measured as the increase in tissue water content (4.4 +/- 0.7% without [n = 6] versus 2.1 +/- 0.6% with [n = 7]treatment, p less than 0.05) after 2 hours of reperfusion. This neurochemical and pharmacologic evidence emphasizes a new perspective of ischemia-induced phospholipid degradation and suggests an important role for platelet-activating factor in the early manifestations of stroke.
Pharmacologic irreversible narrowing in chronic cerebrovasospasm in rabbits is associated with functional damage.
Authors: Vorkapic P , Bevan R D , Bevan J A
Published: June 2011

We studied isolated basilar artery segments from a rabbit model of chronic cerebrovasospasm. Autologous blood placed around the basilar artery of rabbits killed 1, 2, 3, 4, 5, 6, 7, or 9 days later caused narrowing of the segments with a biphasic time course. The first (immediate) phase was reversed by intra-arterial papaverine; the second phase exhibited an increasing component of narrowing that was papaverine-insensitive. Based on the passive force/length curves, basilar artery segments became increasingly stiff over 9 days. By contrast, the segments' contractility decreased. Responses of the basilar artery segments were greater over the first few days, but then became less than that of saline-injected controls. Contractions in response to norepinephrine and potassium were reduced. Endothelium-based acetylcholine-induced vasodilation progressively diminished, as did the response to sympathetic nerve stimulation. There was a negative correlation between artery wall stiffness and contractility. The papaverine-insensitive component of angiographic narrowing correlated directly with loss of contractility and with artery wall stiffness. These results are consistent with the conclusion that increased artery wall stiffness is a primary determining factor in the arterial narrowing of chronic cerebrovasospasm.
Therapeutic window of CA1 neuronal damage defined by an ultrashort-acting barbiturate after brain ischemia in gerbils.
Authors: Kuroiwa T , Bonnekoh P , Hossmann K A
Published: June 2011

Previous therapeutic studies on the prevention of selective vulnerability of neurons in the hippocampus have suggested that the critical period for induction of delayed neuronal injury occurs early during recirculation. To determine the onset and duration of this period, an ultrashort-acting barbiturate (methohexital) was infused into the left carotid artery of 47 gerbils after various times of recirculation following 10 minutes of bilateral forebrain ischemia. Neuronal density in the left CA1 sector was determined 7 days later by counting the number of surviving neurons per millimeter of pyramidal cell layer. In 16 saline-treated gerbils, less than 10% of the CA1 neurons survived the 10 minutes of ischemia. Postischemic carotid infusion of methohexital improved neuronal survival, the degree of improvement depending on the timing and duration of the methohexital infusion. When carried out during the initial 40 minutes of recirculation, methohexital infusion for 10 minutes increased the number of surviving neurons to approximately 60% of that in five sham-operated control gerbils. This increase was significant for infusions carried out between the 10th and 20th minutes (n = 6, p less than 0.05) and between the 30th and 40th minutes (n = 6, p less than 0.05) of recirculation. Methohexital infusion for 20 minutes increased neuronal survival to 95% and 73% of that in the controls when carried out between the 0th and 20th minutes (n = 5, p less than 0.005) and between the 20th and 40th minutes (n = 5, p less than 0.005) of recirculation, respectively. Protection was nonsignificant for 10- or 20-minute methohexital infusions carried out after the 40th minute of recirculation. Our results demonstrate that the pathologic processes leading to delayed neuronal injury in the CA1 sector are induced during the initial 40 minutes of recirculation and that barbiturates are able to reverse these processes only if given during this period.
Two cases of spontaneous internal carotid artery occlusion due to giant intracranial carotid artery aneurysm.
Authors: Sato K , Fujiwara S , Yoshimoto T , Onuma T
Published: June 2011

Although spontaneous thrombosis of a giant intracranial aneurysm is relatively common, occlusion of its parent artery is rare. We describe two recent patients in whom the parent artery spontaneously occluded. One patient had severe stenosis of the left internal carotid artery, with delayed appearance of a faint shadow of vascular widening near the posterior clinoid process. One month later, complete occlusion of the left internal carotid artery was shown angiographically. The second patient had dysarthria and left hemiparesis, resulting in the diagnosis of a left internal carotid artery giant aneurysm. He had suffered an episode of visual disturbance of the right eye 5 years before. Angiography showed the right cervical internal carotid artery to be occluded. We believe the mechanism of parent artery occlusion in our two patients to be due first to stretching of the internal carotid artery by the enlarged aneurysm, followed by compression of the internal carotid artery by the aneurysm itself. Next, the anterior clinoid process and the optic nerve are involved, and, finally, thrombosis of the aneurysmal cavity extends into the internal carotid artery itself.
Effect of emitted power on waveform intensity in transcranial Doppler.
Authors: Halsey J H
Published: June 2011

This study assesses the problem of transcranial Doppler recording failure and seeks to determine the extent to which this can be ameliorated by increased emitted power. We hypothesized that waveform intensity is directly related to the rate and quality of successful recording and may be compared quantitatively among groups of patients. Among a large group of patients recorded at 800 mW/cm2 emitted power, intensity was strongest in white men, weakest in black women, and intermediate in black men and white women. It declined with age in women of either race, but not in men of either race. Analysis of the effect of emitted power on intensity predicted that significant numbers of waveforms recorded at 800 mW/cm2 could not be recorded at the current clinical standards of 100 mW/cm2, the difference being most pronounced in elderly black women. Temporal bone window thickness measured in a series of adult cadaver skulls was least in white men, greatest in black women, and intermediate in black men and white women. The findings of this study support the hypothesis that temporal bone window thickness is an important determinant of recording difficulty and suggest that increased emitted power can significantly increase successful recording, particularly in black and elderly patients. Increased power alone, however, cannot completely solve the recording problem within safe limits.
Correlates of middle cerebral artery blood velocity in the elderly.
Authors: Ameriso S F , Paganini-Hill A , Meiselman H J , Fisher M
Published: June 2011

We analyzed the association between hematologic factors and blood velocity of the middle cerebral artery in 42 healthy ambulatory subjects aged 63-86 years. We found a significant inverse association between mean velocity and both hematocrit (r = -0.37, p less than 0.02) and fibrinogen concentration (r = -0.42, p less than 0.005). These two variables are independently associated with velocity and together explain 29% of the variance in mean velocity. Both hematocrit and fibrinogen concentration should be considered in the interpretation of transcranial Doppler findings in this population.
Leukotriene constriction of mouse pial arterioles in vivo is endothelium-dependent and receptor-mediated.
Authors: Rosenblum W I , Nelson G H , Nishimura H
Published: June 2011

The diameters of pial arterioles of mice were monitored in vivo with an image-splitting technique and television microscopy. Concentrations of leukotriene C4 as low as 10(-7) M constricted the arterioles. The leukotriene C4-D4 receptor blocker ICI 198615 (10(-8) M) inhibited the response. Endothelial injury by helium-neon laser/Evans blue technique eliminated the constriction and unmasked a slight but consistent relaxation that was not inhibited by 10(-8) M ICI 198615. Since leukotrienes are produced by the brain and enter the cerebrospinal fluid in ischemia, head trauma, and subarachnoid hemorrhage, the possibility that leukotrienes C4 and D4 contribute to decreases in cerebral blood flow during these conditions should be considered. However, the present data makes such a possibility far less likely because the endothelium is frequently injured in these conditions, and therefore the ability of leukotrienes to constrict vessels would be severely curtailed.
Transcranial color-coded real-time sonography in adults.
Authors: Bogdahn U , Becker G , Winkler J , Greiner K , Perez J , Meurers B
Published: June 2011

We investigated the diagnostic potential of transcranial color-coded real-time sonography in 52 individuals using a phased-array ultrasound system with color-coded blood flow representation. Ultrasound scans in the axial and coronal planes were feasible through temporal acoustic bone windows in 49 subjects, enabling depiction of the main parenchymal and vascular structures as well as the ventricular system. Color-coded representation of blood flow in the cerebral vessels allowed unequivocal identification of the circle of Willis within the anatomic black-and-white B-mode image of the parenchymal structures. In Doppler mode, vascular blood flow phenomena may be analyzed semiquantitatively using the Doppler frequency spectrum. This noninvasive, serially applicable, mobile beside method may complement conventional neuroradiologic imaging methods, allowing on-line studies of functional processes within the adult brain.
Endothelium-independent contractions of human cerebral arteries in response to vasopressin.
Authors: Martín de Aguilera E , Vila J M , Irurzun A , Martínez M C , Martínez Cuesta M A , Lluch S
Published: June 2011

We studied the effects of vasopressin in isolated segments from branches (500-700 micrograms in external diameter) of human middle cerebral arteries obtained during autopsy of 15 patients who had died 3-8 hours before. Paired segments, one normal and the other de-endothelized by gentle rubbing, were mounted for isometric recording of tension in organ baths. In 11 normal segments, vasopressin produced concentration-dependent contractions with an EC50 of 7.0 X 10(-10) M. Removal of the endothelium from 12 segments did not significantly affect vasopressin-induced contractions. Vasopressin produced further contractions in arterial segments with (n = 4) or without (n = 5) endothelium precontracted with KCl. In segments precontracted with prostaglandin F2 alpha, acetylcholine choline caused relaxation only of those with endothelium. At 10(-8) M (n = 11), the vasopressin V-1 receptor antagonist d(CH2)5Tyr(Me)AVP produced a 60-fold shift to the right of the control response curve for vasopressin. Increasing the concentration of the receptor antagonist to 10(-6) M (n = 7) further displaced the control curve in a parallel manner. These results indicate that vasopressin exerts a powerful constrictor action on isolated human cerebral arteries by direct stimulation of V-1 receptors located predominantly on smooth muscle cells. It appears that this contractile response is not modulated by the presence of an intact endothelial cell layer.
Cerebral blood flow and oxygen metabolism in patients with vascular dementia of the Binswanger type.
Authors: Yao H , Sadoshima S , Kuwabara Y , Ichiya Y , Fujishima M
Published: June 2011

We performed clinical and neuroradiologic studies, including positron emission tomography, in five patients with vascular dementia of the Binswanger type. The clinical features of these cases consisted of slowly progressive dementia, together with vascular risk factors such as hypertension and often a history of minor stroke, and characteristic white matter lesions on brain computed tomograms or magnetic resonance images. Digital subtraction angiography of the cervical and intracranial arteries demonstrated no occlusive lesion in any patient. Both cerebral blood flow and the cerebral metabolic rate for oxygen were markedly reduced in the white matter (54-77% of control values), and both were decreased in the parietal (73% of control), frontal (74-80%), and temporal (74-83%) cortices, where no abnormalities were detected by brain computed tomography or magnetic resonance imaging. We conclude that vascular dementia of the Binswanger type may be caused by disconnection between the cerebral cortex and subcortical structures due to ischemic damage in the white matter.
Tissue plasminogen activator reduces brain injury in a rabbit model of thromboembolic stroke.
Authors: Bednar M M , McAuliffe T , Raymond S , Gross C E
Published: June 2011

Tissue plasminogen activator is an endogenous fibrin-specific serine protease with potent thrombolytic activity. We investigated the efficacy of tissue plasminogen activator in reducing cerebral infarct size after thromboembolic stroke in a rabbit model. Seventeen rabbits were randomized to receive either tissue plasminogen activator (2.5 mg/kg, n = 6) or vehicle control (n = 11). We controlled mean arterial pressure, hematocrit, and arterial blood gases before and after the intracarotid embolization of an autologous clot. Cerebral blood flow (cm3/100 g/min) (mean +/- SEM) was immediately reduced from 55.2 +/- 7.7 to 8.5 +/- 2.5 in the control group and from 61.8 +/- 14.8 to 10.0 +/- 3.5 in the treated group after embolization. Cerebral blood flow recovered significantly within 60 minutes of thrombolytic therapy and attained a value of 59.6 +/- 10.0 cm3/100 g/min 4 hours after embolization, whereas cerebral blood flow in control animals demonstrated only a minimal recovery to 15.3 +/- 8.9 cm3/100 g/min. Cerebral infarct size (percent of hemisphere) was reduced from 34.4 +/- 5.6% in control animals to 8.8 +/- 5.6% in treated animals (mean +/- SEM, p less than 0.01). These results suggest that tissue plasminogen activator may be efficacious in restoring cerebral blood flow and thus limiting infarct size in acute thromboembolic stroke.
Correlation between amino acid release and neuropathologic outcome in rat brain following middle cerebral artery occlusion.
Authors: Butcher S P , Bullock R , Graham D I , McCulloch J
Published: June 2011

Using in vivo brain microdialysis, we studied amino acid release in the striatum and cortex of eight rats following permanent middle cerebral artery occlusion. We then processed all brains for histopathologic assessment of the volume of ischemic damage 4 hours after occlusion. Ischemic damage was varied by occlusion of the middle cerebral artery at a point either proximal (n = 4) or distal (n = 4) to the lenticulostriate vessels. Proximal occlusion elevated the dialysate contents of all amino acids. The largest increases occurred for the potentially neurotoxic amino acids aspartate and glutamate and for taurine (800-2,800% of basal efflux). We observed smaller increases for the "metabolic" amino acids (280-580% of basal efflux). Distal occlusion did not affect amino acid efflux in the striatum, and release in the cortex was significantly lower than that following proximal occlusion. We compared release data with acute histopathologic outcome. Proximal occlusion resulted in a large volume of ischemic damage in the cortex and striatum (25-48% of hemispheric volume). A smaller volume of ischemic damage was noted following distal occlusion (0-21% of hemispheric volume). The volume of ischemic damage and the amount of amino acid release were significantly correlated (p less than 0.05).
Risk factors for stroke in middle-aged men in Göteborg, Sweden.
Authors: Harmsen P , Rosengren A , Tsipogianni A , Wilhelmsen L
Published: June 2011

To evaluate stroke risk factors in Göteborg, Sweden, during 1970-1973 a cohort of 7,495 participating men from a general population sample of 9,998 men aged 47-55 years were examined with respect to cardiovascular risk factors. Men with hypertension and hypercholesterolemia and men who were heavy smokers were treated. We assessed stroke end points and cause-specific mortality using a stroke register and death certificates. During a mean follow-up of 11.8 years, 230 strokes occurred in the entire population sample (participants and nonparticipants) (7% subarachnoid hemorrhages, 13% intracerebral hemorrhages, 42% cerebral infarctions, and 38% unspecified strokes). Using univariate analysis, we found measured high blood pressure (systolic and diastolic), smoking, known hypertension, diabetes mellitus, stroke in either parent, severe psychological stress, marital status, atrial fibrillation, previous transient ischemic attacks, previous myocardial infarction, effort-induced chest pain, and intermittent claudication to be significantly related to all stroke. Of the stroke types, subarachnoid hemorrhage was not related to any of these indicators, and intracerebral hemorrhage was related only to measured high blood pressure. Using multivariate analyses, we found measured high blood pressure, smoking, and severe psychological stress as well as atrial fibrillation, previous transient ischemic attacks, and intermittent claudication to be independent risk factors for nonhemorrhagic stroke. Serum cholesterol concentration, occupational and leisure-time physical activity, body mass index, alcohol abuse, and low occupational class were not risk factors for stroke.
A single-photon emission computed tomography study of hypoperfusion after subarachnoid hemorrhage.
Authors: Davis S , Andrews J , Lichtenstein M , Kaye A , Tress B , Rossiter S , Salehi N , Binns D
Published: June 2011

We used single-photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime in 18 studies on 13 patients with subarachnoid hemorrhage to determine whether any changes in cerebral blood flow could be correlated with clinical or computed tomographic evidence of delayed ischemia. Among the seven patients without focal neurologic deficits, regional cerebral hypoperfusion was demonstrated in only one who died. Among the 10 patients with aneurysmal subarachnoid hemorrhage, one died before surgery, and six developed postoperative delayed ischemic deficits, of whom two died. Among the patients with angiographically documented aneurysms, regional hypoperfusion correlated with the presence and severity of delayed neurologic deficits, whereas correlative computed tomographic scans showed either early infarction or no relevant abnormality. This technique facilitates early diagnosis of cerebral tissue hypoperfusion due to vasospasm after subarachnoid hemorrhage.
Three-minute blood flow index for assessment of cerebrovascular reserve.
Authors: Young W L , Prohovnik I , Correll J W , Ostapkovich N
Published: June 2011

Regional cerebral blood flow studies with xenon-133 are useful in the functional assessment of cerebrovascular diseases. Conventional models for cerebral blood flow calculation employ 11 minutes of data collection. However, in many circumstances it is not possible to maintain steady-state physiologic conditions for 11 minutes. We compared a monocompartmental model that requires only 3 minutes of data collection with the bicompartmental model that requires 11 minutes of data collection. The correlation between the absolute values for global cerebral blood flow (initial slope index, intravenous method) in 72 anesthetized patients was r = 0.88; for 54 awake patients inhaling xenon-133, the correlation was r = 0.77. Cerebral blood flow was determined with intravenous xenon-133 at baseline and during a CO2 challenge in 50 patients during cerebrovascular surgery under general anesthesia. Reactivity to a 10-mm Hg rise in PaCO2 was calculated in absolute terms and as a percentage change from baseline using both the 3-minute and the 11-minute models. The correlation of CO2 reactivity calculated with the two models was r = 0.9 for the absolute values and r = 0.8 for the relative change. Cerebral blood flow calculated with the two models correlated well in both awake and anesthetized patients. In addition, there was a good correlation between CO2 reactivity calculated with the two models. In situations in which physiologic conditions cannot be held stable for 11 minutes, the 3-minute initial slope index may be used to quantitatively assess cerebrovascular reserve with a CO2 challenge.
Prospective study of anticardiolipin antibodies in stroke.
Authors: Kushner M J
Published: June 2011

Over 2 years, 104 patients underwent clinical evaluation and laboratory screening for the presence of abnormal anticardiolipin antibodies to determine the profile of laboratory and clinical findings in patients with stroke and other neurologic disorders. Seven with incomplete or ambiguous data were excluded; of the remaining 97 patients, 31 were greater than or equal to 65 years old. Nine patients suffered systemic lupus erythematosus, 45 suffered brain ischemia, and 43 suffered other nonischemic neurologic disorders. Cardiac arrhythmia, myocardial infarction, and cardiac valvulopathy were grounds for exclusion. The presence of anticardiolipin antibodies was not influenced by age. In the 88 patients without lupus, anticardiolipin antibodies were significantly more common in the group suffering brain ischemia than in the group with nonischemic neurologic disorders (29% versus 5%, p less than 0.01, chi 2 test). These controlled data demonstrate an association between the presence of circulating anticardiolipin antibodies with stroke, but not with other neurologic conditions.
Methionine sulfoximine reduces cortical infarct size in rats after middle cerebral artery occlusion.
Authors: Swanson R A , Shiraishi K , Morton M T , Sharp F R
Published: June 2011

The methionine analogue methionine sulfoximine was administered to 10 rats 24 hours before occlusion of the proximal left middle cerebral artery. Three days later the rats were decapitated and the brain infarct volumes were compared with those in 10 control rats that received saline before middle cerebral artery occlusion. The mean volume of the infarct in the cerebral cortex was reduced by 33% in the group treated with methionine sulfoximine (p less than 0.01). This protective effect may be mediated by a presynaptic mechanism; methionine sulfoximine profoundly inhibits brain glutamine synthetase, thereby interrupting the astrocyte-neuron glutamate shuttle and impairing neuronal glutamate release. Methionine sulfoximine also increases brain glycogen stores, and this increased energy reserve may benefit penumbral tissue during the peri-infarct period. Further study of the mechanisms by which methionine sulfoximine decreases infarct volume could lead to new therapeutic approaches for stroke.
Detection of middle cerebral artery emboli during carotid endarterectomy using transcranial Doppler ultrasonography.
Authors: Spencer M P , Thomas G I , Nicholls S C , Sauvage L R
Published: June 2011

The purpose of our study was to define the signal characteristics and clinical circumstances associated with emboli detected in the middle cerebral artery using 2-MHz pulsed transcranial Doppler ultrasound in patients undergoing carotid endarterectomy. Signals designating emboli were transients displaying harmonic qualities the signatures of which were clearly different from those of mechanical and electronic artifacts. We reviewed the audio/video tape recordings from 91 patients for signals of air bubble emboli occurring upon release of common carotid artery crossclamps; recordings from 35 patients (38%) demonstrated air bubble emboli. Transients with signatures identical to those of air bubble emboli were also discovered when bubbles in the bloodstream were improbable; we defined these transients as representing formed-element emboli. Such signals were found in recordings from 24 patients (26%), and they occurred before (both spontaneously and upon common carotid artery compression), during, and after surgical dissection. Signals indicating formed-element emboli were associated with intraluminal platelet thrombus, with ulcerations in the carotid artery, and with transient ischemic attacks or stroke. Most postoperative formed-element emboli did not cause symptoms but, when persisting for hours, they were associated with strokes and cerebral infarction. This Doppler ultrasound method of detecting emboli will be useful in the study of stroke mechanisms and as a clinical test to guide the medical and surgical treatment of patients at risk of stroke.
Neurologic complications of late prosthetic valve endocarditis.
Authors: Keyser D L , Biller J , Coffman T T , Adams H P
Published: June 2011

We reviewed the records of 20 patients with late prosthetic valve endocarditis who were hospitalized at the University of Iowa between 1985 and 1988. There were 14 men and six women, aged 20-80 (mean 57.9) years. The infected valves were mechanical in 11 patients (six aortic and five mitral) and bioprosthetic in the other nine. Echocardiography in 12 patients demonstrated vegetations in one. Among the 20 patients, neurologic complications occurred in eight (40%), six of whom had mechanical valves (five mitral and one aortic). Infection with Staphylococcus aureus occurred in four of the eight patients (50%) with neurologic complications. Of the eight patients with neurologic complications, ischemic stroke was diagnosed in four, transient ischemic attacks in one, and intracranial hemorrhage in three. Prothrombin times at the time of the intracranial hemorrhage were 2.2, 1.5, and 1.3 times control in these three patients. Cerebral angiography done in four of the eight patients with neurologic complications failed to show mycotic aneurysms. Nine of the 20 patients (seven men and two women, mean age 66.8 years) died less than or equal to 90 days after the diagnosis of late prosthetic valve endocarditis. Half of the eight patients with neurologic complications died (three men and one woman, mean age 62.3 years), and all three patients with intracranial hemorrhage died. Our data suggest that the neurologic complications of late prosthetic valve endocarditis are more common with mechanical valves, particularly in the mitral position, and are associated with a high mortality.
Carotid transient ischemic attacks and normal investigations: a follow-up study.
Authors: Shuaib A , Hachinski V C
Published: June 2011

Reports on the long-term prognosis of patients with transient ischemic attacks and normal angiograms have revealed variable results, some suggesting a good prognosis while others report an outcome no different from that of patients with transient ischemic attacks and atherosclerotic vascular narrowing. Normal cerebral angiograms do not exclude disease in the heart or hematologic disorders. The prognosis for patients with transient ischemic attacks, normal angiograms, and normal results of cardiac and hematologic investigations is not known. We report our experience with 43 patients (26 men and 17 women, mean age 55.6 years) with transient ischemic attacks and normal findings on all investigations (including angiography, cranial computed tomography, echocardiography, and Holter monitoring). The patients were followed for a mean of 4.43 years. Six patients had recurrent transient ischemic attacks and six developed angina pectoris. No patient developed a stroke. In the presence of normal cerebral, cardiac, and hematologic findings, the long-term prognosis of patients with transient ischemic attacks is good. However, the development of cardiac disease during follow-up could not be predicted using the available diagnostic methods.
Transesophageal echocardiography in the detection of intracardiac embolic sources in patients with transient ischemic attacks.
Authors: Pop G , Sutherland G R , Koudstaal P J , Sit T W , de Jong G , Roelandt J R
Published: June 2011

Using both precordial and transesophageal echocardiography, we studied 72 consecutive patients with a recent unequivocal transient ischemic attack or nondisabling stroke to determine the relative value of the two techniques for detecting potential intracardiac sources of cerebral emboli. Group 1 (n = 53) patients had no clinical cardiac abnormality, and group 2 (n = 19) patients had abnormal cardiac findings upon clinical examination. In group 1, precordial echocardiography detected an abnormality in only one patient (aortic valve thickening) but transesophageal echocardiography defined morphologic abnormalities in five patients (one with a left atrial appendage mass lesion, one with aortic dissection, one with mitral valve prolapse, one with a mitral leaflet mass lesion, and one with aortic valve thickening). In group 2, both precordial and transesophageal echocardiographic studies were normal in 13 patients, while both were abnormal in the remaining six patients. Five of these six patients had pathologic left atrial and/or left ventricular dilatation, but only transesophageal echocardiography defined a left atrial appendage thrombus in two of the six. The sixth patient had mitral chordal rupture, seen on both precordial and transesophageal echocardiography. In addition, in 32 of the 72 patients transesophageal echocardiography identified widespread thoracic aortic atherosclerotic plaques not visualized by precordial echocardiography. We conclude that transesophageal echocardiography significantly increases the yield in visualizing potential intracardiac sources of emboli compared with precordial echocardiography. However, the precise clinical value of the former in the management of such patients requires further study as the number of abnormal transesophageal echocardiographic findings is not high and a causative relation with transient ischemic attacks cannot be proven.
Prevention of ischemic-hypoxic brain injury and death in rabbits with fructose-1,6-diphosphate.
Authors: Farias L A , Smith E E , Markov A K
Published: June 2011

Fructose-1,6-diphosphate has been shown to improve neurologic recovery following resuscitation from cardiac arrest and to restore brain electrical activity during hypoglycemic coma in rabbits. In view of these findings, we determined whether fructose-1,6-diphosphate protects the brain during ischemia-hypoxia. We subjected 16 rabbits to hypotension, hypoxemia, and bilateral common carotid artery occlusion. Five minutes after the onset of isoelectric electroencephalograms, seven randomly selected rabbits received 10% fructose-1,6-diphosphate (350 mg/kg bolus followed by 10 mg/kg/min infusion for 90 minutes) and the remaining nine rabbits (controls) received an equal volume of 1.5% NaCl (3.5 ml/kg bolus followed by 0.1 ml/kg/min infusion for 90 minutes). After isoelectricity lasting 7.86 +/- 0.8 minutes (mean +/- SEM) in the treated group and 6.44 +/- 0.38 minutes in the control group, the rabbits were reinfused with autologous shed blood and reoxygenated and the carotid artery occluders were removed. Treated rabbits recovered electrical activity more rapidly than the controls (p less than 0.005), and all seven treated rabbits survived. Only two controls (22%) survived (p less than 0.001), and they were severely disabled. Histology showed extensive cortical necrosis and focal necrosis in the hippocampi and cerebellum of brains from the two surviving controls. Brains from two treated rabbits exhibited minimal neuronal loss limited to the neocortex, and the brains from the remaining five treated rabbits were normal. This study suggests that fructose-1,6-diphosphate protects the brain from ischemic-hypoxic insults.