bluuebunny/crossref_metadata_2025_split huggingface dataset:
Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats.
Authors: Sirén A L , Heldman E , Doron D , Lysko P G , Yue T L , Liu Y , Feuerstein G , Hallenbeck J M 
Published: June 2011

We reported previously that stroke risk factors prepared the brain stem for the development of ischemia and hemorrhage and induced the production of tumor necrosis factor following an intrathecal injection of lipopolysaccharide, a prototypic monocyte-activating stimulus. This study evaluates whether blood or brain cells of hypertensive rats produce more proinflammatory and prothrombotic mediators than do blood or brain cells of normotensive rats.
Levels of tumor necrosis factor, platelet-activating factor, 6-ketoprostaglandin F1 alpha, and thromboxane B2 in the cerebrospinal fluid and blood of spontaneously hypertensive and normotensive Wistar-Kyoto rats were monitored before and after a challenge with lipopolysaccharide.
Little or no activity from these mediators was found in the cerebrospinal fluid or blood of saline-injected control animals. Intravenous administration of lipopolysaccharide (0.001, 0.1, and 1.8 mg/kg) produced dose-dependent increases in blood levels of all mediators in hypertensive rats. In normotensive rats the levels were less than in hypertensive rats and were not clearly dose-related. When lipopolysaccharide was injected intracerebroventricularly, more tumor necrosis factor was measured in the cerebrospinal fluid than in the blood, suggesting local synthesis of this cytokine. Levels of tumor necrosis factor and platelet-activating factor in the cerebrospinal fluid were higher in hypertensive than in normotensive rats. The thromboxane A2/prostacyclin ratio was not altered significantly between the two rat strains.
It is suggested that the higher incidence of brain stem ischemia and hemorrhage after the intrathecal injection of lipopolysaccharide in hypertensive rats than in normotensive rats might be related to the higher levels of the two cytotoxic factors tumor necrosis factor and platelet-activating factor produced in response to such challenge.
Leukoaraiosis and dementia in hypertensive patients.
Authors: Yao H , Sadoshima S , Ibayashi S , Kuwabara Y , Ichiya Y , Fujishima M 
Published: June 2011

Although our previous study demonstrated that dementia of the Binswanger type may be a disconnection dementia caused by leukoaraiosis, some hypertensive patients with marked leukoaraiosis do not develop dementia. The goal of the present study is to elucidate the pathophysiology of nondemented hypertensive patients with leukoaraiosis.
We performed clinical and neuroradiological studies, including positron emission tomography, in eight hypertensive patients with leukoaraiosis.
Four patients were demented, and two among the other four who were not demented at the first examination developed dementia during the follow-up period. Digital subtraction angiography of the cervical and intracranial arteries demonstrated stenotic lesions in only one patient. Cerebral blood flow and oxygen metabolism in patients with dementia were markedly reduced in the white matter (59-67% of control values). In contrast, cerebral blood flow in the white matter of patients without dementia was reduced less markedly (74% of control), oxygen extraction fraction in the white matter was significantly increased (130% of control), and oxygen metabolism remained at almost-normal levels not only in the white matter but also in the cortical area.
Hypertension-caused arteriosclerotic changes of the long penetrating medullary arteries may cause misery perfusion and later ischemic damage in the periventricular white matter. Preserved oxygen metabolism in hypertensive patients with leukoaraiosis may represent the early stage of vascular dementia of the Binswanger type.
Longitudinal study of regional cerebral blood flow changes in depression after stroke.
Authors: Yamaguchi S , Kobayashi S , Koide H , Tsunematsu T 
Published: June 2011

We studied 60 patients longitudinally to examine relations between regional cerebral blood flow and depressive states after stroke.
Poststroke depressive states were assessed by the Zung Self-Rating Depression Scale (SDS). Regional cerebral blood flow was measured using the 133xenon inhalation method with patients in the resting state on the same day as the SDS assessment. All patients were followed for an average of 14 months after the initial assessment.
Severity of depression was inversely correlated with regional cerebral blood flow values in the parieto-occipital regions of the right hemisphere and in the anterior temporal region of the left hemisphere at the initial evaluation. Patients with lesions in left frontal or right parieto-occipital regions were more depressive in comparison with those with other brain lesions. Follow-up study showed significant inverse correlations between changes in SDS score and changes in regional cerebral blood flow at all scalp sites. Furthermore, higher inverse correlations were observed at specific brain regions in each hemisphere, including the parietal and parieto-occipital regions of the right hemisphere and the anterior temporal and inferior frontal regions of the left hemisphere. This relation was independent of recovery from neurological deficits.
These results suggest that dysfunction of specific cortical and subcortical regions in both hemispheres asymmetrically contributes to depressive state after stroke.
Critical limits of pressure-flow relation in the human brain.
Authors: Njemanze P C 
Published: June 2011

This study was designed to determine the minimal mean flow velocity and pressure-flow relation necessary to preserve human consciousness.
Passive upright tilt provocation was used in conjunction with transcranial Doppler in 80 patients with a history of syncope of unknown etiology. Cerebral blood flow velocity, blood pressure, and heart rate were monitored noninvasively.
Forty patients remained asymptomatic, and the rest had clinically induced true syncope or premonitory symptoms. In the asymptomatic group, there was a 23 +/- 16% (p = 0.000) drop in mean flow velocity, but no significant changes in systolic and diastolic blood pressures. In the symptomatic patients, there was a 58 +/- 14% (p = 0.000) drop in mean flow velocity, 37 +/- 23% (p = 0.000) fall in systolic pressure, and 31 +/- 20% (p = 0.000) fall in diastolic pressure. In 80% of symptomatic patients, the critical lower limit of mean flow velocity was at -50% of resting baseline while patients were lying supine. The symptomatic group had lower mean flow velocity and blood pressure responses as compared with the asymptomatic group. The slope and intercept values of the pressure (y axis) to flow velocity (x axis) regression curves indicate a greater degree of impaired autoregulation in the symptomatic group (y = 0.529 x-6.11, r2 = 0.108, p = 0.038) as compared with the asymptomatic (y = 0.317 x + 0.966, r2 = 0.14, p = 0.017).
The critical lower limit of cerebral perfusion lies at 50% below baseline supine mean flow velocity.
Effects of retrograde perfusion of the brain with combined drug therapy after focal ischemia in rat brain.
Authors: Shimauchi M , Yamamoto Y L 
Published: June 2011

The ischemic edema associated with blood-brain barrier permeability changes and the excess production of free radicals are serious complications in prolonged cerebral ischemia. We examined the efficacy of transvenous perfusion of the brain, starting treatment 5 hours after occlusion of the middle cerebral artery for a period of 2 hours in rats with the combined agents mannitol (10 ml/2 hr) and dexamethasone (1 mg/2 hr) to counter edema and verapamil (0.05 mg/kg/2 hr) for vasodilation.
In experiment 1, blood-brain barrier permeability changes were examined in five groups with six rats each: group C rats underwent 7 hours of middle cerebral artery occlusion with no treatment; group V, treatment with verapamil alone; group VD, treatment with verapamil and dexamethasone; group VM, treatment with verapamil and mannitol; and group VDM, treatment with verapamil, dexamethasone, and mannitol. In experiment 2, we examined local cerebral blood flow, ischemic tissue damage volume, and water content of cerebral hemispheres in two groups of 16 rats each subjected to the same treatment as groups C and VDM rats in experiment 1.
There was a significant reduction of blood-brain barrier permeability changes in the ischemic cortex of rats in group VDM compared with rats in the other groups. In the group undergoing transvenous perfusion of the brain with the three combined agents, there was a significant improvement of cerebral blood flow (39-58%, p < 0.05) in the ischemic cortex and reduction of ischemic cerebral damage volume (22%, p < 0.01) and water content of the ischemic hemisphere (p < 0.05) compared with the control group.
The therapeutic approach using combined agents is effective treatment when initiated within 5 hours of focal cerebral ischemia in rats.
Long-term prognosis of infratentorial transient ischemic attacks and minor strokes.
Authors: Hornig C R , Lammers C , Büttner T , Hoffmann O , Dorndorf W 
Published: June 2011

This study was performed to gather information about long-term prognosis after infratentorial transient ischemic attacks and minor strokes and about the factors influencing it.
We included 226 patients with transient ischemia and 169 patients with a minor stroke of the brain stem/cerebellum consecutively admitted to a neurological department. Medical records and the findings of computed tomography, Doppler ultrasonography, and angiography were evaluated retrospectively. Follow-up information was gathered from the patients and their physicians by questionnaires. Complete follow-up information was available for 381 patients.
During a mean follow-up of 3.9 years, 15.7% of the 381 patients suffered a stroke and 6.8% a myocardial infarction; 15% died. Kaplan-Meier estimates revealed a cumulative stroke rate of 5.1% within the first year and a risk of stroke, myocardial infarction, or death of any cause of 9.8%. In a proportional hazards model, the time-dependent risk of stroke was significantly increased by increasing age (p = 0.018), minor stroke (p = 0.0005), hypertension (p = 0.022), previous stroke (p = 0.0006), and carotid artery occlusive disease (p = 0.0065). The probability of stroke, myocardial infarction, or death was influenced by age (p = 0.0001), minor stroke (p = 0.006), diabetes (p = 0.015), previous stroke (p = 0.002), infarct on a computed tomogram (p = 0.041), and carotid artery disease (p = 0.032).
Long-term prognosis after brain stem/cerebellar transient ischemic attacks and minor strokes is significantly influenced by age, diabetes, hypertension, previous stroke, and concomitant carotid artery disease. Patients with transient ischemic attacks have a better prognosis than those with minor stroke.
Delayed onset hand tremor caused by cerebral infarction.
Authors: Kim J S 
Published: June 2011

Hand tremor has been rarely described as a manifestation of stroke.
Three patients developed delayed onset hand tremor due to cerebral infarctions on the contralateral side, two in the caudate nucleus and the third in the thalamus. The tremors of all three patients were similar to parkinsonian tremor, but less monotonous.
Delayed-onset hand tremor should be considered as one of the movement disorders caused by cerebral infarction.
Cerebral infarction in young men with nephrotic syndrome.
Authors: Fuh J L , Teng M M , Yang W C , Liu H C 
Published: June 2011

Thrombosis is one of the main complications of nephrotic syndrome; however, cerebral infarction associated with nephrotic syndrome has been rarely reported.
We describe acute cerebral infarction in two young men with nephrotic syndrome. Both had a hypercoagulable state based on hemostatic studies. By retrospectively reviewing the medical records of the past 10 years at our hospital, we found an additional five cases of cerebral infarction with nephrotic syndrome. Two of the patients were found to have nephrotic syndrome during admission for stroke.
Hypercoagulability may be the major contributing factor of cerebral infarction in patients with nephrotic syndrome.
Blood flow and vascular permeability during motor dysfunction in a rabbit model of spinal cord ischemia.
Authors: Jacobs T P , Kempski O , McKinley D , Dutka A J , Hallenbeck J M , Feuerstein G 
Published: June 2011

Delayed deterioration of neurological function after central nervous system ischemia is a well-documented clinical problem. The purpose of our study was to elucidate the role of spinal cord blood flow and spinal cord-blood barrier integrity in the evolution of delayed neurological deterioration after transient spinal cord ischemia in rabbits.
Anesthetized rabbits were subjected to lumbar spinal cord ischemia (25 minutes) and variable periods of reperfusion (30 minutes to 48 hours after ischemia). Regional spinal cord blood flow was monitored by carbon-14-labeled iodoantipyrine autoradiography; vascular permeability was assessed by quantitative microhistofluorescence of Evans blue-albumin in frozen sections of spinal cord. Hindlimb motor function was assessed by standard scoring system and tissue edema by wet/dry weight method.
Hindlimb motor function indicated complete paralysis during ischemia and partial gradual recovery upon reperfusion (up to 8 hours), followed by progressive deterioration to severe deficits over 48 hours. Severe vascular permeability disruption was noticed early (30 minutes) after reperfusion, but almost complete recovery reestablished at 8 hours was followed by a secondary progressive increase in vascular permeability. Blood flow was reduced by 20-30% (p less than 0.01) 4 hours after ischemia in the gray matter, but hyperemia (200-300%, p less than 0.01) was observed 12-24 hours after ischemia. Spinal cord water content increased by 5.7% (p less than 0.05) 24 hours after ischemia.
This study demonstrates that delayed neurological and motor deterioration after spinal cord ischemia is associated with severe progressive breakdown of spinal cord-blood barrier integrity that develops late (hours) after the injury. Our data suggest that no ischemic insult in early or late reperfusion is associated with delayed motor deterioration.
Tissue plasminogen activator cerebrovascular thrombolysis in rabbits is dependent on the rate and route of administration.
Authors: Russell D , Madden K P , Clark W M , Zivin J A 
Published: June 2011

The main aim of our study was to assess the cerebrovascular thrombolytic efficacy of different tissue plasminogen activator treatment protocols with Doppler ultrasound.
We occluded one internal carotid artery in 48 New Zealand White rabbits with whole blood emboli. Five minutes later the rabbits were assigned to receive one of the following tissue plasminogen activator protocols: 1) intravenous square-wave infusion in a total dose of 10 mg/kg, 2) intravenous constant infusion in a total dose of 10 mg/kg, 3) intravenous square-wave infusion in a total dose of 3 mg/kg, or 4) regional intra-arterial square-wave infusion in a total dose of 3 mg/kg. Blood flow velocities in the internal carotid arteries were continuously monitored during the study with Doppler ultrasound.
In all 12 animals treated with a 10-mg/kg square-wave intravenous tissue plasminogen infusion, internal carotid artery blood flow was reestablished within 2 hours (57.9 +/- 33.3 minutes) after the initiation of treatment, whereas this was the case for only six (50%) of the 12 animals treated with a constant 10-mg/kg intravenous tissue plasminogen activator infusion (p less than 0.05, Fisher's exact test). Internal carotid artery blood flow was restored within 2 hours (33.5 +/- 40.4 minutes) in all animals treated with a regional intra-arterial tissue plasminogen infusion in a total dose of 3 mg/kg and in only three (50%) of the six animals treated with the same dosage intravenously (p less than 0.05, signed rank test).
The thrombolytic efficacy of tissue plasminogen activator in the rabbit cerebral vasculature was superior when the same intravenous dose was given as a square-wave rather than a constant infusion and when the drug was given as a regional intra-arterial infusion rather than intravenously.
Effect of hemodilution on cerebral hemodynamics and oxygen metabolism.
Authors: Hino A , Ueda S , Mizukawa N , Imahori Y , Tenjin H 
Published: June 2011

To evaluate the effects of hemodilution on cerebral hemodynamics and oxygen metabolism in the normal human brain, we measured regional cerebral blood flow, oxygen extraction fraction, oxygen metabolic rate, and regional cerebral blood volume in eight normal volunteers before and after hemodilution using positron emission tomography and oxygen-15-labeled gas inhalation technique.
Hemodilution was accomplished by phlebotomy of 400 ml and drip infusion of 500 ml low molecular weight dextran, which reduced hematocrit from 42.5% to 37.2% and arterial oxygen content from 19.1 to 16.9 ml/dl (both p less than 0.005). It also increased mean cerebral blood flow from 45.2 to 47.7 ml/100 ml/min (p less than 0.025), but decreased tissue oxygen delivery from 8.7 to 8.0 ml/100 ml/min (p less than 0.05) and cerebral blood volume from 4.9% to 4.6% (p less than 0.025) in the overall cortical gray matter.
Our results indicate that hemodilution in the tested range does not improve oxygen transport or tissue oxygenation in the normal human brain, although it increases cerebral blood flow.
Protective effects of felbamate against hypoxia in the rat hippocampal slice.
Authors: Wallis R A , Panizzon K L , Fairchild M D , Wasterlain C G 
Published: June 2011

Felbamate is a new dicarbamate anticonvulsant with low toxicity currently being investigated in human clinical epilepsy trials. In this study, we examined the protective effects of felbamate against hypoxia.
We exposed paired rat hippocampal slices to hypoxia with and without felbamate treatment while monitoring the CA1-evoked population spike.
Felbamate provided dose-dependent neuroprotection against hypoxia at concentrations of 45 mg/l and greater (p less than 0.05). At a felbamate concentration of 300 mg/l, recovery of CA1 evoked population spike amplitude after hypoxic exposure was 99% compared with 0.5% for unmedicated paired slices. The appearance and disappearance of the hypoxic injury potential was delayed in slices treated with 300 and 400 mg/l (p less than 0.05).
In this model of hypoxia, felbamate provided neuroprotection against hypoxia at concentrations similar to serum felbamate levels currently being used in human clinical epilepsy trials.
Surgical correction and SPECT imaging of vertebrobasilar insufficiency due to unilateral vertebral artery stenosis.
Authors: Comerota A J , Maurer A H 
Published: June 2011

Incapacitating vertebrobasilar insufficiency is generally associated with bilateral vertebral artery disease, whereas unilateral vertebral artery stenosis usually is clinically silent. Regional brain perfusion has not been part of the routine evaluation of patients with vertebrobasilar insufficiency. This report describes two patients who had isolated unilateral vertebral artery stenosis operatively corrected to eliminate their incapacitating vertebrobasilar insufficiency. Hindbrain hypoperfusion was identified preoperatively and evaluated postoperatively, then correlated with patient presentation and response to revascularization.
Two patients with incapacitating vertebrobasilar insufficiency presented with isolated unilateral vertebral artery stenosis with patent, nonstenotic internal carotid arteries. Hindbrain hypoperfusion was demonstrated by iodine-123-iodoamphetamine single-photon emission computed tomography preoperatively and demonstrated significant improvement following vertebral-carotid reimplantation. The patients' symptoms resolved following revascularization.
Although unusual, unilateral vertebral artery stenosis can cause incapacitating vertebrobasilar insufficiency. These cases demonstrate the value of imaging with single-photon emission computed tomography to evaluate regional brain hypoperfusion and to evaluate objectively the results of therapy.
Urgent therapy for stroke. Part I. Pilot study of tissue plasminogen activator administered within 90 minutes.
Authors: Brott T G , Haley E C , Levy D E , Barsan W , Broderick J , Sheppard G L , Spilker J , Kongable G L , Massey S , Reed R 
Published: June 2011

Thrombolytic agents hold theoretical promise as therapy for cerebral infarction. This study was designed to evaluate the safety of tissue plasminogen activator, to accomplish urgent patient treatment, and to estimate potential efficacy of tissue plasminogen activator.
Following neurological evaluation and computed tomography of the brain, patients with acute ischemic stroke were evaluated and treated with intravenous tissue plasminogen activator under an open-label, dose-escalation design within 90 minutes from symptom onset. End points examined included symptomatic and asymptomatic intracranial hematoma, systemic hemorrhage, and neurological outcome at 2 hours, 24 hours, and 3 months.
Seventy-four patients were treated within 90 minutes of symptom onset over seven dose tiers of tissue plasminogen activator, ranging from 0.35 mg/kg to 1.08 mg/kg. Intracranial hematoma with associated neurological deterioration occurred in three patients and was related to increasing doses of tissue plasminogen activator (p = 0.045). Intracranial hematoma did not occur in any of the 58 patients treated with less than or equal to 0.85 mg/kg. Major neurological improvement occurred in 22 patients (30%) at 2 hours from the initiation of tissue plasminogen activator and in a total of 34 patients (46%) at 24 hours, but major neurological improvement was not related to increasing doses of tissue plasminogen activator or to stroke type.
Patients with acute stroke can be evaluated and treated within 90 minutes. Tissue plasminogen activator for acute ischemic infarction is not without risk, but the potential for clinical benefit justifies a randomized clinical trial. To date, differences in hemorrhagic risk or neurological benefit of tissue plasminogen activator for particular ischemic stroke types are not apparent.
Transesophageal echocardiographic detection of aortic arch disease in patients with cerebral infarction.
Authors: Amarenco P , Cohen A , Baudrimont M , Bousser M G 
Published: June 2011

Ulcerated plaques in the aortic arch are frequent autopsy findings in patients with cerebral infarctions, particularly those of unknown cause. It has been suggested that they could be a source of cerebral emboli. Using transesophageal echocardiography, we prospectively studied 12 consecutive patients with cerebral infarction of undetermined cause after noninvasive workup to evaluate the frequency of aortic plaques or mural thrombi that could embolize in cerebral arteries.
Six patients (50%) had an intraluminal echogenic mass of the aortic arch, mainly located at the junction of the ascending aorta and arch. This material was pedunculated (in one patient) or broad based (in five patients) with a markedly irregular surface and intraluminal extension from 3 to 15 mm. In addition, we found cholesterol emboli in two of the four patients who underwent quadriceps biopsy.
These results show that transesophageal echocardiography has capabilities in detecting such lesions and point to the aortic arch as a possible source of cerebral emboli in patients with cerebral infarction of unknown cause.