bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and prognosis of stroke in the Valle d'Aosta, Italy. First-year results of a community-based study.
Authors: D'Alessandro G , Di Giovanni M , Roveyaz L , Iannizzi L , Compagnoni M P , Blanc S , Bottacchi E
Published: June 2011

We sought to determine the incidence rate, risk factors, and prognosis of stroke in Valle d'Aosta, Italy, to provide information for planning regional health-care facilities.

We undertook a prospective study of all new cases of stroke in the geographically defined population of 114,325 residents of Valle d'Aosta in northern Italy.

In the first year of the study (January 1-December 31, 1989), 254 cases of first stroke were registered. The crude annual incidence rate was 2.23/1,000, 1.98/1,000 for men and 2.46/1,000 for women. After adjustment to the 1988 Italian population, the incidence rate for first stroke was 2.15/1,000 per year, 2.48/1,000 per year for men and 1.99/1,000 per year for women. The pathological diagnosis was cerebral infarction in 67%, intracranial hemorrhage in 15%, and unknown in 18%. The overall 30-day case-fatality rate was 31%. In survivors, Barthel Index Score recorded at 30 days from stroke onset showed that 100 patients (62%) were dependent in activities of daily living.

Our results do not differ significantly from those reported in Umbria, the only similar study performed in Italy, and support non-Italian data as to risk factors in stroke.
Antioxidants attenuate microvascular changes in the early phase of experimental pneumococcal meningitis in rats.
Authors: Pfister H W , Koedel U , Lorenzl S , Tomasz A
Published: June 2011

We tested in a rat meningitis model 1) whether pneumococcal cell wall components are capable of producing changes in regional cerebral blood flow, brain water content, and intracranial pressure similar to those we have already observed after intracisternal inoculation of live pneumococci and 2) whether antioxidants would modulate these alterations in the early phase of meningitis.

Regional cerebral blood flow as measured by laser Doppler flowmetry and intracranial pressure were monitored continuously for 4 hours after intracisternal challenge. Brain edema formation was assessed by brain water content determinations. We investigated the following groups: rats challenged intracisternally with the whole intact pneumococcal cell wall (n = 7) or the pneumococcal cell wall hydrolyzed by the M1-muramidase (n = 7); rats injected intracisternally with phosphate-buffered saline (n = 6); rats pretreated intravenously with superoxide dismutase conjugated with polyethylene glycol (10,000 units/kg) and injected intracisternally with cell wall components (n = 5) or phosphate-buffered saline (n = 6); rats injected intracisternally with phosphate-buffered saline and pretreated intravenously with polyethylene glycol (10% solution, 1.2 ml/kg, n = 5) or continuously treated with intravenous free superoxide dismutase (22,000 units/kg per hour, n = 6); and rats continuously treated intravenously with deferoxamine mesylate (10 mg/kg per hour) and injected intracisternally with cell wall components (n = 6) or phosphate-buffered saline (n = 7).

Both pneumococcal cell wall preparations produced a significant increase in regional cerebral blood flow, intracranial pressure, and brain water content. Conjugated superoxide dismutase as well as deferoxamine prevented the increase in intracranial pressure and brain water content. In addition, the increase in regional cerebral blood flow as observed in untreated, cell wall-challenged rats (baseline, 100%; 183.1 +/- 12.3% after 4 hours, mean +/- SEM) was significantly attenuated by administration of both conjugated superoxide dismutase (136.6 +/- 14.1%) and deferoxamine (149.8 +/- 8.2%) (p < 0.05). Polyethylene glycol-conjugated superoxide dismutase alone produced an increase in regional cerebral blood flow (125.6 +/- 8.7% after 4 hours). We found that polyethylene glycol per se accounts for this action.

These data show that pneumococcal cell wall components containing teichoic acid produce changes in regional cerebral blood flow, intracranial pressure, and brain water content and that oxygen radicals contribute to these pathophysiological alterations in the early phase of experimental pneumococcal meningitis.
Cerebral infarction in a heterozygote with variant antithrombin III.
Authors: Arima T , Motomura M , Nishiura Y , Tsujihata M , Okajima K , Abe H , Nagataki S
Published: June 2011

We report a heterozygous case of familial qualitative deficiency of antithrombin III associated with cerebral infarction.

A 33-year-old man had a history of recurrent transient ischemic attacks from the age of 28. Cerebral computed tomography at age 29 disclosed a low-density area in the left frontal lobe, and an internal carotid angiogram showed branch occlusion of the right anterior cerebral artery and stenosis of the left middle cerebral artery. Occlusion of the right middle cerebral artery developed thereafter. The plasma antithrombin III antigen concentration and progressive antithrombin activity were normal, but plasma heparin cofactor activity was low in the patient and his father. Nucleotide sequence analysis of the proband's deoxyribonucleic acid showed no mutation in exons II and VI of antithrombin III.

We conclude that abnormal antithrombin III with defective heparin binding, even though heterozygous, may cause ischemic stroke in young adults. We named this antithrombin III variant "Antithrombin III Nagasaki."
Transcranial Doppler sonography monitoring of local intra-arterial thrombolysis in acute occlusion of the middle cerebral artery.
Authors: Karnik R , Stelzer P , Slany J
Published: June 2011

The aim of this study is to report on the use of transcranial Doppler ultrasonography as a noninvasive diagnostic monitoring tool during local intra-arterial thrombolysis in a patient with acute embolic occlusion of the middle cerebral artery.

We describe a 41-year-old woman with mitral valve stenosis suffering from embolism of the middle cerebral artery. Local thrombolysis was performed with tissue plasminogen activator at a dosage of 0.05 mg/kg/hr. Progress of the thrombolysis was monitored by transcranial Doppler. The steps of recanalization could be ascertained by transcranial ultrasound showing a hemodynamically relevant residual stenosis after the first 120 minutes and complete patency of the M1 segment of the middle cerebral artery 180 minutes later. One branch of the middle cerebral artery still showed a filling defect.

Our report demonstrates the potential usefulness of transcranial Doppler monitoring during thrombolysis of a proximal occlusion of the middle cerebral artery for guiding the treatment by assessing the reperfusion of the obstructed artery.
Supraventricular tachycardia in patients with right hemisphere strokes.
Authors: Lane R D , Wallace J D , Petrosky P P , Schwartz G E , Gradman A H
Published: June 2011

The physiological basis for the arrhythmias commonly observed after a stroke is not well understood. Based on evidence that the right and left cerebral hemispheres influence cardiac function in different ways, we sought to determine whether the nature and severity of cardiac arrhythmias in the context of an acute stroke vary in relation to whether the stroke is located in the left or the right hemisphere.

Data were obtained from the medical records of nineteen patients with left hemisphere strokes and nineteen patients with right hemisphere strokes who had also had 24-hour electrocardiographic (Holter) recordings within 2 weeks of admission to a stroke unit. Written Holter monitor reports already on file were used for the data analysis.

All four patients with supraventricular tachycardia had right hemisphere strokes (p = 0.05). There was a nonsignificant trend for left hemisphere stroke patients to have more severe ventricular arrhythmias.

These data provide partial support for the hypothesis that the two cerebral hemispheres have a differential influence on the nature and severity of arrhythmias following an acute stroke. We speculate that parasympathetic tone was diminished ipsilateral to the affected hemisphere associated with a reciprocal rise in sympathetic tone on that side and recommend that a prospective study be undertaken to test this hypothesis more definitively.
Study of platelet-mediated neurotoxicity in rat brain.
Authors: Joseph R , Tsering C , Welch K M
Published: June 2011

The mechanism of ischemic neuronal injury is not fully resolved. The present view is that vascular occlusion per se does not fully account for the extent of neurological dysfunction. We previously hypothesized that platelet secretory products might contribute to neuronal injury in the central nervous system. Our preliminary studies using organotypic rat spinal cord cultures exposed to human platelet and its secretory products revealed that platelet products had neurotoxic properties.

Further studies, using the same methods, were conducted, with the addition of several refinements such as use of gel-filtered platelets (as opposed to washed platelets) and adding additional relevant controls including platelet membranes, red blood cells, and washed rat platelets.

Exposure of spinal cord explant cultures to platelet secretory products resulted in reduced number of neurons per ventral horn compared with control.

Our findings suggest that platelet secretory products have neurotoxic properties. This effect was seen with platelet secretion obtained from physiological platelet concentrations. It appears possible that more abundant release of platelet products at the site of thrombus formation could have pathological significance in vivo.
Effect of endothelin on production of cerebrospinal fluid in rabbits.
Authors: Schalk K A , Faraci F M , Heistad D D
Published: June 2011

Endothelin is a potent vasoconstrictor in several tissues, including the choroid plexus. The goal of this study was to determine whether endothelin affects the production of cerebrospinal fluid.

Ventriculocisternal perfusion was used to measure the production of cerebrospinal fluid in anesthetized rabbits. Changes in production of cerebrospinal fluid were examined in response to vehicle, intravenous endothelin (alone and in the presence of indomethacin), and intraventricular endothelin.

Under control conditions, the reduction in production of cerebrospinal fluid in response to endothelin administered intravenously was only modestly greater than that during infusion of vehicle. Because endothelin releases cyclooxygenase products that attenuate the direct effects of endothelin in several tissues, effects of endothelin on the production of cerebrospinal fluid were also examined after inhibition of cyclooxygenase. Production of cerebrospinal fluid in response to 1 micrograms/kg i.v. endothelin was reduced more in animals treated with indomethacin than in untreated animals (-34 +/- 7% [mean +/- SEM] versus -14 +/- 6%, p less than 0.05). Thus, effects of endothelin on the production of cerebrospinal fluid are attenuated by cyclooxygenase products. Finally, responses to intraventricular endothelin were examined. Intraventricular endothelin produced a modest, but significant, reduction in the production of cerebrospinal fluid.

In summary, endothelin may play a role in regulation of the brain fluid balance by affecting the rate of production of cerebrospinal fluid, and this effect is modulated by cyclooxygenase products.
Comparison of multicenter study designs for investigation of carotid endarterectomy efficacy.
Authors: Howard V J , Grizzle J , Diener H C , Hobson R W , Mayberg M R , Toole J F
Published: June 2011

Our report summarizes and compares the characteristics of six prospective, multicenter, randomized clinical trials of carotid endarterectomy underway in North America and Europe.

Three trials are designed to evaluate the safety and efficacy of endarterectomy in patients with asymptomatic carotid artery stenosis. The other three trials enroll patients who have had transient ischemic attacks or a minor cerebral infarction in the distribution of the randomized artery. Considered together, these six clinical trials span the range of candidates for carotid endarterectomy. The inclusion and exclusion criteria, methodology, and statistical considerations of each study are detailed in tables.

The results from these trials will be helpful in resolving some of the questions surrounding endarterectomy, provided the similarities and differences in the study designs are considered when interpreting the results.
Are hemostatic factors responsible for the paradoxical risk factors for coronary heart disease and stroke?
Authors: Gliksman M , Wilson A
Published: June 2011

The paradoxical occurrence of a high risk of stroke in some populations at low risk for coronary heart disease has long been known. Recently, evidence has appeared linking the paradoxical risk to population-based differences in diet, serum cholesterol, and alcohol intake. However, the pathophysiological mechanism of action that would explain this paradox is unlikely to be atherosclerosis alone.

Several recent cross-sectional and prospective population studies have shown that hemostatic factors vary between populations in a manner consistent with the paradox. Studies have also shown that certain hemostatic factors are independent predictors of risk of coronary heart disease, ischemic stroke, and, probably, hemorrhagic stroke.

Risk factors that enhance thrombosis and reduce fibrinolysis are capable of explaining the paradoxical occurrence of the incidence of coronary heart disease and stroke in certain populations.
Safety and efficacy of intravenous tissue plasminogen activator and heparin in acute middle cerebral artery stroke.
Authors: von Kummer R , Hacke W
Published: June 2011

There is little reported of the safety and efficacy of high-dose intravenous recombinant tissue plasminogen activator (alteplase) in combination with heparin anticoagulation in patients presenting with acute ischemic stroke.

Thirty-two patients with severe hemispheric stroke syndrome caused by angiographically proven middle cerebral artery and/or intracranial internal carotid artery occlusion were treated with 100 mg alteplase by intravenous infusion over 90 minutes within a mean +/- SD of 226 +/- 68 minutes after symptom onset. Recanalization was assessed by digital subtraction angiography in all patients immediately after treatment and by transcranial Doppler monitoring (n = 30) and/or a third angiogram (n = 5) 12-24 hours later.

Complete or partial reperfusion was observed in 11 patients (34%) 90 minutes after the initiation of alteplase infusion and in 17 patients (53%) within 12-24 hours. Hemorrhagic infarction without clinical deterioration was detected by follow-up computed tomography in nine patients (28%). Fatal parenchymal hemorrhage occurred in three patients (9%) with huge middle cerebral artery infarcts. Serious hemorrhage from the puncture site occurred in two patients (6%). Good clinical outcome correlated with reperfusion (p less than 0.05) and the presence of grade 2 collateral blood flow (p less than 0.01).

When 100 mg of recombinant tissue plasminogen activator was given within the first 6 hours of acute stroke together with heparin the incidence of deleterious hemorrhage was less than 10%. Reperfusion and effective collateral blood flow seem to be two important factors associated with a small infarct volume and good clinical outcome.
Patterns of cerebral hypoperfusion compared among demented and nondemented patients with stroke.
Authors: Terayama Y , Meyer J S , Kawamura J , Weathers S , Mortel K F
Published: June 2011

No reports are available that compare local cerebral perfusion among groups of patients suffering from multiple cerebral infarctions with and without cognitive impairments. The present study was designed to correlate changes in regional cerebral perfusion that may lead to dementia among patients with multiple cerebral infarctions by comparing measurements of local cerebral blood flow.

Local perfusion was measured using xenon-contrasted computed tomographic scanning among two groups of patients who had suffered from multiple cerebral infarctions: Group D (n = 12) were demented and had severe cognitive impairments, and group I (n = 11) were cognitively intact. Results were compared with similar measurements among neurologically and cognitively normal, age-matched volunteers (group N, n = 16).

Mean local perfusion values were reduced among both groups with cerebral infarctions but to a more marked degree in group D (p less than 0.05). Perfusion of cerebral white matter was diffusely and severely reduced in group D (p less than 0.05) but was mildly reduced only in frontal and capsular white matter in group I (p less than 0.05). Perfusion of cerebral cortex was reduced in frontal (p less than 0.01) and temporal (p less than 0.01) regions among both groups but to a significantly greater degree in group D subjects (frontal, p less than 0.05; temporal, p less than 0.01), who also showed hypoperfusion of the occipital cortex (p less than 0.05), apparently because of underlying leukoaraiosis and cortical disconnections. Perfusion of the basal ganglia was reduced to the same degree among both groups of stroke patients (p less than 0.01).

Leukoaraiosis with white matter hypoperfusion appears to be an important determinant for cognitive impairments among patients with multiple cerebral infarctions.
Factors delaying hospital admission after stroke in Leicestershire.
Authors: Harper G D , Haigh R A , Potter J F , Castleden C M
Published: June 2011

Use of thrombolysis and acute treatments for cerebral infarction may require that acute stroke be treated as a medical emergency. To assess the factors influencing the time to admission in acute stroke, we conducted a prospective study of all such patients admitted to the hospitals in Leicester, UK, over a 12-month period.

Factors assessed were age, sex, time of stroke onset, stroke severity, home circumstances, and routes of admission. Initial between-group comparisons were made with the Mann-Whitney U test. The individual contribution of each of these variables was assessed with multiple linear regression analysis.

An accurate time of stroke onset was identified in 374 (70%) of 535 registered patients (median age 77 [range, 29-98] years; 332 men, 203 women). Median time from onset to admission was 6 hours, with 25% of the patients arriving in less than 2.5 hours and 75% in less than 11.5 hours. Multiple regression confirmed that only admission through the bed allocation bureau (p less than 0.001), living alone (p less than 0.001), and nocturnal onset (p = 0.003) prolonged delay time. Despite patients over 70 years of age taking a median of 7 hours from onset to admission compared with 4 hours for those under age 70 (p less than 0.001), the effect of age appeared to be dependent on these three factors. Age, sex, level of consciousness, rural domicile, and place of admission did not influence the delay time independently.

We have identified some of the factors affecting the hospital admission delay time for stroke. With the possible advent of effective early treatments for stroke, these factors will need to be addressed.
Concomitants of asymptomatic retinal cholesterol emboli.
Authors: Bruno A , Russell P W , Jones W L , Austin J K , Weinstein E S , Steel S R
Published: June 2011

Asymptomatic retinal cholesterol emboli are sometimes encountered on ophthalmoscopic examination. They are associated with decreased survival, but their clinical significance is not fully known. We sought to determine which vascular risk factors are associated with such emboli.

We studied 70 consecutive men (55-84 years old) with asymptomatic retinal cholesterol emboli diagnosed in an eye clinic. Twenty-one men (57-78 years old) from the same eye clinic without retinal emboli or retinal ischemic events were randomly selected as control subjects. We determined vascular risk factors, presence of ischemic heart disease, and extracranial carotid artery disease.

Patients had a higher prevalence of hypertension, smoked more, and had a higher prevalence of heterogeneous or echolucent carotid plaques on either side than did control subjects (p less than 0.001 for all three factors). Patients also had a higher prevalence of carotid artery stenosis greater than or equal to 50% on either side and a higher prevalence of ischemic heart disease than did control subjects, but these did not reach statistical significance (p = 0.06 and p = 0.08, respectively).

Our findings suggest that hypertension and cigarette smoking may be important in the pathogenesis of asymptomatic retinal cholesterol emboli and that these emboli indicate systemic atherosclerosis rather than ipsilateral carotid artery stenosis.
Regional differences in rat brain lipids during global ischemia.
Authors: Chavko M , Nemoto E M
Published: June 2011

Membrane lipid degradation plays an important role in the pathogenesis of ischemic brain damage, but there is little information on changes in cerebrosides, sulfatides, and sphingomyelin. We studied regional changes in the quantities of these lipids during complete global brain ischemia in rats.

Nitrous oxide-anesthetized rats were subjected to ischemia by a high-pressure neck cuff and arterial hypotension for 0 (control), 3, 10, or 30 minutes (n = 5 at each time). Brain temperature was allowed to fall spontaneously during ischemia, and the brain was frozen in situ with liquid N2 without recirculation. The frontal cortex, hippocampus, and basal ganglia were dissected at -15 degrees C. The lipids were separated by column and high-performance thin-layer chromatography and quantified by charring and densitometry.

Total lipid content was higher (p less than 0.01) in the hippocampus (72.6 +/- 2.8 mg/g wet wt, mean +/- SD) than in the frontal cortex and basal ganglia (57.7 +/- 2.1 and 62.6 +/- 1.5 mg/g wet wt, respectively). Ischemic changes occurred only in the frontal cortex, where total lipid content fell (p less than 0.01) by 11% after 30 minutes of ischemia because sulfatide and cerebroside contents fell by 44% and 38%, respectively.

Despite a marked accumulation of free fatty acids during complete global brain ischemia in rats, the only detectable changes in brain lipids were in the amounts of cerebrosides and sulfatides in the frontal cortex.
Familial intracranial aneurysms. A review.
Authors: ter Berg H W , Dippel D W , Limburg M , Schievink W I , van Gijn J
Published: June 2011

A familial occurrence of intracranial aneurysms is defined by the presence of such aneurysms in two or more first to third-degree family members. Families with two affected members may represent accidental aggregation. Other families show a frequency compatible with an autosomal dominant mode of inheritance. A genetic basis is also suggested by the younger average age of familial cases with a ruptured intracranial aneurysm (42.3 years versus an age range of 50-54 years for nonfamilial cases), occurrence at the same site or a mirror site in sibling pairs, occurrence in identical twins, and the association of intracranial aneurysms with genetically transmitted disorders.

No reliable data are available about the occurrence of familial intracranial aneurysms among all patients with ruptured aneurysms; a frequency of 6.7% has been reported from a retrospective study, but a large part of the "familial" occurrence can be explained by fortuitous aggregation. The pathogenesis of familial intracranial aneurysms is not fully explained; a (partial) deficiency of type III collagen has been reported in sporadic, but not in familial, cases. Clinical decision analysis shows how the risk of harboring an intracranial aneurysm and the age of the patient are the main determinants for elective screening; lifetime risk of rupture (and therefore age) and surgical risks are the determinants for neurosurgical treatment.

Surgical treatment is recommended for patients aged less than 70 years with a moderate or low surgical risk, and screening (preferably by intra-arterial digital subtraction angiography) is recommended only for relatives aged 35-65 years. Magnetic resonance angiography may develop into a useful alternative for screening, but the risks of diagnostic procedures play only a minor role in the decision analysis.
Effects of cerebral angiomas on perifocal and remote tissue: a multivariate positron emission tomography study.
Authors: Fink G R
Published: June 2011

Using multitracer positron emission tomography, I investigated regional hemodynamic and metabolic changes in both perifocal and remote tissues of cerebral angiomas, with special reference to steal phenomena.

In 22 patients (14 with arteriovenous malformations and eight with cavernomas) cerebral blood flow, cerebral blood volume, mean vascular transit time, cerebral metabolic rate for oxygen, oxygen extraction fraction, cerebral metabolic rate for glucose, and glucose extraction fraction were measured using standard positron emission tomographic methods. Twelve patients also had their cerebral glucose metabolism assessed during psychophysical activation. Regions of interest representing the angioma, perifocal and remote tissues, contralateral mirror regions, and standard brain regions were analyzed.

There were no significant changes in hemodynamic variables or oxygen metabolism in the ipsilateral cerebral hemisphere, but ipsilateral glucose metabolism was reduced both at rest (p less than 0.01) and during activation (p less than 0.05). Glucose (p less than 0.001) and oxygen (p less than 0.001) metabolism in regions of perifocal tissue with low blood flow were decreased, with substrate extraction fractions showing no increase to compensate for insufficient blood flow. Functional recruitment of the cortex overlying the angioma beyond its periphery and supplied by the same arterial branches was subnormal (p less than 0.05) despite relatively unchanged hemodynamics in this tissue compartment.

These data suggest that dysfunction of the cortex supplied by arterial branches also feeding the vascular malformation is related to neuronal deafferentation, while the proportionate decrease in blood flow and metabolism of perifocal tissue may be ascribed to neuronal loss in chronically hypoperfused areas, rather than to persistent hemodynamic steal effects.
Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup.
Authors: Ment L R , Stewart W B , Ardito T A , Huang E , Madri J A
Published: June 2011

Although indomethacin has been demonstrated to prevent germinal matrix and intraventricular hemorrhage in clinical and animal studies, the mechanism of action of this agent to prevent hemorrhage remains unclear. Previous studies have demonstrated both that the microvessels in the germinal matrix of newborn beagle pups undergo basement membrane maturation during the first 4 postnatal days and that indomethacin may promote laminin deposition in tumor cell culture systems.

We employed the newborn beagle pup model to test the hypothesis that indomethacin may stimulate laminin deposition in germinal matrix microvessels. Newborn pups were randomized to receive either 0.1 mg/kg/dose i.p. indomethacin or an equal volume of saline diluent. Pups received doses of study medication once a day for 1, 2, or 3 days and were studied on postnatal days 1, 2, 3, or 4. Pups were anesthetized and systemically perfused with buffered formalin; the brains were removed and prepared for immunohistochemical study.

Sections stained with Bandeiraea lectin demonstrated that there was no difference in germinal matrix vessel density among the postnatal ages studied; similarly, there were no differences in vessel density between saline- and indomethacin-treated animals at any postnatal age. Quantification of germinal matrix stained intensity by confocal microscopy demonstrated significant increases in indomethacin-treated pups for both laminin staining at postnatal days 2 (p = 0.05) and 3 (p = 0.0009) and type V collagen staining at postnatal day 2 (p = 0.011). Although staining for beta 1 integrins increased across postnatal ages, there were no differences between saline- and indomethacin-treated animals.

These data suggest that indomethacin may stimulate basement membrane deposition in the germinal matrix microvessels of newborn beagle pups to prevent germinal matrix and/or intraventricular hemorrhage.
A phospholipase C inhibitor ameliorates postischemic neuronal damage in rats.
Authors: Umemura A , Mabe H , Nagai H
Published: June 2011

The hypothesis of calcium-induced neuronal damage has been proposed regarding brain ischemia. Phospholipase C is an enzyme that catalyzes the phosphodiesteratic cleavage of phosphatidylinositol. The cleavage of phosphatidylinositol 4,5-bisphosphate by phospholipase C yields 1,4,5-inositol triphosphate, which mediates intracellular release of calcium, and 1,2-diacylglycerol, which is an activator of protein kinase C. We examined the effect of phenylmethylsulfonyl fluoride, a phospholipase C inhibitor, on delayed neuronal damage after transient forebrain ischemia in the hippocampal CA1 subfield in rats to assess the role of phospholipase C in postischemic neuronal damage.

Twenty-minute forebrain ischemia was induced using the method of Pulsinelli and Brierley. We measured the neuronal density of the hippocampal CA1 subfield 7 days after reperfusion. The effect of phenylmethylsulfonyl fluoride was tested in both pretreatment and posttreatment groups.

In the vehicle treatment group (n = 13), neuronal density was 51 +/- 42/mm (mean +/- SD). The neuronal densities in the 50-mg/kg (n = 12) and 100-mg/kg (n = 14) phenylmethylsulfonyl fluoride pretreatment groups and the 100-mg/kg (n = 10) phenylmethylsulfonyl fluoride posttreatment group were 99 +/- 50, 150 +/- 55, and 143 +/- 63/mm, respectively. These values were significantly higher than that of the vehicle treatment group (p less than 0.05, p less than 0.01, and p less than 0.01, respectively).

It is suggested that the activation of phospholipase C has an important role in postischemic delayed neuronal damage.
Low and high density lipoprotein metabolism in atherothrombotic brain infarction.
Authors: Alam R , Yatsu F M , Kasturi R , Bui G
Published: June 2011

Elevated low density lipoprotein and reduced high density lipoprotein cholesterol may increase the risk of atherothrombotic brain infarction, but the metabolic mechanisms accounting for this relation are poorly understood.

The kinetic parameters of low density and high density lipoprotein were studied in nine subjects with atherothrombotic brain infarction or identifiable (by noninvasive testing) extracranial occlusive disease and in 12 control subjects. Autologous iodine-125-labeled lipoproteins were injected intravenously. Blood samples were drawn 10 minutes after injection and periodically thereafter for 10 days. Kinetic parameters were calculated from the decay curves.

The stroke-risk group showed significantly higher triglyceride (p less than 0.05), total cholesterol (p less than 0.02), and low density lipoprotein cholesterol (p less than 0.01). The fractional catabolic rate of low density lipoprotein was significantly lower (p less than 0.001) and the high density lipoprotein rate higher (p less than 0.02) in the stroke-risk group than in the control group. Regression analysis (using all subjects) of serum lipoproteins and their respective fractional catabolic rates correlated significantly (for low density lipoprotein, r = 0.684, p less than 0.001; for high density lipoprotein, r = 0.595, p less than 0.002). Mean percent stenosis showed a significant relation with triglyceride level (r = 0.678, p less than 0.01) and low density lipoprotein cholesterol (r = 0.535, p less than 0.02) but not with high density lipoprotein cholesterol. Mean percent stenosis also showed correlation with both fractional catabolic rate of low density lipoprotein (r = 0.667, p less than 0.002) and with serum high density lipoprotein levels (r = 0.504, p less than 0.02).

Our study provides insights into the role of altered low and high density lipoprotein metabolism in the pathogenesis of carotid stenosis. The statistically significant association of serum lipoprotein metabolic rates with carotid stenosis, rather than their respective serum concentrations, implies that metabolic parameters may be more important in predicting stroke risk.
Low blood-to-cerebrospinal fluid passage of sorbitol after intravenous infusion.
Authors: Nau R , Dreyhaupt T , Kolenda H , Prange H W
Published: June 2011

Compared with mannitol, the osmotherapeutic agent sorbitol is less prone to accumulate in the blood and the same quantity may be infused in a smaller volume. Because of these advantageous characteristics, we studied the pharmacokinetics of sorbitol in serum and cerebrospinal fluid.

Six patients (five women and one man; age range, 46-70 years) with an external ventriculostomy and suffering from brain edema due to cerebrovascular disease received sorbitol as part of their therapy. Before and after the first dose of 50 g infused over 20 minutes, sorbitol concentrations in serum and cerebrospinal fluid were determined repeatedly using an enzymatic procedure.

Maximal sorbitol concentrations ranged from 2,705 to 5,821 (median, 3,227) mg/l in serum compared with 6.7-130.7 (median, 19.5) mg/l in cerebrospinal fluid. Cerebrospinal fluid maxima were observed 0.17-3 hours after the end of the infusion. Sorbitol elimination in serum was adequately described by a two-compartment pharmacokinetic model (distribution half-life, 0.05-0.14 hour; elimination half-life, 0.23-0.61 hour). Elimination in cerebrospinal fluid followed a single-exponential decay and was considerably slower than that in serum (half-life, 1.3-7.7 hours).

The maximal cerebrospinal fluid concentration/maximal serum concentration ratio was low for sorbitol, thus suggesting a small potential risk of inducing an increase of intracranial pressure after osmotherapy (rebound effect).
A phenothiazine derivative reduces rat brain damage after global or focal ischemia.
Authors: Yu M J , McCowan J R , Smalstig E B , Bennett D R , Roush M E , Clemens J A
Published: June 2011

We previously reported that 2-(10H-phenothiazin-2-yloxy)-N,N-dimethylethanamine hydrochloride is a potent inhibitor of iron-dependent lipid peroxidation in vitro and can protect primary cultures of rat hippocampal neurons from hydrogen peroxide-induced toxicity. Because oxidants may play an important role in mediating postischemic tissue injury, we evaluated this agent in two rat models of transient cerebral ischemia.

In a model of global forebrain ischemia, 23 male Wistar rats were subjected to 10 minutes of four-vessel occlusion followed by 72 hours of reperfusion. The rats received three intraperitoneal injections of either vehicle (2% aqueous acacia) or test agent (40 mg/kg). In a model of focal stroke, 19 spontaneously hypertensive rats were subjected to 2 hours of tandem middle cerebral and ipsilateral common carotid artery occlusion followed by 24 hours of reperfusion. The rats received three intraperitoneal injections of either vehicle (2% aqueous acacia) or test agent (40 mg/kg).

In the global model, the phenothiazine significantly protected the CA1 layer of the hippocampus, with a reduction in mean damage score from 2.1 +/- 0.3 for control rats to 1.0 +/- 0.4 for treated rats (p less than 0.05). In the transient focal stroke model, the compound reduced cortical infarct volume from 130.1 +/- 10.3 mm3 for control rats to 95.2 +/- 24.5 mm3 for treated rats (p less than 0.02).

Although the primary mechanism responsible for the protective effect is unclear at the present time, our study is consistent with the hypothesis that oxidant-mediated lipid peroxidation may be involved in the pathophysiology of postischemic brain injury.
Neuroprotective mechanism of (+)SKF 10,047 in vitro and in gerbil global brain ischemia.
Authors: Lysko P G , Yue T L , Gu J L , Feuerstein G
Published: June 2011

The N-methyl-D-aspartate receptor is believed to mediate part of the ischemic neuronal damage caused by the excitatory amino acid glutamate. (+)SKF 10,047, the prototypic sigma-agonist, interacts with the N-methyl-D-aspartate receptor. Therefore, we studied the neuroprotective effect of (+)SKF 10,047 on cultured rat cerebellar neurons and on CA1 hippocampal neurons of gerbils exposed to brain ischemia.

Mechanisms of neuroprotection were studied in vitro by measuring calcium influx into cultured rat cerebellar granule cells loaded with fura 2-AM. In vivo neuroprotection of gerbil CA1 hippocampal neurons was studied in a posttreatment regimen following 5 minutes of bilateral carotid artery occlusion and 7 days of reperfusion.

In primary cultured rat cerebellar granule cell neurons, (+)SKF 10,047 in a dose-dependent manner diminished intracellular calcium levels of N-methyl-D-aspartate-stimulated neurons by a maximum of 87% (n = 8), with a 50% inhibitory concentration of 0.8 microM. (+)SKF 10,047 did not prevent subsequent calcium influx stimulated by kainic acid or KCl, nor did it interfere with modulation of the kainate response by quisqualic acid. Neuroprotection of 64% (p = 0.006, n = 15) of gerbil CA1 hippocampal neurons was achieved by posttreatment injection followed by minipump infusion.

Neuroprotection by (+)SKF 10,047 most likely involves interaction at the N-methyl-D-aspartate receptor. These results suggest that the benzomorphan class of sigma-agonists may provide neuroprotection in cerebral ischemia and stroke.
Multivariate prediction of the first major cerebrovascular event in an Italian population sample of middle-aged men followed up for 25 years.
Authors: Menotti A , Lanti M , Seccareccia F , Giampaoli S , Dima F
Published: June 2011

The present investigation was aimed at evaluating the incidence and prediction of a first major cerebrovascular (fatal or nonfatal) event.

The study population included the two Italian rural samples of the Seven Countries Study (namely, Montegiorgio and Crevalcore), accounting for a total of 1,712 men aged 40-59 years at entry and followed up for mortality and morbidity for 25 years. A number of individual variables measured at baseline, at the fifth year, and at the tenth year of follow-up and possibly related to cerebrovascular events were considered. Of the 1,709 subjects free from major cerebrovascular events at entry 171 developed a first major cerebrovascular event, but for the multivariate Cox model analysis only 1,572 subjects and 152 events were employed due to some exclusions for missing data.

Systolic blood pressure, indexes of respiratory function (protective), and physical activity at work (protective) demonstrated significant predictive roles for all ages and all lengths of follow-up considered. Other factors (presence of arrhythmias, presence of arcus senilis, and skinfold thickness [protective]), significantly contributed to the prediction, but in only some models. Time-related changes in systolic blood pressure significantly improved the prediction of cerebrovascular events.

The multivariate prediction performed in this report allowed the validation of three risk factors (systolic blood pressure, respiratory function indexes, and physical activity at work) whose predictive powers remain stable with aging. The need for further studies specifically aimed at discriminating hemorrhagic from thrombotic events is suggested.
Amplitude of the ocular pneumoplethysmography waveform is correlated with cardiac output.
Authors: Bosley T M , Cohen M S , Gee W , Reed J , Sergott R C , Savino P J
Published: June 2011

Ocular pulse amplitude, the amplitude of the ocular pneumoplethysmographic waveform, is altered in several ophthalmologic diseases that disturb ocular blood flow, implying that ocular pulse amplitude may provide an estimate of ocular blood flow. Because ocular blood flow currently cannot be quantified in humans, two experiments were undertaken to evaluate the association of ocular pulse amplitude with total body blood flow.

In experiment 1, cardiac output was determined by cardiac catheterization in 181 patients who underwent OPG-Gee testing during the same hospitalization. In experiment 2, 110 instances of atrial arrhythmia captured on ocular pneumoplethysmographic tracings were evaluated for transient changes in heart rate (R-R ratio) associated with transient changes in ocular pulse amplitude (ocular pulse amplitude ratio).

In experiment 1, average ocular pulse amplitude in the two eyes (OPAAV) was significantly correlated with cardiac output/heart rate (r = 0.53; p < 0.0001) and cardiac index/heart rate (r = 0.43; p < 0.0001). In experiment 2, R-R ratio was significantly correlated with ocular pulse amplitude ratio (r = 0.85; p < 0.001).

These results show that ocular pulse amplitude, a physiological measurement obtained from the globe, is correlated with cardiac output. They imply that ocular pulse amplitude may provide a clinically useful estimate of at least the pulsatile component of ocular blood flow.
Frequency and prognosis of stroke/TIA among 4808 survivors of acute myocardial infarction. The SPRINT Study Group.
Authors: Tanne D , Goldbourt U , Zion M , Reicher-Reiss H , Kaplinsky E , Behar S
Published: June 2011

Stroke complicating acute myocardial infarction is associated with substantial morbidity and mortality. The purpose of this study was to assess the incidence, predictors, and impact on mortality of stroke/transient ischemic attacks occurring after hospital discharge in a large unselected population of acute myocardial infarction survivors.

During a secondary prevention study with nifedipine (SPRINT), demographic, anamnestic, and clinical data were collected for 5839 consecutive acute myocardial infarction patients admitted to 13 coronary care units in Israel. Hospital survivors (n = 4808) were followed for a year after their discharge. Mortality was assessed for a mean follow-up of 5.5 years (range, 4.5 to 7 years).

One percent (48/4808) of hospital survivors from acute myocardial infarction experienced a stroke/transient ischemic attack in the year after acute myocardial infarction. Thirty-one percent (15 of 48) of events occurred in the first month after hospital discharge. Incidence was higher among older patients (> 70 years; 1.9%), those with anterior site of myocardial infarction (1.35%), a previous history of myocardial infarction (1.8%), hypertension (1.4%), stroke in the past (4.1%), and chronic atrial fibrillation (9%). Multivariate analysis identified the following as independent predictors of stroke/transient ischemic attacks occurring in the year after hospital discharge: chronic atrial fibrillation, older age, history of previous myocardial infarction, anterior myocardial infarction site, serum glutamic oxaloacetic transaminase levels more than four times above upper normal limits, and stroke in the past. The age-adjusted 1-year and long-term mortality rates (4.5 to 7 years; mean, 5.5 years) were significantly higher in patients with (31% and 62%) than in those without stroke/transient ischemic attacks (9% and 31%, respectively; P < .01).

Stroke/transient ischemic attack is a relatively rare (1%) complication in the year after hospital discharge from acute myocardial infarction, though more frequent in the first month. Chronic atrial fibrillation, older age, anterior myocardial infarction site, serum glutamic oxaloacetic transaminase levels more than four times above upper normal limits, past myocardial infarction, and stroke identify high-risk patients. Patients suffering from subsequent stroke/transient ischemic attacks experienced higher mortality than counterparts who remained free from this complication.
Changes in glucose utilization in the rat brain after transient forebrain ischemia.
Authors: Kozuka M , Kobayashi K , Iwata N
Published: June 2011

Although several local cerebral glucose utilization (LCGU) studies using rat forebrain ischemia models have been performed to date, none that investigate long-term postischemic changes in LCGU throughout the brain have been reported. We investigated postischemic changes throughout the brain over 14 days using a rat forebrain ischemia model.

Cerebral ischemia was produced using the rat four-vessel occlusion model. After 30 minutes of ischemia cerebral blood flow was restored, and LCGU in 34 structures in the brain was evaluated at 1, 3, 5, 7, and 14 days after ischemia.

LCGU changes were characterized and could be divided into two major patterns, type 1 and type 2. In type 1, LCGU was reduced remarkably at 1 and 3 days, and it returned to near the control level at 5 days. In type 2, LCGU was reduced mildly at 1 day and returned to near the control level at 3 days. Included in type 1 were the severely ischemic structures such as the cerebral cortices and striatum. Included in type 2 were the less severely ischemic structures such as the midbrain, cerebellum, and pons and medulla oblongata. Drastic changes in LCGU took place not only in gray matter but also in white matter, and the patterns of LCGU changes were similar in both regions. Atypical changes in LCGU were observed in the hippocampal CA1 and substantia nigra pars reticulata. In both structures, LCGU was remarkably increased around 7 days after ischemia.

There are two major patterns of LCGU changes after transient forebrain ischemia. LCGU changes in the hippocampal CA1 and substantia nigra pars reticulata are atypical.
Endothelial modulation of contractions caused by oxyhemoglobin and NG-nitro-L-arginine in isolated dog and monkey cerebral arteries.
Authors: Toda N , Ayajiki K , Okamura T
Published: June 2011

Oxyhemoglobin is a key substance in provoking cerebral vasospasm and a scavenger of nitric oxide. The present study was designed to determine whether suppression of the action of endothelium-derived nitric oxide is involved in oxyhemoglobin-induced cerebroarterial contraction.

Dog and monkey cerebral artery strips with and without endothelium were immersed for isometric tension recording in modified Ringer-Locke solution aerated with 95% oxygen and 5% carbon dioxide.

NG-nitro-L-arginine, a nitric oxide synthase inhibitor, produced concentration-related contraction that was greater in the strips with intact endothelium than in those denuded of endothelium. The D-enantiomer caused no or only a slight contraction. In the presence of NG-nitro-L-arginine, oxyhemoglobin elicited additional contraction that is comparable to or even greater than that obtained in the absence of the inhibitor. The oxyhemoglobin-induced contraction was attenuated by endothelium denudation.

Inhibition of the basal release of nitric oxide from endothelium results in dog and monkey cerebral arterial contraction. However, the inhibition of nitric oxide action is not a major mechanism involved in oxyhemoglobin-induced contraction; other mechanisms, such as the release of prostanoids, appear to be important.