bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of low-to-high doses of aspirin on platelet aggregability and metabolites of thromboxane A2 and prostacyclin.
Authors: Tohgi H , Konno S , Tamura K , Kimura B , Kawano K
Published: June 2011

The purpose of this study was to compare the effects of low-to-high doses of aspirin on platelet aggregability determined by different methods and on the metabolism of thromboxane A2 and prostacyclin.

We administered increasing doses (40, 320, and 1,280 mg/day) of aspirin to 19 poststroke patients and studied the differences in 1) the changes in platelet aggregability depending on the methods of evaluation and 2) the concentrations of prostaglandin metabolites in the blood and urine.

Aggregation of platelet-rich plasma induced by a strong stimulus (10 microM ADP) was significantly reduced after 40 mg/day aspirin (p less than 0.005), and this reduction was similar to that after higher aspirin doses. In contrast, aggregation of platelet-rich plasma induced by weaker stimuli (1 and 5 microM ADP) decreased less significantly after 40 mg/day aspirin compared with that after higher aspirin doses. The serum thromboxane B2 generated after ex vivo incubation was reduced significantly (by 85%) after 40 mg/day aspirin and decreased further after 320 mg/day (by 96%) and 1,280 mg/day (by greater than 99%) of aspirin. The urinary 11-dehydro-thromboxane B2 concentration decreased less significantly after 40 mg/day aspirin (by 42%) compared with that after 320 mg/day (by 78%) and 1,280 mg/day (by 91%) aspirin doses. The urinary concentration of 2,3-dinor-6-keto-prostaglandin F1 alpha did not decrease after 40 mg/day aspirin but decreased significantly after higher doses of aspirin.

These findings suggest that different doses of aspirin may be necessary to prevent thrombogenesis induced by different triggers of different strengths and that 40 mg/day aspirin is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.
Endothelium-derived relaxing factor in brain blood vessels is not nitric oxide.
Authors: Rosenblum W I
Published: June 2011

The endothelium-derived relaxing factor that mediates the actions of acetylcholine is now most frequently identified as nitric oxide. Nitric oxide is believed to have numerous important regulating actions in neurons, blood vessels, and several other biological systems.

The literature concerning tissue other than cerebral blood vessels supports the conclusion that the endothelium-derived relaxing factor for acetylcholine is either nitric oxide or a compound formed from and containing nitric oxide (for example, a nitrosothiol). However, papers can be found indicating that this endothelium-derived mediator is not nitric oxide. In brain blood vessels the evidence is strongly against the conclusion that nitric oxide is the endothelium-derived mediator for acetylcholine. If this mediator is formed from nitric oxide, either in brain vessels or in other vessels, no data are available delineating how this synthesis is regulated or whether and where nitric oxide leaves the nitroso compound to initiate dilation. Indeed, cerebrovascular data now cast doubt on the commonly held belief that nitrosovasodilators regulate vascular tone by giving off nitric oxide to vascular smooth muscle.

In brain blood vessels the chemical identity of the endothelium-derived relaxing factor mediating the action of acetylcholine is unknown, but this relaxing factor does not appear to be nitric oxide. If the mediator contains nitric oxide, as is probably the case, the means by which it activates vascular guanylate cyclase and/or produces dilation is unknown. Since this relaxing factor inhibits platelet adhesion/aggregation in cerebral vessels as well as relaxing these vessels, the chemical identification of this relaxing factor and the elucidation of its mode of action are extremely important to our understanding and control of cerebrovascular phenomena in health and disease.
Lipoprotein and apolipoprotein profile in men with ischemic stroke. Role of lipoprotein(a), triglyceride-rich lipoproteins, and apolipoprotein E polymorphism.
Authors: Pedro-Botet J , Sentí M , Nogués X , Rubiés-Prat J , Roquer J , D'Olhaberriague L , Olivé J
Published: June 2011

The role of lipoprotein abnormalities in the development of ischemic cerebrovascular disease has not been sufficiently clarified. The aim of this study was to identify the lipoprotein profile in ischemic cerebrovascular disease and the possible role of apolipoprotein E polymorphism.

The relation between the concentrations of lipoprotein(a), intermediate density lipoproteins, apolipoprotein A-I, apolipoprotein B, apolipoprotein E, and other lipoproteins was studied in 100 men with ischemic cerebrovascular disease (48 atherothrombotic, 28 lacunar, and 24 of unknown type) and in 100 healthy age-matched men as a control group.

Patients with ischemic cerebrovascular disease had significantly higher levels of lipoprotein(a), lipids carried by intermediate density lipoproteins, and low density lipoprotein cholesterol and lower levels of high density lipoproteins than control subjects. Patients with atherothrombotic infarction had higher total serum cholesterol and low density lipoprotein cholesterol concentrations than patients with lacunar infarction. To assess lipoprotein abnormalities in normolipidemic subjects, a subgroup of 38 patients with ischemic cerebrovascular disease and 53 control subjects, both with serum cholesterol levels < 5.2 mmol/l (200 mg/dl) and triglycerides < 2.3 mmol/l (200 mg/dl), was analyzed. Serum lipoprotein(a), lipids carried by very low density lipoproteins and intermediate density lipoproteins, and low density lipoprotein triglycerides were significantly higher in normolipidemic patients compared with normolipidemic control subjects, whereas high density lipoprotein cholesterol levels were lower. Apolipoprotein E polymorphism in our ischemic cerebrovascular patients differed from that of the control group, with the epsilon 4 allele being more prevalent.

Increased serum lipoprotein(a) levels and intermediate density lipoprotein abnormalities together with decreased high density lipoprotein levels are major risk factors for ischemic cerebrovascular disease, even in normocholesterolemic and normotriglyceridemic subjects. Finally, the epsilon 4 allele could probably be a predisposing genetic marker for ischemic cerebrovascular disease.
Cerebral cysticercosis as a risk factor for stroke in young and middle-aged people.
Authors: Alarcón F , Vanormelingen K , Moncayo J , Viñán I
Published: June 2011

A probable association between cerebral cysticercosis and susceptibility to stroke, especially among young and middle-aged patients, has been reported. We examined the association between cerebral cysticercosis and stroke and the possible factors causing this association.

In 169 stroke patients (75 males and 94 females) under 65 years of age admitted to our neurology department, we evaluated the following possible risk factors: arterial hypertension, diabetes, cardiac disease, hyperlipidemia, smoking, alcohol abuse, and cerebral cysticercosis. In 169 control patients under 65 years of age matched by sex and age, we evaluated the same possible risk factors for stroke.

In the univariate matched analyses, the frequencies of cerebral cysticercosis (p < 0.001), arterial hypertension (p < 0.001), cardiac disease (p < 0.001), hyperlipidemia (p < 0.05), and alcohol abuse (p = 0.05) were higher in the stroke patients than in the control patients. After controlling for possible confounding factors, we found that arterial hypertension (p < 0.001), cardiac disease (p < 0.001), and cerebral cysticercosis (p < 0.001) were independent risk factors for stroke.

Cerebral cysticercosis should be considered a risk factor for stroke in young and middle-aged individuals.
Prediction of cerebral ischemia by ophthalmoscopy after carotid occlusion in gerbils.
Authors: Oostveen J A , Timby K , Williams L R
Published: June 2011

The Mongolian gerbil provides a unique model of unilateral focal cerebral ischemia because of the lack of posterior communicating arteries in all gerbils as well as an absence of an anterior communicating artery in approximately 20% of the gerbil population. It is unclear how to identify unequivocably the subpopulation of animals that would suffer a severe focal cerebral ischemia after unilateral carotid occlusion.

Ninety-three male gerbils were exposed to unilateral occlusion of the right common carotid artery. The severity of neuronal loss was evaluated histologically in gerbils selected as having significant focal ischemia based on either behavioral criteria (i.e., the demonstration of stereotypical behavior within 1 hour after occlusion) or ophthalmoscopic criteria (i.e., interruption of the retinal arterial perfusion within 10 minutes of carotid ligation as assessed with an ophthalmoscope). After 3 hours of unilateral carotid occlusion, cerebral blood flow was reinstated for 24 hours before fixation for histological analysis. The viability of the CA1 region of the hippocampus, lateral cortex, and medial cortex was scored on a scale of 0-4 based on the percentage of apparent neuronal loss (e.g., 0, no damage; 4, > 75% damage (the Viability Index).

Twenty-eight percent of the gerbils met the behavioral selection criteria, and 17% met the ophthalmoscopic criteria. In the specimens selected by behavioral criteria (n = 7), 30% demonstrated no evidence of postischemic neuronal loss; the mean +/- SEM Viability Index scores for CA1, lateral cortex, and medial cortex were 1.6 +/- 0.6, 1.0 +/- 0.3, and 0.3 +/- 0.2, respectively. Of the animals selected by ophthalmoscopic criteria (n = 12), 100% had severe ischemic tissue damage to the ipsilateral hemisphere; the Viability Index scores for CA1, lateral cortex, and medial cortex were 3.5 +/- 0.1, 3.1 +/- 0.2, and 1.2 +/- 0.2, respectively; all scores were significantly larger than those observed in the behaviorally selected group.

Selection of animals by ophthalmoscopic criteria provides a reliable, consistent method to predict animals with severe focal cerebral ischemia.
Effects of nicardipine on tube formation of bovine vascular endothelial cells in vitro.
Authors: Kaneko T , Nagata I , Miyamoto S , Kubo H , Kikuchi H , Fujisato T , Ikada Y
Published: June 2011

The purpose of this study was to assess the effect of nicardipine, a Ca2+ channel blocker, on angiogenesis in vitro.

Bovine carotid artery endothelial cells were cultured between type I collagen gel layers with 10(-9) to 10(-5) M nicardipine. The morphological changes were monitored by phase-contrast microscopy and photographed. The total length of tubular structures was measured with an image analyzer system. Endothelial proliferation and migration assays were also performed with the same doses of nicardipine.

Cultured endothelial cells form tubular structures between collagen gel layers. Tube formation of endothelial cells was suppressed by culture with 10(-9) to 10(-5) M nicardipine in a dose-dependent manner. Migration of endothelial cells was also suppressed by the same doses of nicardipine. However, proliferation of endothelial cells was not enhanced.

Nicardipine acts as an inhibitor of angiogenesis in vitro by inhibiting the migration of endothelial cells. This result suggests that nicardipine may have therapeutic potential in angiogenic disorders such as tumor growth, atherogenesis, and diabetic retinopathy.
Prevalence and determinants of carotid atherosclerosis in a general population.
Authors: Prati P , Vanuzzo D , Casaroli M , Di Chiara A , De Biasi F , Feruglio G A , Touboul P J
Published: June 2011

The aim of this study was to assess the prevalence of asymptomatic carotid atherosclerotic lesions and their relation to principal risk factors. The importance of the relation between asymptomatic carotid atherosclerotic lesions, stroke, and coronary atherosclerosis has been widely discussed, but there are few transversal and longitudinal studies on a general population.

A noninvasive examination was carried out using high-resolution B-mode ultrasonography, which has been shown to be a reliable tool for epidemiological studies. We examined 630 men and 718 women aged 18-99 years (participation rate, 74.9%).

The global prevalence of carotid atherosclerosis was 25.4% in men and 26.4% in women. Intimal-medial thickening was found in 9.4% of men and 11.7% of women. Plaque prevalence was 13.3% in men and 13.4% in women; prevalence of stenotic plaques was 2.7% and 1.5%, respectively. Subjects aged < or = 39 years showed a very low prevalence of any asymptomatic carotid atherosclerotic lesions. In the multiple logistic regression, the analysis of subjects aged > or = 40 years showed a positive significant association between the severity of carotid atherosclerotic lesions (plaques and stenosis) and age (p < 0.001), systolic blood pressure (p < 0.01), cigarette smoking (p < 0.0001), and the protective effect of high density lipoprotein cholesterol (p < 0.037). This analysis did not provide evidence of a clear-cut association between risk factors and intimal-medial thickening.

This population study shows the high prevalence of asymptomatic carotid atherosclerotic lesions in a general population (approximately 25% of adults) and its relation with the classic risk factors. It emphasizes the value of ultrasonography in the detection of early atherosclerotic lesions.
Insulin-induced normoglycemia improves ischemic outcome in hyperglycemic rats.
Authors: Warner D S , Gionet T X , Todd M M , McAllister A M
Published: June 2011

Hyperglycemia is known to aggravate ischemic brain damage. This study sought to determine if preischemic insulin-induced normoglycemia would improve outcome in hyperglycemic rats.

Normal rats and rats with 5-7 days of streptozotocin-induced diabetes were studied. Normal rats served as either fasted normoglycemic controls or dextrose-infused (hyperglycemic) controls. In the acutely diabetic rats either no insulin was given or insulin was given at 30 or 90 minutes before ischemia so as to induce preischemic normoglycemia. All rats underwent 10 minutes of forebrain ischemia. After 5 days of recovery, motor function and histological outcome were assessed.

Untreated diabetic rats and dextrose-infused control rats had greater hippocampal CA1 damage than normoglycemic control rats. In contrast, insulin-treated diabetic rats had less hippocampal CA1 damage than either untreated diabetic rats or dextrose-infused control rats. Injury in the two insulin-treated groups was not significantly different from that in the normoglycemic control group (all three groups had plasma glucose values of 120-150 mg/dl immediately prior to ischemia). Despite similar plasma glucose values (300-400 mg/dl), fewer postischemic seizures (0% versus 67%) were observed in the untreated diabetic group than in the dextrose-infused control group (p < 0.001).

Hyperglycemia caused by either dextrose infusion or streptozotocin-induced diabetes resulted in exacerbated ischemic brain damage. Insulin therapy to rapidly induce preischemic normoglycemia improved outcome from forebrain ischemia in the acutely diabetic rats. Glucose-infused hyperglycemic rats frequently exhibited postischemic generalized seizures while acutely diabetic rats did not. The latter results implicate some adaptive/protective mechanism associated with acute streptozotocin-induced diabetes that results in a decreased sensitivity to hyperglycemia-augmented ischemic brain damage.
Course of carotid artery occlusions with impaired cerebrovascular reactivity.
Authors: Kleiser B , Widder B
Published: June 2011

Retrospective studies have found a close correlation between an impaired cerebrovascular reserve capacity and the incidence of hemodynamic stroke. The present study evaluates this relation prospectively.

We measured the CO2 reactivity in 85 patients with internal carotid artery occlusions by transcranial Doppler sonography (Doppler CO2 test). All patients were prospectively followed for 38 +/- 15 (mean +/- SD) months.

In the group with sufficient CO2 reactivity, four of 48 (8%) developed ipsilateral transient symptoms, none a stroke. In cases with diminished or exhausted cerebrovascular reserve capacity, 12 of 37 (32%) suffered an ipsilateral event (four transient ischemic attacks, eight strokes) (p less than 0.01).

The Doppler CO2 test seems to be a valuable method of estimating the risk of stroke in patients with carotid artery occlusions.
Markers of a hypercoagulable state following acute ischemic stroke.
Authors: Takano K , Yamaguchi T , Uchida K
Published: June 2011

The nature of hematologic disorders in different stroke subtypes remains uncertain. The purpose of this study was to clarify the differences in the coagulation and fibrinolytic activities among ischemic stroke subtypes.

We performed sequential measurements of hematologic parameters in 21 patients with acute cardioembolic stroke, 10 patients with atherothrombotic stroke, 23 patients with lacunar stroke, and 20 age-matched controls.

A marked elevation of plasma concentrations of the thrombin-antithrombin III complex and crosslinked D-dimer was observed only in cardioembolic stroke within 48 hours of onset (p less than 0.01), persisting for one month with a gradual decline. In atherothrombotic stroke, however, the level of crosslinked D-dimer was not elevated at the onset, but increased seven days after onset (p less than 0.01). No significant changes in these marker levels were observed in lacunar stroke.

Our findings suggest that the nature of altered coagulation and fibrinolysis are different in various subtypes of ischemic stroke, and that an assessment of these hematologic parameters may be useful for the early classification of these subtypes.
Effect of flunarizine on electroencephalogram recovery and brain temperature in gerbils after brain ischemia.
Authors: Cohan S L , Redmond D , Chen M
Published: June 2011

This study was designed to determine whether flunarizine enhances the rate of brain recovery as measured by electroencephalography after cerebral ischemia and whether these effects are attributable to changes in brain temperature.

Male gerbils (n = 81) were treated with either 10 mg/kg flunarizine or its vehicle, beta-cyclodextrin, intraperitoneally, 60 minutes before bilateral carotid occlusion of either 4 or 6 minutes' duration. The electroencephalogram was continuously recorded in the preischemic, ischemic, and postischemic stages of the experiment and rated for the time necessary for the return of 4-6, 7-10, and 11-15 Hz activity. In a second set of experiments, intracerebral temperature was monitored for 60 minutes before ischemia, during 10 minutes of carotid occlusion, and for 60 minutes after ischemia.

Flunarizine pretreatment resulted in significantly more rapid return of electroencephalographic activity in each of the three frequency categories monitored when compared with those animals pretreated with vehicle alone (p less than 0.001). Flunarizine had no effect on brain temperature before, during, or up to 60 minutes after termination of ischemia.

Flunarizine, which has been of efficacy in reducing neuronal death, mortality, and functional impairment when administered after ischemic insults, may have prophylactic value in accelerating brain recovery from ischemia, but does not have this effect as a result of altered brain temperature.
Comparison of magnetic resonance angiography, conventional angiography, and duplex scanning.
Authors: Riles T S , Eidelman E M , Litt A W , Pinto R S , Oldford F , Schwartzenberg G W
Published: June 2011

To determine the accuracy of magnetic resonance angiography in assessing patients with cerebrovascular disease, we performed a study comparing the results of conventional cerebral angiography, duplex scanning, and magnetic resonance angiography.

From 42 patients, a total of 25 carotid arteries were evaluated by all three techniques. The studies were independently read and sorted into five categories according to the degree of stenosis: 0-15%, normal; 16-49%, mild; 50-79%, moderate; 80-99%, severe; and totally occluded.

Magnetic resonance angiography correlated exactly with conventional angiography in 39 arteries (52%); duplex scanning correlated with conventional angiography in 49 cases (65%). Compared with conventional angiography, both magnetic resonance angiography and duplex scanning tended to overread the degree of stenosis. The most critical errors associated with magnetic resonance angiography were three readings of total occlusion in vessels found to be patent on conventional angiograms.

Although magnetic resonance angiography offers great hope of providing high-quality imaging of the carotid artery with no risk and at less cost, data from this study suggest that misreading the degree of stenosis, or misinterpreting a stenosis for an occlusion, could lead to errors in clinical decisions. Guidelines for use of magnetic resonance angiography in a clinical setting are offered.
Stroke registry in Malmö, Sweden.
Authors: Jerntorp P , Berglund G
Published: June 2011

A stroke registry covering the city of Malmö, Sweden (population 232,000) was started in January of 1989 to prospectively follow up stroke incidence, recurrence, and fatality rates.

Patients with presumed stroke were interviewed within 1 week after admission to the hospital, and their medical records were examined. Continuous validation against hospital diagnosis showed well over 90% of all stroke cases in Malmö to have been included.

Incidence rates per 100,000 residents were 300 for all stroke events and 225 for first-ever stroke, lower than those reported from other studies. The distribution of stroke diagnostic categories was 3% subarachnoid hemorrhage, 10% intracerebral hemorrhage, 50% cerebral infarction, and 38% unspecified stroke. The diagnosis was based on computed tomography in 51% of first-ever stroke cases. Median age was 73.1 years for men and 79.7 years for women. Incidence rates for all stroke diagnostic categories except subarachnoid hemorrhage increased with age. Prior stroke, hypertension, smoking, atrial fibrillation, and diabetes mellitus were major risk factors for all stroke events. The presenting symptoms were hemiparesis in 74%, speech disorder in 49%, and clouded consciousness in 19% of the patients. The overall case-fatality rate at 30 days was 15%; the rate for intracerebral hemorrhage was 37% and that for cerebral infarction was 10%.

Our findings confirm the value of a stroke registry for stroke epidemiology purposes and as a tool for specific stroke research.
The onset of postischemic hypoperfusion in rats is precipitous and may be controlled by local neurons.
Authors: Frerichs K U , Sirén A L , Feuerstein G Z , Hallenbeck J M
Published: June 2011

Reperfusion following transient global cerebral ischemia is characterized by an initial hyperemic phase, which precedes hypoperfusion. The pathogenesis of these flow derangements remains obscure. Our study investigates the dynamics of postischemic cerebral blood flow changes, with particular attention to the role of local neurons.

We assessed local cortical blood flow continuously by laser Doppler flowmetry to permit observation of any rapid flow changes after forebrain ischemia induced by four-vessel occlusion for 20 minutes in rats. To investigate the role of local cortical neurons in the regulation of any blood flow fluctuations, five rats received intracortical microinjections of a neurotoxin (10 micrograms ibotenic acid in 1 microliter; 1.5-mm-depth parietal cortex) 24 hours before ischemia to induce selective and localized neuronal depletion in an area corresponding to the sample volume of the laser Doppler probe (1 mm3). Local cerebral blood flow was measured within the injection site and at an adjacent control site.

Ischemia was followed by marked hyperemia (235 +/- 23% of control, n = 7), followed by secondary hypoperfusion (45 +/- 3% of control, n = 7). The transition from hyperemia to hypoperfusion occurred not gradually but precipitously (maximal slope of flow decay: 66 +/- 6%/min; n = 7). In ibotenic acid-injected rats, hyperemia was preserved at the injection site, but the sudden decline of blood flow was abolished (maximal slope of flow decay: 5 +/- 3%/min compared with 53 +/- 8%/min at the control site; n = 5, p less than 0.001) and no significant hypoperfusion developed (103 +/- 20% of control at 60 minutes).

These data suggest that the rapid transition to cortical hypoperfusion after forebrain ischemia may be triggered locally by a neuronal mechanism but that this mechanism does not underlie the initial hyperemia.
Concurrent myocardial and cerebral infarctions after intranasal cocaine use.
Authors: Sloan M A , Mattioni T A
Published: June 2011

Cardiac and cerebrovascular complications associated with cocaine abuse have increasingly been reported, but concurrent development of cocaine-induced cardiac disease and stroke has rarely been reported.

A 37-year-old man with a remote history of intravenous heroin and amphetamine use, cardiomyopathy, and recent cocaine use developed chest pain and ventricular tachycardia 30 minutes after intranasal cocaine hydrochloride use and jogging on a cold winter morning. Ventricular tachycardia was converted to atrial fibrillation. He was proven to have a small myocardial infarction. Within 6 hours of cocaine use he suffered a left hemisphere stroke. Cardiac electrophysiologic evaluation revealed inducible ventricular tachycardia.

To our knowledge, this is the first report of concurrent myocardial infarction, life-threatening ventricular arrhythmias, and cerebral infarction temporally related to cocaine use. It is probable that one mechanism by which cocaine use causes stroke is to trigger expression of a known cardiac source of embolism.
Improved prognosis for asymptomatic carotid stenosis with prophylactic carotid endarterectomy.
Authors: Freischlag J A , Hanna D , Moore W S
Published: June 2011

The value of carotid endarterectomy in asymptomatic patients with high-grade stenosis is controversial. The objective of this study is to compare the immediate and long-term outcome of patients after carotid endarterectomy for asymptomatic carotid stenosis (greater than 75%) with the reported natural history of patients followed nonoperatively to determine whether carotid endarterectomy reduces the subsequent neurological event rate.

The data from 141 carotid endarterectomies performed in 123 patients between January 1980 and December 1986 were reviewed from the perspective of perioperative results and long-term follow-up to January 1990, providing a follow-up ranging from 3 to 10 years. The mean follow-up was 56.6 months (range 27-117 months).

There were no perioperative deaths. There were two postoperative stokes: one in the cerebellar distribution and one in the middle cerebral distribution. During the course of follow-up, no patient suffered a stroke in the hemisphere ipsilateral to carotid endarterectomy. One patient developed ipsilateral transient ischemic attacks 24 months after surgery associated with carotid restenosis. A total of three patients developed four recurrent carotid stenoses, for an incidence of 2.8%. All four recurrences were corrected surgically.

These findings are in marked contrast to the reported natural history of patients with greater than 75% stenosis in which the 1-year neurological event rate is 18% and the 1-year stroke rate is 5%. Although final proof of efficacy for prophylactic carotid endarterectomy in asymptomatic patients will await the outcome of randomized trials, until these data are available, prophylactic carotid endarterectomy is justified in centers of excellence that can perform the surgery with low perioperative risk.
T2- and diffusion-weighted magnetic resonance imaging of a focal ischemic lesion in rat brain.
Authors: van Bruggen N , Cullen B M , King M D , Doran M , Williams S R , Gadian D G , Cremer J E
Published: June 2011

We sought to evaluate the application of T2-weighted and diffusion-weighted magnetic resonance imaging techniques in the study of a focal ischemic lesion in the rat brain.

Unilateral cortical infarcts were induced using the photosensitive dye rose bengal and 560 nm light irradiation. Magnetic resonance images were recorded from a total of 11 rats at selected intervals from 1.5 hours to several days after induction of the lesion. Parallel experiments were performed in which Evans blue dye was injected into the lesioned animals either immediately after lesion induction (n = 11) or 1 hour before the animals were killed (n = 11). The second procedure was designed to show regions of blood-brain barrier permeability to plasma proteins at the time of sacrifice, whereas the first procedure showed the accumulation and subsequent dispersion of plasma protein following disruption of the blood-brain barrier.

Regions of the cortex highlighted by the T2-weighted images corresponded well to the pattern of dye staining seen from the first procedure while the diffusion-weighted images showed visual correspondence with the staining pattern obtained using the second procedure.

These results illustrate the complementary use of T2-weighted and diffusion-weighted magnetic resonance imaging in discerning the pathophysiology of developing lesions.
Mild hypothermia reduces infarct size resulting from temporary but not permanent focal ischemia in rats.
Authors: Ridenour T R , Warner D S , Todd M M , McAllister A C
Published: June 2011

Mild hypothermia (32-35 degrees C) has been repeatedly shown in laboratory models to reduce damage resulting from global cerebral ischemic insults. Little information is available, however, regarding the protective potential of mild hypothermia against focal ischemia. We designed the present study to determine whether mild hypothermia influences outcome from either temporary or permanent middle cerebral artery occlusion in the rat.

In experiment 1 (permanent occlusion), mechanically ventilated, halothane-anesthetized spontaneously hypertensive rats underwent permanent ligation of the middle cerebral artery. Pericranial temperature was maintained at either 37 degrees C (n = 11) or 33 degrees C (n = 11) during the first 2 hours of occlusion. In experiment 2 (temporary occlusion), the vessel was occluded for 1 hour only. Pericranial temperature was controlled at either 37 degrees C (n = 12) or 33 degrees C (n = 14) during ischemia and for 1 hour after reperfusion. In both experiments, the rats were allowed to recover, with neurological function scored at 24 and 96 hours after onset of ischemia. Cerebral infarct volume (as determined by nitro blue tetrazolium staining) was planimetrically evaluated 96 hours after onset of ischemia.

No difference in infarct volume was observed between groups undergoing permanent occlusion (177 +/- 53 mm3 for 37 degrees C rats, 167 +/- 71 mm3 for 33 degrees C rats [mean +/- SD]). Although neurologic function correlated with infarct volume at 96 hours (all animals in experiment 1 combined; p less than 0.01), we were unable to demonstrate an intergroup difference in function. In animals undergoing temporary occlusion, mean +/- SD infarct volume was 48% less in the hypothermic group (89 +/- 54 mm3 for 37 degrees C, 46 +/- 31 mm3 for 33 degrees C; p less than 0.03). Neurological function again correlated with infarct size (p less than 0.02), but improvement in function approached significance for the hypothermic group (p less than 0.06) at 24 hours after reperfusion only.

Benefits from mild hypothermia may be obtained under conditions of temporary but not permanent middle cerebral artery occlusion in the rat.
Mechanism of detection of acute cerebral ischemia in rats by diffusion-weighted magnetic resonance microscopy.
Authors: Benveniste H , Hedlund L W , Johnson G A
Published: June 2011

The aim of this study was to measure apparent diffusion coefficients in rat brain tissue exposed to ouabain, glutamate, and N-methyl-D-aspartate and to compare them with apparent diffusion coefficients found in acute cerebral ischemia.

The apparent diffusion coefficient was measured using magnetic resonance microscopy in four groups of Sprague-Dawley rats after occlusion of the right middle cerebral artery and ipsilateral common carotid artery (n = 7), after ouabain exposure (n = 6), during glutamate exposure (n = 7), or during N-methyl-D-aspartate exposure (n = 3). Ouabain, glutamate, and N-methyl-D-aspartate were applied via an intracerebrally implanted microdialysis membrane.

Three hours after the induction of focal cerebral ischemia, a 33% reduction in the apparent diffusion coefficient was observed in the right dorsolateral corpus striatum and olfactory cortex. After ouabain exposure, reductions in the apparent diffusion coefficient were observed within a 1,500-microns radius of the microdialysis membrane. Quantitative analysis revealed that apparent diffusion coefficient values in ischemic and ouabain-exposed tissue fell within the same range. Glutamate and N-methyl-D-aspartate reduced the brain tissue apparent diffusion coefficient by 35% and 40%, respectively.

On the basis of these findings, we conclude that ischemia-induced apparent diffusion coefficient reductions are likely caused by a shift of extracellular to intracellular water.
Prevalence and etiology of dementia in a Japanese community.
Authors: Ueda K , Kawano H , Hasuo Y , Fujishima M
Published: June 2011

We sought to determine the type-specific prevalence of dementia and its risk factors in elderly persons from the Japanese community of Hisayama.

We studied the prevalence of dementia in 887 Hisayama residents (353 men and 534 women) aged 65 years or older (screening rate, 94.6%) using various items of clinical information, neurological examination, and dementia scales. We also studied brain morphology in 50 of 59 determined to have dementia by computed tomography or autopsy during the subsequent 54-month period. Factors relevant to dementia were compared between 27 patients with vascular dementia and 789 control subjects without dementia in a retrospective fashion.

The prevalence rate of dementia among Hisayama residents aged 65 or older was estimated at 6.7%, with a females to males ratio of 1:2. Among 50 cases of dementia in which brain morphology was examined, the frequency of vascular dementia was 56%; this rate was 2.2 times higher than that for senile dementia of the Alzheimer type. Aging, hypertension, electrocardiographic abnormalities, and high hematocrit were significantly (p less than 0.05) and independently associated with the occurrence of vascular dementia.

Prevalence of dementia among the Hisayama residents was relatively identical to that previously reported, but vascular dementia was more predominant. Risk factors for vascular dementia were similar to those for lacunar infarcts. Control of hypertension may be a key to reducing dementia among the Japanese population.
Cranial computed tomographic observations in multi-infarct dementia. A controlled study.
Authors: Gorelick P B , Chatterjee A , Patel D , Flowerdew G , Dollear W , Taber J , Harris Y
Published: June 2011

We compared cranial computed tomography findings among 58 multi-infarct dementia index cases and 74 multi-infarct control subjects without cognitive impairment to identify potential determinants of multi-infarct dementia.

The cranial computed tomography records of acute ischemic stroke patients with a history of multiple cerebral infarcts were compared to determine the number, location, and size of cerebral infarcts; the pattern of infarction; brain volume loss; and the degree of white matter lucency, sulcal enlargement, and ventricular enlargement. Multi-infarct patients were divided into two groups: 1) index cases were defined as those with multi-infarct dementia as defined by the Diagnostic and Statistical Manual of Mental Disorders, edition 3 (DSM-III) criteria; and 2) control subjects were defined as those multi-infarct patients without dementia or multi-infarct dementia according to DSM-III criteria.

Overall, multi-infarct index cases had more cerebral infarcts, more cortical and subcortical left hemisphere infarcts, higher mean ventricular volume to brain volume ratio, more extensive enlargement of the body of the lateral ventricles and cortical sulci, and a higher prevalence of white matter lucencies. Among multi-infarct cases and control subjects the most frequent site of infarction was the subcortical region, and the most frequent pattern of infarction was lacunar. Stepwise logistic regression analysis examined cranial computed tomography as well as other factors and showed that level of education, stroke severity, left cortical infarction, and diffuse enlargement of the left lateral ventricle were the best overall predictors of multi-infarct dementia.

Level of education, stroke severity, and left hemisphere infarction may be predictors of multi-infarct dementia.
Prevalence of extracranial carotid artery disease detectable by echo-Doppler in an elderly population.
Authors: Pujia A , Rubba P , Spencer M P
Published: June 2011

Little information is available on extracranial carotid artery disease in free-living elderly individuals. We sought to evaluate the prevalence of carotid lesions in the elderly.

Using echo-Doppler, we assessed the prevalence of possible atherosclerotic lesions in the internal carotid arteries (n = 478) and the external and common carotid arteries (n = 956) of 239 subjects 65-94 years of age living in retirement homes in Seattle, Wash.

We found that 152 (31.8%) internal carotid arteries were affected by nonstenosing plaque and 37 arteries (7.7%) had stenosis or occlusion. In addition, 193 (20.2%) external or common carotid arteries showed nonstenosing plaques. There were 128 subjects (53.6%) with internal carotid disease, 106 (44.3%) with evidence of external or common carotid disease, and 75 (31.4%) affected by disease in all three sites. There were 80 subjects (33.5%) with no ultrasound evidence of carotid disease. We found that the presence and severity of carotid disease increased between the decades 65-74 and 75-84. We also demonstrated a positive association between systolic blood pressure and ultrasound evidence of carotid disease that was independent of age.

The prevalence of extracranial artery disease in an apparently healthy population was high, although stenoses in most instances were not severe. We conclude that noninvasive ultrasound methods identify a relatively small fraction of individuals (5% of the total) at high risk for stroke or transient ischemic attack. Echo-Doppler might be used to monitor further disease progression and to evaluate the efficacy of different therapeutic or preventive interventions.
European stroke prevention study: effectiveness of antiplatelet therapy in diabetic patients in secondary prevention of stroke.
Authors: Sivenius J , Laakso M , Riekkinen P , Smets P , Lowenthal A
Published: June 2011

The European Stroke Prevention Study was a multicenter trial comparing the effect of a combination of 75 mg dipyridamole and 330 mg acetylsalicylic acid three times a day with the effect of a placebo in the prevention of stroke or death in 1,861 patients after one or more episodes of recent transient ischemic attack or cerebral infarction.

The present study represents a secondary analysis of the efficacy of study medication in diabetic (n = 216) and nondiabetic (n = 1,645) patients.

The risk of end point events was greater in diabetic than in nondiabetic subjects. Total end point reduction in individuals receiving the combination of dipyridamole and acetylsalicylic acid was 39% in nondiabetic subjects and 23% in diabetic subjects in the explanatory analysis, and the reduction in the risk of stroke was 48% and 32%, respectively. However, a statistically significant reduction of risk was obtained only in nondiabetic subjects.

The combination of dipyridamole and acetylsalicylic acid appeared to be more effective in nondiabetic subjects than in diabetic subjects in the prevention of death and stroke although the low number of diabetic patients may at least in part explain this result.
Hemodynamic and metabolic changes in crossed cerebellar hypoperfusion.
Authors: Yamauchi H , Fukuyama H , Kimura J
Published: June 2011

The pathophysiology of crossed cerebellar diaschisis remains to be elucidated. The mechanism responsible appears to be deafferentation through the corticopontocerebellar tract, which terminates in the cerebellar gray matter. However, few studies have demonstrated the hemodynamic and metabolic changes in the cerebellar gray matter and pons in crossed cerebellar diaschisis.

Using positron emission tomography in 24 patients with unilateral supratentorial stroke, we evaluated regional blood flow, metabolic rate of oxygen, oxygen extraction fraction, and blood volume in the cerebellar cortex and pons. Sixteen patients with significant cerebellar blood flow asymmetry, defined as a percentage difference in blood flow beyond the upper 95% confidence limit defined in eight normal subjects, were selected as the group with crossed cerebellar hypoperfusion.

In patients with crossed cerebellar hypoperfusion, the metabolic rate of oxygen was significantly decreased in the cerebellar cortex contralateral to the supratentorial stroke, compared with that in the ipsilateral cerebellar cortex; this decrease was less than the decrease in cerebellar blood flow. The degrees of cerebellar asymmetry in these two parameters were negatively correlated with the metabolic rate of oxygen in the pons. The oxygen extraction fraction was slightly, but significantly, increased. In contrast to the ischemic state, however, the cerebellar blood volume was decreased, with no difference in the ratio of cerebellar blood flow to blood volume.

These findings support interruption of the corticopontocerebellar tract as the mechanism of crossed cerebellar hypoperfusion. Our results also suggest a mild elevation in the oxygen extraction fraction in this state, with a mechanism distinct from ischemia.
Stroke after pituitary irradiation.
Authors: Bowen J , Paulsen C A
Published: June 2011

Cranial irradiation may lead to accelerated atherosclerosis over several years. Stroke has been described after cranial irradiation administered for a number of conditions. However, pituitary irradiation has only rarely been associated with stroke.

Two patients, 39 and 46 years of age, suffered strokes 13 and 20 years, respectively, after irradiation for pituitary tumors. Strokes were in the territories of small perforating arteries, but large vessels such as the carotid siphon and anterior cerebral arteries were also abnormal. Other risk factors for stroke were absent.

It is suggested that pituitary irradiation increases the risk of subsequent stroke due to the known effects of ionizing radiation on vascular walls.
Role of ticlopidine for prevention of stroke.
Authors: Albers G W
Published: June 2011

Ticlopidine, an antiplatelet agent with a unique mechanism of action, is now available for clinical use in the United States and Canada.

Recently two large randomized trials demonstrated that ticlopidine can reduce the risk of subsequent stroke in patients presenting with a transient ischemic attack or stroke. One study found that ticlopidine was more effective than aspirin for stroke prevention; however, it was less well tolerated than aspirin and was associated with severe but reversible neutropenia in almost 1% of patients.

Ticlopidine is effective for both primary and secondary stroke prevention. It has a favorable risk/benefit ratio and is a particularly attractive option for patients who are unable to take aspirin.
Ultrasonic measurement of the elastic modulus of the common carotid artery. The Atherosclerosis Risk in Communities (ARIC) Study.
Authors: Riley W A , Barnes R W , Evans G W , Burke G L
Published: June 2011

The Atherosclerosis Risk in Communities Study is a prospective investigation of the etiology and natural history of atherosclerosis and the etiology of clinical disease in four US communities.

Noninvasive ultrasonic methods were used to determine mean wall thickness (WT), radius (R), and circumferential arterial strain (CAS) in the left common carotid artery of 3,321 white male and female study participants between the ages of 45 and 64 years. The mean and standard deviation of Young's elastic modulus (Y) in 5-year age groups were determined for each sex by combining the ultrasonic data with concurrent noninvasive measurements of pulse pressure (PP) in the right brachial artery using the equation Y = (R/WT) x (PP/CAS).

Significant (p = 0.0001) age group differences in Y were observed in both sexes, with the mean value increasing from 701 kPa in women and 771 kPa in men in the 45-49-year-old age group to 965 and 983 kPa, respectively, in the 60-64-year-old age group. Significant (p = 0.0001) age group differences were also observed for WT, the WT/R ratio, PP, CAS, and the PP/CAS ratio in both sexes. A sex difference in Y was detected (male greater than female, p = 0.0006) only in the 45-49-year-old age group. Significant (p less than 0.0001) sex differences were found, with men having a greater lumen diameter calculated as 2 x (R - WT), a greater WT, and a greater 2R in all age groups. The WT/R ratio did not differ in both sexes in all age groups.

Knowledge of the arterial wall elastic modulus and the parameters required for its determination can provide important insight into structural changes occurring within the arterial wall with age and sex, and possibly with the onset of very early arterial disease.
Doppler CO2 test as an indicator of cerebral vasoreactivity and prognosis in severe intracranial hemorrhages.
Authors: Klingelhöfer J , Sander D
Published: June 2011

Transcranial Doppler ultrasonography is a noninvasive, reproducible technique that allows the assessment of CO2-induced cerebral vasomotor reactivity. We investigated the effect of CO2 changes on cerebral blood flow velocity in patients with severe intracranial hemorrhage and evaluated the relation between CO2 reactivity, intracranial pressure, and outcome.

Transcranial Doppler parameters, intracranial pressure, arterial blood pressure, and PaCO2 were measured simultaneously in 40 patients. To determine CO2 reactivity, the initial PaCO2 of each patient was lowered by at least 6 mm Hg by controlled hyperventilation. Relative CO2 reactivity was defined as the percent change in mean flow velocity per mm Hg PaCO2 (averaged during 20 heart cycles before and after approximately 15 minutes of increased hyperventilation).

A significantly reduced relative CO2 reactivity was observed in the patient group compared with a healthy, age-matched control group. Relative CO2 reactivity was maintained significantly better in patients with moderate intracranial pressure than in patients with markedly increased intracranial pressure. An indirect correlation was found between intracranial pressure and relative CO2 reactivity (r = -0.89; p less than 0.001). Clinical outcome was significantly related to the initial relative CO2 reactivity. Whereas the patients with good recovery had shown a largely preserved reactivity (mean +/- SD, 3.4 +/- 0.7%) that did not differ significantly from the control group, there was a continuous decrease up to the patients who died (0.8 +/- 0.3%).

Transcranial Doppler CO2 testing in patients with severe cerebral disease and elevated intracranial pressure provides useful information regarding hemodynamic state, prognosis, and determination of beneficial effects of specific therapy.