bluuebunny/crossref_metadata_2025 huggingface dataset:
A methodological appraisal of research on prognosis after transient ischemic attacks.
Authors: Kernan W N , Feinstein A R , Brass L M
Published: June 2011

We analyzed existing research on the prognosis of patients who have had a transient ischemic attack to identify studies that adhere to basic methodological principles and to identify underinvestigated questions. Studies were eligible for analysis if they were published in peer-reviewed journals after 1950, written in English, and included at least 50 patients with transient ischemia. Studies that included patients with stroke were included only if they reported outcome rates separately for the subgroup of patients with transient ischemia. All eligible studies were extracted by one investigator who recorded adherence to six key methodological principles. Among 60 eligible studies, 54 were observational cohort studies and six were randomized trials. Adherence to the six methodological principles was as follows: eight studies included an adequate description of diagnostic criteria and of procedures used to assure adherence to the criteria, 54 used appropriate end points, two assembled inception cohorts, 10 included an adequate description of end point surveillance, 22 adequately reported and analyzed censored patients, and 10 included a multivariate analysis for predictive variables. No study adhered to all six principles, but two adhered to the three most important ones (appropriate end points, inception cohort, and adequate reporting and analysis of censored patients). Aspects of prognosis after transient ischemia that have not been completely investigated include the severity of subsequent strokes and methods for estimating the outcome risk for individual patients. We conclude that only a few published investigations on prognosis after transient ischemia are methodologically complete. This finding helps explain why it is difficult to interpret many studies. Further research is needed and should target underinvestigated topics.
Carotid stenosis in lacunar stroke.
Authors: Tegeler C H , Shi F , Morgan T
Published: June 2011

The prevalence of extracranial carotid stenosis in patients with a clinical syndrome of lacunar stroke has not been extensively studied using noninvasive methods. We performed carotid duplex sonography on 168 patients referred to the neurosonology laboratory with a diagnosis of ischemic stroke. Strokes were independently classified as lacunar or nonlacunar hemispheric infarction without knowledge of the ultrasound results. We excluded patients with infarcts that were clearly vertebrobasilar, presumed to be cardioembolic, or had occurred greater than 1 year earlier, and patients for whom classification of the nature and location of the event was not possible. Fifty-five patients had lacunar and 54 had nonlacunar stroke. No differences in age, sex, distribution, or prevalence of hypertension, diabetes, prior ischemia, or Hispanic surname existed between the two groups. Tobacco use was more frequent in the nonlacunar group (p less than 0.01). The prevalence of important extracranial carotid stenosis (greater than or equal to 50% diameter reduction) in the lacunar stroke group was 13% (seven of 55) in the ipsilateral and 4% (two of 55) in the contralateral carotid artery. Of the 54 patients with nonlacunar hemispheric stroke, 41% (22) had ipsilateral (p less than 0.01) and 26% (14) had contralateral (p less than 0.01) carotid stenosis. This study suggests that important carotid stenosis is infrequent among patients presenting with a clinical syndrome of lacunar stroke. These data impact on decisions regarding cerebrovascular work-up in such patients.
Assessment of cerebral autoregulation dynamics from simultaneous arterial and venous transcranial Doppler recordings in humans.
Authors: Aaslid R , Newell D W , Stooss R , Sorteberg W , Lindegaard K F
Published: June 2011

We investigated the validity of transcranial Doppler recordings for the analysis of dynamic responses of cerebral autoregulation. We found no significant differences in percentage changes among maximal (centerline) blood flow velocity, cross-sectional mean blood flow velocity, and signal power-estimated blood flow during 24-mm Hg stepwise changes in arterial blood pressure. We investigated blood flow propagation delays in the cerebral circulation with simultaneous Doppler recordings from the middle cerebral artery and the straight sinus. The time for a stepwise decrease in blood flow to propagate through the cerebral circulation was only 200 msec. Brief (1.37-second) carotid artery compression tests also demonstrated that the volume compliance effects of the cerebral vascular bed were small, only about 2.2% of normal blood flow in 1 second. Furthermore, transients associated with inertial and volume compliance died out after 108 msec. We also investigated the hypothesis that autoregulatory responses are influenced by hyperventilation using the same brief carotid artery compressions. One second after release, the flow index increased by 17% during normocapnia and 36% during hypocapnia. After 5 seconds, the flow index demonstrated a clear oscillatory response during hypocapnia that was not seen during normocapnia. These results suggest that the intact human cerebral circulation in the absence of pharmacological influences does not function as predicted from pial vessel observations in animals.
Cerebrovascular disease in Saudi Arabia.
Authors: Yaqub B A , Shamena A R , Kolawole T M , Patel P J
Published: June 2011

We studied the pattern and outcome of strokes in 200 Saudi patients. Cerebral infarction constituted 87% of strokes, subarachnoid hemorrhage 4.5%, cerebral hemorrhage 6.5%, and venous infarction 2%. The vessel most commonly involved was part or all of the middle cerebral artery, constituting 52% (90) of the 174 arterial infarcts. Lacunar infarcts were seen in 21% (37) of the patients with arterial infarcts. Among all 200 patients, 8% died and 8% had secondary generalized seizures. Hypertension occurred in 41% of the 174 patients with arterial infarcts and 62% of the 13 with cerebral hemorrhages. The highest incidence of hypertension as a risk factor was among those with lacunar infarcts (81%), ganglionic cerebral hemorrhages (80%), and infarcts of deep branches of the middle cerebral artery (57%). Embolic infarcts due to rheumatic heart disease constituted 11% of all arterial infarcts. We conclude that our pattern of strokes is similar to that of the west rather than that of the Japanese, but with less frequent arteriovenous malformations and aneurysms.
Mechanisms of impaired endothelium-dependent cerebral vasodilatation in response to bradykinin in hypertensive rats.
Authors: Yang S T , Mayhan W G , Faraci F M , Heistad D D
Published: June 2011

Bradykinin produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats than in normotensive Wistar-Kyoto rats. The goals of this study were to determine the mediator of bradykinin-induced dilatation in cerebral arterioles of rats and to determine whether responses to this mediator are altered in hypertensive rats. Diameter of pial arterioles (20-65 microns) was measured using intravital microscopy in 18 normotensive and 17 hypertensive rats. Superfusion of 3 x 10(-7) M bradykinin dilated pial arterioles by 53 +/- 4% (mean +/- SEM) in normotensive rats but only 33 +/- 6% in hypertensive rats (p less than 0.05 versus normotensive rats). Vasodilatation in response to bradykinin was almost completely inhibited by 280 units/ml catalase in both normotensive and hypertensive rats (n = 7 and n = 7, respectively) whereas 150 units/ml superoxide dismutase (n = 6 and n = 5, respectively) and 1 mM deferoxamine (n = 5 and n = 5, respectively) did not attenuate bradykinin-induced vasodilatation. These findings suggest that hydrogen peroxide is the mediator of bradykinin-induced dilatation in cerebral arterioles of rats. We also examined responses of cerebral arterioles to hydrogen peroxide in five normotensive and six hypertensive rats. Dilator responses of cerebral arterioles to 3.2 x 10(-5) M to 1.6 x 10(-4) M hydrogen peroxide did not differ in normotensive and hypertensive rats, which suggests that impaired dilatation of cerebral arterioles in response to bradykinin is not related to altered responsiveness of smooth muscle to an endothelium-derived relaxing factor.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypoglycemia presenting as basilar artery thrombosis.
Authors: Röther J , Schreiner A , Wentz K U , Hennerici M
Published: June 2011

Following our treatment of a patient with hypoglycemia-induced brain stem symptoms, we examined the possible mechanisms for hypoglycemia presenting as basilar artery disease.

We describe a patient who had progressive brain stem symptoms due to a diet-induced hypoglycemia initially diagnosed as basilar artery thrombosis. Symptoms ceased immediately after intravenous glucose.

Before invasive diagnostic and thrombolytic strategies are considered, hypoglycemia as a rare but important cause of acute brain stem dysfunction must be considered in patients suspected to suffer from basilar artery thrombosis.
Postpartum dissecting aneurysm of the basilar artery.
Authors: Van de Kelft E , Kunnen J , Truyen L , Heytens L
Published: June 2011

Dissecting aneurysms arising from the vertebrobasilar complex are rare and difficult to manage. More of their natural history needs to be known before treatment can be optimized.

We report a postpartum dissecting aneurysm of the right vertebrobasilar artery in a 31-year-old woman that was confirmed by angiographic identification of a double lumen. The intracranial segment of the right vertebral artery was thrombosed proximal to the aneurysm. The patient, managed conservatively, recovered well and, when reexamined 2 months later, was found to be neurologically intact. A repeat angiographic study at that time demonstrated that the aneurysm had resolved.

Proximal occlusion may have protected the aneurysm from rupture and further dissection, thereby making surgery unnecessary.
Seasonal variation of cerebral hemorrhage in 236 consecutive cases in Brussels.
Authors: Capon A , Demeurisse G , Zheng L
Published: June 2011

Seasonal variation in the incidence of cerebral hemorrhage has been previously demonstrated. In this study, we sought to identify the climatological data best correlated with this seasonal variation.

In a retrospectively studied sequential series of 236 patients with nontraumatic cerebral hemorrhage observed in Brussels over a period of 8 years, we cumulatively grouped the dates of stroke occurrence into a single calendar year.

We found marked seasonal variation in incidence, with the highest value (23%) observed in November-December and the lowest (10%) in July-August. Seasonal variations in incidence of cerebral hemorrhage were shown to be correlated not only with the inverse of ambient temperature, but also with the inverse of hours of sunshine and with ambient humidity. We found no difference between hypertensive and normotensive patients.

Our study fails to bear out the hypothesis that the higher incidence of cerebral hemorrhage in late autumn and winter is due to the influence of low ambient temperature on blood pressure.
Combined treatment with MK-801 and nicardipine reduces global ischemic damage in the gerbil.
Authors: Hewitt K , Corbett D
Published: June 2011

Excessive activation of the N-methyl-D-aspartate receptor by glutamate produces an influx of Ca2+, which in turn is thought to lead to ischemic cell death. In this study we evaluated the combined treatment of the N-methyl-D-aspartate antagonist dizocilpine (MK-801) and the dihydropyridine Ca2+ channel blocker nicardipine for the reduction of hippocampal CA1 neuronal loss.

Global ischemia was induced by bilateral carotid artery occlusion in the gerbil. Body temperature was maintained between 36.5 degrees C and 37.5 degrees C during surgery. MK-801 (5.0 mg/kg) was injected 15 minutes after occlusion whereas nicardipine was given by injection and via a micro-osmotic pump (1.0 mg/kg/day) for 3 days.

Postischemic treatment with MK-801 reduced CA1 cell loss by 27.0%, whereas nicardipine reduced CA1 cell loss by 13.3%. Combined postischemic treatment with these drugs yielded an additive, protective effect (44.5% reduction of CA1 loss) that did not appear to result from postischemic hypothermia as assessed by skull and rectal temperature recordings.

Our results demonstrate that MK-801 plus nicardipine significantly attenuates CA1 cell death after forebrain ischemia in the gerbil. Excitatory amino acid antagonists in combination with Ca2+ channel antagonists may be an effective therapy in patients exposed to global ischemic insult.
Transcranial Doppler assessment of cerebral flow velocity during cognitive tasks.
Authors: Kelley R E , Chang J Y , Scheinman N J , Levin B E , Duncan R C , Lee S C
Published: June 2011

The purpose of this study was to assess the ability of transcranial Doppler ultrasonography to detect selective circulatory changes during cognitive activity.

We measured cerebral artery flow velocity in 21 normal volunteers by transcranial Doppler ultrasonography during rest followed by cerebral activation. Mean and peak systolic flow velocities of the anterior, middle, and posterior cerebral arteries were measured during the performance of a commercial video game. We also measured flow velocity of the anterior cerebral arteries in 18 subjects during a mental arithmetic task. Serial measurements of the right and left sides were made with a headband with two probes.

We observed a global increase in the flow velocity above baseline measurements during task performance. During the video game, both middle cerebral arteries (t = 2.6, p = 0.02 for the left; t = 3.3, p = 0.004 for the right) and the left posterior cerebral artery (t = 2.2, p = 0.004) had selective increase in mean flow velocity compared with the ipsilateral anterior cerebral artery. This selective activation was most prominent in the right middle cerebral artery, which had a greater degree of activation than the right posterior cerebral artery (t = 2.8, p = 0.013). We did not observe a statistically significant difference between the right and left middle cerebral arteries, but there was a trend toward a greater activation on the right for both the mean velocity (t = 1.7, p = 0.098) and the peak velocity (t = 1.9, p = 0.079).

Our preliminary investigation suggests that this noninvasive technique has the potential to correlate selective cerebral artery flow dynamics with cognitive activity.
Effects of ischemia duration on neurological outcome, CA1 histopathology, and nonmatching to sample learning in monkeys.
Authors: Scheller M S , Grafe M R , Zornow M H , Fleischer J E
Published: June 2011

Male cynomolgus monkeys (n = 10) were subjected to varying durations of global cerebral ischemia to determine the relation between dose (ischemic duration) and response (outcome).

Each monkey was anesthetized with halothane, and global cerebral ischemia was produced by a neck tourniquet and trimethaphan-induced hypotension. The animal was subjected to 3 (n = 3), 9 (n = 3), or 12 (n = 4) minutes of ischemia. Neurological examinations were performed daily for 30 days or until the monkey was neurologically normal. Approximately 1 month after ischemia, the animal was evaluated for evidence of neurobehavioral abnormalities with the nonmatching to sample test. When testing was complete, the monkey was killed with an overdose of pentobarbital and the brain perfused with formalin and removed for histopathologic analysis, with particular attention devoted to the hippocampal CA1 region.

Monkeys subjected to 3 or 9 minutes of ischemia were neurologically normal (except for a very mild injury in one 9-minute animal) immediately after ischemia and had normal CA1 histology. Monkeys subjected to 12 minutes of ischemia were grossly abnormal neurologically after ischemia, but two of the four animals made a complete recovery (neurological deficit score of 0) by 30 days. Monkeys subjected to 12 minutes of ischemia had mild damage in the CA1 region, with all other brain regions appearing normal. None of the animals had demonstrable decrements in neurobehavioral function as measured by the nonmatching to sample test.

We conclude that neurobehavioral testing after global cerebral ischemia in primates is feasible, but the ischemic time necessary to produce CA1 damage that could potentially be quantified antemortem with the nonmatching to sample test is greater than 12 minutes in cynomolgus monkeys and may produce temporary severe gross neurological abnormalities as well.
Mechanism of cerebral blood flow augmentation by hemodilution in rabbits.
Authors: Korosue K , Heros R C
Published: June 2011

Hemodilution is known to increase cerebral blood flow, but it is not known whether the increase in flow is a direct result of a decrease in viscosity or whether it may be due to compensatory vasodilatation in response to the decrease in oxygen carrying capacity that results from hemodilution. This study is designed to investigate this question.

Changes in regional cerebral blood flow were studied in normal and ischemic brains of 15 and 18 rabbits, respectively. In one group of rabbits graded hemodilution was used to reduce arterial oxygen content progressively in stages; in the second group the arterial oxygen content was reduced in similar stages by progressively larger reductions in the concentration of inspired oxygen (hypoxic hypoxia). In the ischemic animals focal ischemia was produced by embolic occlusion of the right middle cerebral artery.

In the normal rabbits, hypoxic hypoxia and hemodilution resulted in similar progressive increases in cerebral blood flow as arterial oxygen content fell. In the ischemic animals, there was a significant fall in cerebral blood flow in the ischemic region in all groups after arterial occlusion. Hemodilution resulted in a progressive increase in cerebral blood flow in both ischemic and nonischemic regions. With hypoxic hypoxia, however, cerebral blood flow in the ischemic region showed no increase or a slight decrease.

Even though hypoxic hypoxia results in a marked increase in cerebral blood flow in normal brain, it does not significantly change cerebral blood flow in ischemic brain. In contrast, hemodilution resulting in a comparable degree of hypoxemia is capable of significantly increasing cerebral blood flow in ischemic brain. Therefore, the mechanism of blood flow augmentation by hemodilution in ischemic brain is probably related to a direct hemorheologic effect rather than to the resulting hypoxemia.
Effect of diabetes mellitus on flow-mediated and endothelium-dependent dilatation of the rat basilar artery.
Authors: Fujii K , Heistad D D , Faraci F M
Published: June 2011

Diabetes mellitus may impair endothelium-dependent responses in cerebral arterioles. The basilar artery dilates in response to increases in blood flow. The goal of this study was to examine effects of diabetes mellitus on "flow-mediated" and endothelium-dependent dilatation of the basilar artery.

Diabetes was induced in rats with 50 mg/kg streptozotocin. Six months later, vessel diameter and velocity of blood flow through the basilar artery were measured using a cranial window in anesthetized rats under baseline conditions and during occlusion of the carotid arteries. Changes in vessel diameter were also measured during topical application of acetylcholine and sodium nitroprusside.

With aortic pressure maintained at baseline levels, blood flow velocity through the basilar artery increased similarly in control and diabetic rats during unilateral common carotid artery occlusion and during bilateral occlusion. In control and diabetic rats, diameter of the basilar artery increased by 10 +/- 2% and 10 +/- 4% during unilateral occlusion and by 27 +/- 5% and 31 +/- 4% during bilateral occlusion, respectively. Thus, diabetes did not impair flow-mediated dilatation of the basilar artery. In contrast, dilatation in response to 10(-5) M topical acetylcholine was less in diabetic rats (13 +/- 2%) than in control rats (45 +/- 8%) (p less than 0.05). Dilator responses to nitroprusside were not impaired by diabetes.

The findings suggest that diabetes produces impairment of endothelium-dependent responses to acetylcholine, but not flow-mediated dilatation, in the basilar artery.
Superoxide production in experimental seizures in cats.
Authors: Bauknight G C , Wei E P , Kontos H A
Published: June 2011

Seizures cause cerebrovascular responses similar to those seen in conditions such as acute hypertension, ischemia/reperfusion, or fluid-percussion brain injury, which are associated with the generation of superoxide. Accordingly, we studied production of superoxide in experimental seizures.

Superoxide production was measured in anesthetized cats equipped with double cranial windows using the superoxide dismutase-inhibitable reduction of nitro blue tetrazolium as a measure of superoxide production. Seizures were induced by intravenous bicuculline. The contribution of hypertension associated with seizures was studied by maintaining arterial blood pressure constant by bleeding.

Significant superoxide dismutase-inhibitable reduction of nitro blue tetrazolium indicative of superoxide production was found during seizures with or without control of arterial blood pressure (1.10 +/- 0.27 and 1.29 +/- 0.16 nmol/l/min, respectively).

The results show that experimental seizures are associated with superoxide generation that is independent of the rise in arterial blood pressure. It is likely that superoxide generation is due to the metabolic changes that occur during seizures.
Endothelium-derived relaxing factor modulates noradrenergic constriction of cerebral arterioles in rabbits.
Authors: Bauknight G C , Faraci F M , Heistad D D
Published: June 2011

Cerebral arterioles are relatively unresponsive to norepinephrine. We tested the hypothesis that release of endothelium-derived relaxing factor is stimulated by norepinephrine and attenuates adrenergic constriction of pial arterioles.

In seven anesthetized New Zealand White rabbits, diameter of pial arterioles was measured through a cranial window. Responses to topical application of norepinephrine and arginine vasopressin were examined before and during application of NG-nitro-L-arginine, which inhibits synthesis of endothelium-derived relaxing factor.

Norepinephrine (10(-6) M) had no effect (0 +/- 3%, mean +/- SE) on arteriolar diameter under basal conditions. Norepinephrine decreased arteriolar diameter by 15 +/- 4% during application of nitro-L-arginine (10(-4) M) (p less than 0.05 versus basal response). L-arginine inhibited the effect of nitro-L-arginine on responses of pial arterioles to norepinephrine. In contrast to norepinephrine, constrictor responses of pial arterioles to vasopressin were not potentiated by nitro-L-arginine.

Norepinephrine, but not arginine vasopressin, releases endothelium-derived relaxing factor, which inhibits constrictor responses of cerebral arterioles in rabbits. This mechanism contributes to the finding that cerebral vessels in rabbits are relatively unresponsive to noradrenergic stimuli.
Abnormalities at different levels of the hypothalamic-pituitary-adrenocortical axis early after stroke.
Authors: Olsson T , Marklund N , Gustafson Y , Näsman B
Published: June 2011

Hypercortisolism is common in stroke patients. The aim of this study was to investigate possible disturbances at different sites within the hypothalamic-pituitary-adrenal axis. We also studied possible associations between hypercortisolism and clinical manifestations of brain dysfunction.

Patients with an acute ischemic stroke (n = 16; mean +/- SD age, 71 +/- 11 years) were compared with healthy elderly subjects (n = 9). We performed a short adrenocorticotropic hormone (ACTH) test with 0.25 mg 1-24 ACTH injected intravenously and an overnight dexamethasone suppression test with 1 mg dexamethasone given orally at 11 PM.

Serum cortisol levels after dexamethasone at 8 AM were significantly higher in stroke patients (p = 0.003). The area under the curve for the cortisol response to ACTH was elevated in seven (47%) of stroke patients, and the centered cumulative cortisol response was elevated in three (20%) patients. The area under the curve response correlated significantly to the presence of an acute confusional state and male sex in stroke patients (rs = 0.63 and rs = 0.62, respectively; p < 0.05), whereas the centered cumulative cortisol response diminished with increasing age (rs = -0.62; p < 0.05). Postdexamethasone cortisol levels were significantly correlated to the presence of an acute confusional state and to extensive limb paresis (rs = 0.66 and rs = 0.62, respectively; p < 0.05).

There are abnormalities in the cortisol axis both at the central level and at the adrenal level early after stroke. Hypercortisolism is closely associated with cognitive disturbances and extensive motor impairment.
Cerebral vasoconstriction in response to hypocapnia is maintained after ischemia/reperfusion injury in newborn pigs.
Authors: Mirro R , Lowery-Smith L , Armstead W M , Shibata M , Zuckerman S L , Leffler C W
Published: June 2011

Hypocapnic cerebral vasoconstriction is used therapeutically to reduce elevated intracranial pressure caused by cerebral edema. Because cerebral ischemia/reperfusion injury causes a selective loss of prostanoid-dependent responses, including vasodilation to hypercapnia, we designed these experiments to examine the effect of ischemia/reperfusion on hypocapnic cerebral vasoconstriction.

Microvascular responses were studied in 10 newborn pigs (closed cranial window) in response to hyperventilation-induced hypocapnia (PaCO2, 22 +/- 2 mm Hg) both before and 45 minutes after 20 minutes of global cerebral ischemia. Responses to hypercapnia (PaCO2, 63 +/- 3 mm Hg), topical isoproterenol (10(-7) M), and norepinephrine (10(-4) M) were also studied before and after ischemia in the same animals for comparison.

Before ischemia/reperfusion, pial arterioles vasoconstricted to hypocapnia (-17 +/- 2%) and norepinephrine (-35 +/- 4%) and vasodilated to CO2 (37 +/- 7%) and isoproterenol (25 +/- 2%). After ischemia/reperfusion, the constriction of pial arterioles to hypocapnia (-19 +/- 2%) was similar to that before ischemia. This is in contrast to the loss of dilation to hypercapnia. Dilation to isoproterenol and constriction to norepinephrine were not affected by ischemia.

Hypocapnic cerebral vasoconstriction is maintained after ischemia/reperfusion. Since prostanoid-dependent responses, such as hypercapnic dilation, are lost following cerebral ischemia, these data suggest that hypocapnic constriction is not dependent on an intact prostanoid system and that cerebral vascular responses to CO2 involve multiple mechanisms, depending on whether CO2 is increasing or decreasing from baseline.
Fructose-1,6-bisphosphate stabilizes brain intracellular calcium during hypoxia in rats.
Authors: Bickler P E , Kelleher J A
Published: June 2011

Exogenously administered fructose-1,6-bisphosphate reduces neuronal injury from hypoxic or ischemic brain insults. To test the hypothesis that fructose-1,6-bisphosphate prevents changes in intracellular calcium ([Ca2+]i) and high-energy phosphate levels, we measured [Ca2+]i, intracellular pH (pHi), and adenosine triphosphate in cultured rat cortical astrocytes and cortical brain slices during hypoxia.

The fluorescent indicators fura-2 and bis-carboxyethyl-carboxyfluorescein were used to simultaneously measure [Ca2+]i and pHi with a fluorometer.

Exposure to hypoxia (95% N2, 5% CO2) or 100 microM sodium cyanide produced transient increases in [Ca2+]i in astrocytes and sustained increases in [Ca2+]i in brain slices. Adenosine triphosphate levels fell in slices exposed to hypoxia or cyanide. Fructose-1,6-bisphosphate (3.5 mM) blocked increases in [Ca2+]i and prevented depletion of adenosine triphosphate. Fructose-1,6-bisphosphate also partially prevented adenosine triphosphate depletion in brain slices incubated in glucose-free medium. Iodoacetate (a specific inhibitor of glycolysis) elevated [Ca2+]i and partially prevented these actions of fructose-1,6-bisphosphate. Changes in pHi during hypoxia were not affected by fructose-1,6-bisphosphate.

Fructose-1,6-bisphosphate supports adenosine triphosphate production via stimulation of glycolysis and results in the maintenance of normal [Ca2+]i during hypoxia or hypoglycemia.
Effects in cats of inhibition of nitric oxide synthesis on cerebral vasodilation and endothelium-derived relaxing factor from acetylcholine.
Authors: Wei E P , Kukreja R , Kontos H A
Published: June 2011

We investigated the chemical identity of the endothelium-derived relaxing factor generated by acetylcholine in cerebral microvessels by studying the effects and mechanism of action of inhibitors of nitric oxide synthesis from arginine on the vasodilation and endothelium-derived relaxing factor production induced by topical application of acetylcholine in cerebral arterioles.

We determined cerebral arteriolar dilation and endothelium-derived relaxing factor production by bioassay in anesthetized cats equipped with cranial windows during superfusion of 10(-7) M acetylcholine before and after administration of either NG-monomethyl L-arginine or NG-nitro-L-arginine, two inhibitors of nitric oxide synthesis.

NG-Nitro-L-arginine abolished the vasodilation from acetylcholine and eliminated the production of endothelium-derived relaxing factor in the bioassay experiments. NG-Monomethyl L-arginine had no effect on the response to acetylcholine in the absence of pretreatment. However, after pretreatment with the detergent sodium dodecyl sulfate to increase cell membrane permeability, the inhibitor had effects identical to those of NG-nitro-L-arginine. L-Arginine reversed the effects of the inhibitors of nitric oxide synthesis. Neither inhibitor affected baseline vascular caliber, nor did they generate a vasoconstrictor agent in the bioassay experiments. The two inhibitors of nitric oxide synthesis did not affect the response to nitroprusside or adenosine, showing that the effect on responses to acetylcholine was specific. Also, the blockade of the response to acetylcholine induced by the inhibitors of nitric oxide synthesis was unaffected by treatment with superoxide dismutase and catalase, showing that the effect was not mediated by oxygen radicals.

The endothelium-derived relaxing factor generated by acetylcholine in cerebral arterioles of cats is either nitric oxide or a nitric oxide-containing substance. The effect of these inhibitors on the response to acetylcholine is mediated by inhibition of the synthesis of nitric oxide. There is no involvement of radicals, and no vasoconstrictor agent is generated.
Detection of intracranial emboli in patients with symptomatic extracranial carotid artery disease.
Authors: Siebler M , Sitzer M , Steinmetz H
Published: June 2011

Cerebral embolism from extracranial sources is an important cause of ischemic stroke. The purpose of this limited study using long-term transcranial Doppler ultrasonographic monitoring was to estimate the frequency of clinically silent intracranial embolisms in patients with symptomatic extracranial carotid artery disease.

By means of a 2-MHz pulsed-wave transcranial Doppler instrumentation, three consecutive patients with extracranial internal carotid artery stenosis (n = 2) or occlusion (n = 1) and recurrent ipsilateral ischemic events were monitored (19 hours total recording time). In addition, 10 control subjects without cerebrovascular disease were studied (25 hours total recording time). Formed-element emboli were defined as distinct signals within the fast Fourier-transform Doppler spectrum that were < 70 msec in duration and > 9dB greater in intensity than the background signal. Clinically silent formed-element embolism of ophthalmic or cerebral arteries was demonstrated in all three patients. Embolic events occurred only in the territory of the symptomatic internal carotid artery. The average rate of cerebral embolization at transcranial Doppler ultrasonography was 4.1/hr, with a mean signal duration of 47 msec. No emboli were found in control subjects.

The observed high frequency of silent embolism of the intracranial arteries detected by transcranial Doppler monitoring in patients with recurrently symptomatic extracranial carotid artery disease should encourage studies of the prognostic and therapeutic implications of this method.
Irish brogue after stroke.
Authors: Seliger G M , Abrams G M , Horton A
Published: June 2011

We describe a patient who presented a unique variation of the previously described acquired foreign accent syndrome.

A 65-year-old women developed an Irish brogue immediately after a deep left hemisphere stroke. The newly accented speech possibly represented a previously learned speech pattern.

Suppressed prosodic speech patterns may reemerge in the setting of brain injury.
The role of transesophageal echocardiography in the acute onset of paraplegia.
Authors: Walsh D V , Uppal J A , Karalis D G , Chandrasekaran K
Published: June 2011

Acute paraplegia must be investigated promptly to exclude reversible causes. In this report we illustrate the usefulness of transesophageal echocardiography in identifying the vascular etiologies of acute paraplegia.

Two patients presented with acute paraplegia, one spontaneously and the other after removal of an intra-aortic balloon pump catheter. Through the use of transesophageal echocardiography, we excluded aortic dissection and identified protruding atherosclerotic plaques in the descending thoracic aorta of each patient. Embolization of atheromatous material from the thoracic aorta was considered the most likely etiology of paraplegia in both cases.

Embolization from atherosclerotic plaques in the thoracic aorta may be an underestimated cause of acute paraplegia. Transesophageal echocardiography provides a safe, rapid, and reliable tool for investigating a vascular etiology of acute paraplegia.
Thrombotic occlusion of the middle cerebral artery.
Authors: Ueda S , Fujitsu K , Inomori S , Kuwabara T
Published: June 2011

Epidemiological study of middle cerebral artery occlusion is important because the indication for extracranial-intracranial arterial bypass remains in dispute. To help clarify this issue, we investigated the prognosis of thrombotic middle cerebral artery occlusion in Japanese patients.

We studied 40 patients with thrombotic middle cerebral artery occlusion who were selected on the basis of clinical features, computed tomographic findings, and angiographic findings. Patients with causes of embolism (i.e., cardiomyopathy, valvular heart disease, cardiac arrhythmia, and carotid ulceration) were excluded. The 40 patients were classified into three groups according to the site of middle cerebral artery occlusion: there were 13 patients with occlusion of the proximal portion of the M1 segment, 13 with distal M1 segment occlusion, and 14 with occlusion of the M2 segment.

Good collateral circulation was associated with improved outcomes both clinically and by computed tomography in patients with occlusion of the proximal and distal portions of the M1 segment but not in those with M2 occlusion.

It is reasonable to assume that not only collateral circulation but also the site of occlusion plays an important role in the outcome of middle cerebral artery occlusion. Our finding that good collateral circulation improves the outcome for thrombotic occlusion of the proximal and distal M1 segments supports the possible benefits of such surgery.
Hydroxyethyl starch 200/0.5 reduces infarct volume after embolic stroke in rats.
Authors: Perez-Trepichio A D , Furlan A J , Little J R , Jones S C
Published: June 2011

We evaluated isovolumic hemodilution with hydroxyethyl starch 200/0.5 in a rat model of focal cerebral ischemia. This compound avoids the unfavorable viscosity and erythrocyte aggregation abnormalities of low molecular weight dextran during administration over a period of several days.

Sprague-Dawley rats, anesthetized with 0.5-1% halothane and 70% N2O, were subjected to silicon cylinder (treated and control groups) or sham (sham group) embolization of the cerebral circulation. Thirty minutes after embolization, the treated group (n = 5) was infused with 11 ml/kg of 10% hydroxyethyl starch 200/0.5, and the control (n = 5) and sham (n = 4) groups were infused with saline for 1 hour. In the treated group, 7.1 ml/kg of blood was withdrawn. After 24 hours, the animals were reanesthetized, and cerebral blood flow was determined with [14C]iodoantipyrine. Alternative brain slices were either incubated with 2,3,5-triphenyltetrazolium chloride for infarct volume determination or frozen for ischemic volume and cerebral blood flow determination using autoradiography.

The hematocrit in the treated group was reduced from (mean +/- SEM) 46 +/- 1% to 35 +/- 2% at 1.5 hours (p < 0.01). Cortical blood flow was within the normal range of 115-185 ml/min/100 g, except for the ischemic cortex in the embolized groups, treated and control. The ischemic and infarct volume of the treated group was reduced by 74% (p < 0.05) and 89% (p < 0.05), respectively, from the control group. The treated and sham ischemic and infarct volumes were not statistically different.

These data suggest that hydroxyethyl starch 200/0.5 could be an effective treatment for ischemic stroke when administered early, because it reduces infarct and ischemic volumes from control values to levels indistinguishable from those of the sham group.
Clinical presentation as a guide to early prognosis in vertebrobasilar stroke.
Authors: Nadeau S , Jordan J , Mishra S
Published: June 2011

This study attempts to assess the feasibility and heuristic value of a classification scheme for vertebrobasilar stroke.

Fifty-seven consecutive patients with vertebrobasilar stroke were classified on the basis of clinical features and computed tomographic abnormalities into single-sector (n = 19), multisector (n = 11), and top-of-the-basilar (n = 27) groups; a sector was defined as that portion of the brain stem supplied by a single penetrating (median) or branch (paramedian or lateral) artery.

Thirty-day and 3-year survival rates were 100% and 71%, respectively, in the single-sector group, and 96% and 73%, respectively, in the top-of-the-basilar group. Thirty-day and 3-year stroke recurrence free survival rates were 89% and 76%, respectively, in the single-sector group, and 96% and 88%, respectively, in the top-of-the-basilar group. Seven of the 11 patients in the multisector group died within 2 months of ictus, three having experienced recurrence.

These data, in part supported by prior studies, demonstrate the feasibility and heuristic value of the classification scheme and suggest that single-sector and top-of-the-basilar stroke patients have a relatively benign early prognosis and modest long-term stroke rates.
The International Cooperative Study on the Timing of Aneurysm Surgery. The North American experience.
Authors: Haley E C , Kassell N F , Torner J C
Published: June 2011

The timing of aneurysm surgery after subarachnoid hemorrhage is a major neurosurgical controversy addressed by the International Cooperative Study on the Timing of Aneurysm Surgery (1980-1983). The present report examines the results of this trial in the subgroup of patients admitted to North American centers.

The method of study was a large, multicenter, prospective, epidemiological survey. Neurosurgeons were required to indicate prospectively the interval to planned aneurysm surgery at the time of patient admission. Outcome at 6 months was determined by a blinded evaluator, and overall management results were analyzed by the planned surgical interval.

Seven hundred seventy-two (21.9% of the total study population) patients admitted from days 0 to 3 after subarachnoid hemorrhage were accrued in North American centers. Overall outcome in patients planned for surgery in days 0-3 was equivalent in terms of mortality (after adjustment for prognostic variables) to patients planned for days 11-32, but the early patients had significantly improved rates of good recovery (70.9% versus 61.7%, p less than 0.01). Patients planned for surgery during the days 7-10 interval had nearly twice the mortality of patients in the other intervals.

In contrast to the results from the overall trial, which found no difference between early and delayed surgery, results were best in North American centers when surgery was planned between days 0 and 3 after subarachnoid hemorrhage. These findings argue strongly for early diagnosis and referral for surgical intervention of North American patients suspected of having a ruptured cerebral aneurysm.
Cerebral cysticercosis and stroke.
Authors: Alarcón F , Hidalgo F , Moncayo J , Viñán I , Dueñas G
Published: June 2011

In 1985 we initiated a protocol for examining the relationship between cerebral cysticercosis and stroke.

In 420 stroke patients admitted to our department, our standard protocol of tests included blood tests, cardiac investigations, angiography, and immunologic cerebrospinal fluid measures. We assessed the following possible risk factors: arterial hypertension, diabetes, cardiopathy, high levels of cholesterol and triglycerides, smoking, alcohol abuse, and cerebral cysticercosis.

Of the 420 patients with stroke, we found cerebral cysticercosis in 31, five of whom were greater than 65 years of age and 26 of whom were less than or equal to 65 years. We determined that cerebral cysticercosis was the only possible risk factor for stroke in one of the five older patients and 15 of the 26 younger and middle-aged patients. Cortical infarctions were found in five of the 31 patients, with cerebral cysticercosis and lacunar infarctions in nine of these patients. One patient had intracystic hemorrhage. In 16 cases, neurological deficit was related to single or multiple cysts, colloids, granulomas, diffuse lesions, or pericystic edema. All patients with cerebral cysticercosis quickly recovered from their neurological deficit, except one who had a hemorrhagic cyst and died and another who remained disabled.

We established that, in patients with neurocysticercosis, occlusion of the small cortical or penetrating vessels at the base of the brain caused by arteriopathy was the most common mechanism of the stroke. Moreover, there is a probable association between cerebral cysticercosis and the susceptibility to stroke, particularly among young and middle-aged patients.
Siagoside selectively attenuates morphological and functional striatal impairments induced by transient forebrain ischemia in rats.
Authors: Merlo Pich E , Grimaldi R , Zoli M , Biagini G , Solfrini V , Toffano G , Fuxe K , Agnati L F
Published: June 2011

Transient forebrain ischemia induced in rats by the four-vessel occlusion method is known to produce severe neural damage in the hippocampus and striatum and a behavioral syndrome the major symptom of which is a working memory deficit. Recent evidence suggests that monosialogangliosides can ameliorate postischemic symptoms. Our purpose was to study the effect of siagoside, the inner ester of GM1 ganglioside, on some behavioral and morphological impairments induced by four-vessel occlusion in rats.

Rats were injected daily with 5 mg/kg i.p. siagoside starting 4 hours after the cerebral ischemia. After 14 days the rats were tested for working memory in a water T maze or scored for apomorphine-induced stereotypy. The rats were killed 21 days after the cerebral ischemia. Histological and computer-assisted morphometric analyses were performed on cresyl violet-stained brain sections, which were graded according to a neuropathologic score, and on sections stained with a monoclonal antiserum against dopamine and cyclic adenosine-3',5'-monophosphate-regulated phosphoprotein, a marker for striatal dopaminoceptive neurons.

Siagoside treatment reduced the stereotypy score induced by low doses of apomorphine and the extent of striatal lesions but did not affect the working memory deficit or the extent of hippocampal lesions.

Daily siagoside treatment after acute cerebral ischemia attenuates some morphological and functional deficits related to striatal damage. These effects can be interpreted as a selective protective action on striatal neural populations or as a modulatory action on neural systems involved in striatal control. These data are consistent with preliminary clinical reports showing that monosialogangliosides enhance motor recovery after acute ischemic stroke.
Monoclonal leukocyte antibody does not decrease the injury of transient focal cerebral ischemia in cats.
Authors: Takeshima R , Kirsch J R , Koehler R C , Gomoll A W , Traystman R J
Published: June 2011

We tested the hypothesis that inhibition of leukocyte function by administration of monoclonal antibody 60.3 (MoAb 60.3) improves electrophysiological recovery and decreases injury volume following transient focal cerebral ischemia in cats.

Halothane-anesthetized cats underwent 90 minutes of left middle cerebral artery and bilateral common carotid artery occlusion followed by 180 minutes of reperfusion. Cats were assigned to receive either 2 mg/kg MoAb 60.3 (n = 8) directed at the CDw18 leukocyte antigen complex or an equal volume of diluent (sterile saline; n = 10) at 45 minutes of ischemia in a blinded fashion.

Blood flow to the left temporoparietal cortex decreased to less than 5 ml/min/100 g with ischemia, but was minimally affected on the right side. Postischemic hyperemia occurred in the left caudate nucleus, whereas blood flow in other brain regions returned to control. No region demonstrated delayed hypoperfusion, and there were no differences between groups. Somatosensory evoked potential recorded over the left cortex was ablated during ischemia and recovered to less than 10% of baseline amplitude at 180 minutes of reperfusion in both groups. Left hemispheric injury volume, as assessed by 2,3,5-triphenyltetrazolium chloride staining, was not affected by drug treatment (mean +/- SE values: MoAb 60.3, 37 +/- 5%; placebo, 38 +/- 7% of hemisphere).

Inhibition of leukocyte function with MoAb 60.3 does not afford protection from severe focal ischemia and reperfusion in cats.
Neurological and behavioral outcomes of focal cerebral ischemia in rats.
Authors: Wahl F , Allix M , Plotkine M , Boulu R G
Published: June 2011

The aim of this study was to investigate the neurobehavioral consequences of focal ischemia in rats.

We induced permanent occlusion of the left middle cerebral artery in 14 Sprague-Dawley rats, and used 13 sham-operated rats as controls. During surgery, brain temperature and body temperature were kept at normothermia. Neurobehavioral studies (neurological examination, passive avoidance task, Y maze test, and modified open-field test) were carried out 4 days after ischemia before killing the rats to evaluate histological damage.

Ischemia induced large infarcts in the cortex (138.6 +/- 8.5 mm3) and caudate-putamen (48.8 +/- 2.6 mm3) and, compared with sham-operated rats, produced a dramatic neurological deficit (p less than 0.001) characterized by sensorimotor dysfunctions and hemiplegia. Memory retention was significantly (p less than 0.05) impaired in the passive avoidance task, but neither vigilance and exploratory behavior measured in the modified open-field test nor working memory evaluated in the Y maze test were disturbed. Infarct size was not correlated with the neurological or behavioral deficits.

This lack of correlation indicates the necessity of carrying out parallel histological, neurological, and behavioral studies in any assays of new drugs using this model of focal ischemia.
Bilateral middle cerebral artery occlusions in neurocysticercosis.
Authors: terPenning B , Litchman C D , Heier L
Published: June 2011

Bilateral hemispheric strokes in a young adult are very rare. We describe a case of neurocysticercosis in a young male with bilateral middle cerebral artery occlusions.

Axial tomographic imaging revealed lesions compatible with cysticerci adjacent to each middle cerebral artery initial segment, and occlusion of both arteries at that level was demonstrated by angiography. Extensive medical workup disclosed no other risk factors for stroke.

Neurocysticercosis should be considered in the differential diagnosis of stroke in a young patient.