bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebral vasoreactivity in unilateral carotid artery disease. A comparison of blood flow velocity and regional cerebral blood flow measurements.
Authors: Dahl A , Russell D , Nyberg-Hansen R , Rootwelt K , Bakke S J 
Published: June 2011

Hemodynamic information obtained by assessing cerebral vasoreactivity is of clinical interest and may have prognostic significance in patients with occlusive carotid disease. The aim of this study was to compare the results of transcranial Doppler and regional cerebral blood flow studies when used to assess cerebral vasoreactivity.
Blood flow velocities in both middle cerebral arteries and regional cerebral blood flow in their respective perfusion territories were compared in 52 patients with severe unilateral carotid stenosis or occlusion. The studies were first performed under basal conditions and repeated after the intravenous administration of 1 g acetazolamide.
Asymmetry (normal compared with pathological side) in middle cerebral artery blood velocity increase was significantly greater than the asymmetry in cerebral blood flow increase in the perfusion territories of the arteries. A significant correlation (r = .63, P < .0001) was found between asymmetry in percent velocity increase and asymmetry in absolute cerebral blood flow increase. The two methods agreed in their assessment of either a normal or a reduced vasoreactivity in 38 subjects and disagreed in 14. In six of the latter patients, who had no evidence of cerebral infarction, the asymmetry in velocity increase was abnormal, whereas asymmetry in flow increase was assessed as normal.
We found a good correlation between the asymmetry in regional cerebral blood flow increase in the middle cerebral artery perfusion territories and asymmetry in the velocity increase in the middle cerebral arteries after administration of acetazolamide. These results suggest that transcranial Doppler examination combined with the acetazolamide test may be used in clinical situations to assess cerebral vasoreactivity.
A comparison of intra-arterial and intravenous tissue-type plasminogen activator on autologous arterial emboli in the cerebral circulation of rabbits.
Authors: Hamilton M G , Lee J S , Cummings P J , Zabramski J M 
Published: June 2011

The efficacy of thrombolytic therapy for treatment of embolic stroke has been a subject of both experimental and clinical examination. The aim of this study was to compare the efficacy, in regard to reduction of volume of ischemic brain, of two different modes of administration (ie, intra-arterial and intravenous) of tissue-type plasminogen activator (TPA) given 30 minutes after experimental embolic stroke in rabbits.
A randomized, blinded, controlled experimental trial was undertaken. Embolic stroke was simulated in rabbits by injecting fragments of autologous arterial thrombus into one internal carotid artery. Thirty minutes after embolization, the rabbits were blindly treated with 2 mg/kg intra-arterial TPA, 2 mg/kg intravenous TPA, or saline (all n = 10). Six hours after embolization the rabbits were killed. The brains were perfused with triphenyltetrazolium chloride and cut into 0.5-cm-thick coronal sections, and the areas of ischemia were measured.
Administration of TPA resulted in a significant reduction in the volume of ischemic cerebral injury (P < .0001): control animals sustained ischemic injury to 20.1 +/- 4.6% (mean +/- SD) of total brain compared with 4.6 +/- 4.1% for animals treated with intra-arterial TPA and 3.4 +/- 2.6% for those treated with intravenous TPA. The difference between intra-arterial and intravenous TPA treatment was not significant (P = .786).
In this rabbit model of embolic stroke, administration of TPA within 30 minutes resulted in a dramatic reduction in the amount of ischemic injury, with equal efficacy for the two modes of administration. These results favor the treatment of acute embolic stroke with intravenous TPA, given the rapidity with which intravenous therapy can be established in the clinical setting.
An experimental model of symptomatic vasospasm induced by oxyhemoglobin in rabbits.
Authors: Otsuji T , Endo S , Hirashima Y , Nishijima M , Takaku A 
Published: June 2011

There are many experimental models for studies of cerebral vasospasm. However, no ideal model has been established thus far to comparatively reproduce the ischemic state of the brain that may occur in patients after subarachnoid hemorrhage.
In the present study, we attempted to induce severe vasospasm in rabbits by using an oxyhemoglobin-rich blood product prepared from hemolyzed arterial blood and evaluate neurological symptoms, cerebral angiogram, cerebral blood flow, and histology.
Clinically significant neurological symptoms were observed in about half of the rabbits. There was no significant correlation between angiographic results of the vasospastic state of the main artery and the severity of neurological symptoms observed. However, the cerebral blood flow was significantly lower than in the control group and significantly correlated with the severity of neurological symptoms. On histological examination, lesions were found in about half of the rabbits. Development of obvious infarction was found more frequently than in other reported models.
These results suggest that this model is appropriate as an experimental model of vasospasm occurring after subarachnoid hemorrhage and is especially useful in that it induces vasospasm intense enough to cause obvious infarction.
Neuroprotection with a calpain inhibitor in a model of focal cerebral ischemia.
Authors: Hong S C , Goto Y , Lanzino G , Soleau S , Kassell N F , Lee K S 
Published: June 2011

Excessive elevation of intracellular calcium and uncontrolled activation of calcium-sensitive events are believed to play a central role in ischemic neuronal damage. Calcium-activated proteolysis by calpain is a candidate to participate in this form of pathology because it is activated under ischemic conditions and its activation results in the degradation of crucial cytoskeletal and regulatory proteins. The present studies examined the effects of a cell-penetrating inhibitor of calpain on the pathological outcome after transient focal ischemia in the brain.
Twenty-five male Sprague-Dawley rats were divided into four groups: a saline-treated group, a vehicle-treated group, and two calpain inhibitor-treated groups (Cbz-Val-Phe-H; 30-mg/kg and 60-mg/kg cumulative doses). Ischemia was induced by occluding the left middle cerebral artery and both common carotid arteries for 3 hours followed by reperfusion. Animals were killed 72 hours after surgery, and quantitative measurements of infarction volumes were performed using histological techniques. Eight additional rats were killed 30 minutes after ischemia and examined for the extent of proteolysis using immunoblot techniques. A final group of 12 animals was decapitated after injection of vehicle or calpain inhibitor, and the proteolytic response was measured after 60 minutes of total ischemia.
Rats treated with Cbz-Val-Phe-H exhibited significantly smaller volumes of cerebral infarction than saline-treated or vehicle-treated control animals. Intravenous injections of cumulative doses of 30 mg/kg or 60 mg/kg of Cbz-Val-Phe-H were effective in reducing infarction, edema, and calcium-activated proteolysis. The proteolytic response to postdecapitation ischemia was also reduced by the calpain inhibitor.
These results demonstrate the neuroprotective effect of a cell-penetrating calpain inhibitor when administered systemically. The findings suggest that targeting intracellular, calcium-activated mechanisms, such as proteolysis, represents a viable therapeutic strategy for limiting neurological damage after ischemia.
Pilot study of low-molecular-weight heparin in the treatment of acute ischemic stroke.
Authors: Kay R , Wong K S , Woo J 
Published: June 2011

Our purpose was to assess the feasibility and risk of performing a double-blind placebo-controlled study of low-molecular-weight heparin in the treatment of acute ischemic stroke.
Fifty-five patients were treated within 48 hours of stroke onset. Pretreatment computed tomography was performed to rule out cerebral hemorrhage. Fraxiparine (6000 IU per day) was given subcutaneously for 7 days. No adverse reaction was encountered during the treatment period. At 3 months, 26 patients were independent, 21 moderately disabled, 4 severely disabled, and 4 dead.
It would be safe and practical to conduct a clinical trial on the use of Fraxiparine in the treatment of acute ischemic stroke.
Acute bilateral cerebellar infarction in the territory of the medial branches of posterior inferior cerebellar arteries.
Authors: Tada Y , Mizutani T , Nishimura T , Tamura M , Mori N 
Published: June 2011

We describe the first clinicoradiological report of acute bilateral cerebellar infarction confined to the territory of the medial branches of the posterior inferior cerebellar arteries.
A 65-year-old man with atrial fibrillation and hypertension had sudden onset of vertigo, followed by brief loss of consciousness. Three days later a cranial computed tomographic scan showed acute hydrocephalus and low-density areas in the cerebellar vermis on both sides. On transfer the patient showed mild dysarthria, dysequilibrium with retropulsion, symmetrical bilateral horizontal gaze-evoked nystagmus on lateral gaze, and marked gait ataxia without brain stem signs, followed by marked vertigo that was induced by motion. Cranial magnetic resonance imaging revealed abnormalities consistent with fairly symmetrical bilateral cerebellar hemorrhagic infarction that was confined to the territory of the medial branches of the posterior inferior cerebellar arteries, in addition to minimal high-intensity areas in the pons on T2-weighted images. The patient improved with conservative therapy, including intravenous administration of glycerol.
We speculate that our patient likely had initial transient occlusion of the right vertebral artery at the origin of the right posterior inferior cerebellar artery, which probably gave rise to the bilateral medial branches of posterior inferior cerebellar arteries. This caused infarction in the territory of the medial branches on both sides without remaining brain stem signs. Such an unusual pattern of cerebellar infarction accompanied by acute hydrocephalus posed a diagnostic challenge at the time of transfer to our care, and correct diagnosis was facilitated by cranial magnetic resonance imaging.
Nitric oxide and the cerebral circulation.
Authors: Faraci F M , Brian J E 
Published: June 2011

Nitric oxide (NO) is a potent vasodilator that was initially described as the mediator of endothelium-dependent relaxation (endothelium-derived relaxing factor, EDRF). It is now known that NO is produced by a variety of other cell types.
Endothelium produces NO (EDRF) under basal conditions and in response to a variety of vasoactive stimuli in large cerebral arteries and the cerebral microcirculation. Endothelium-dependent relaxation is impaired in the presence of several pathophysiological conditions. This impairment may contribute to cerebral ischemia or stroke. Activation of glutamate receptors appears to be a major stimulus for production of NO by neurons. Neuronally derived NO may mediate local increases in cerebral blood flow during increases in cerebral metabolism. NO synthase-containing neurons also innervate large cerebral arteries and cerebral arterioles on the brain surface. Activation of parasympathetic fibers that innervate cerebral vessels produces NO-dependent increases in cerebral blood flow. Increases in cerebral blood flow during hypercapnia also appear to be dependent on production of NO. Astrocytes may release some NO constitutively, but astrocytes and microglia can release relatively large quantities of NO after induction of NO synthase in response to endotoxin or some cytokines. Expression of inducible NO synthase, perhaps in response to local production of cytokines, may exert cytotoxic effects in brain during or after ischemia.
Because endothelium, neurons, and glia can all produce NO in response to some stimuli, the influence of NO on the cerebral circulation appears to be very important. Under normal conditions, constitutively produced NO influences basal cerebral vascular tone and mediates vascular responses to a diverse group of stimuli. The inducible form of NO synthase produces much greater amounts of NO that may be an important mediator of cytotoxicity in brain.
Elevated serum cholesterol is a risk factor for both coronary heart disease and thromboembolic stroke in Hawaiian Japanese men. Implications of shared risk.
Authors: Benfante R , Yano K , Hwang L J , Curb J D , Kagan A , Ross W 
Published: June 2011

The relation between total serum cholesterol level and thromboembolic or nonhemorrhagic stroke is controversial. The Honolulu Heart Program cohort of Japanese-American men provides data which show that elevated serum cholesterol is an independent predictor of thromboembolic stroke as well as coronary heart disease (CHD). The data are presented to suggest that the association of elevated cholesterol with stroke is sometimes underestimated or underreported partly because of competing or shared risk with CHD, the other major atherosclerotic end point.
The data are based on 6352 men (aged 51 to 74 years) at baseline examination (1971 to 1974) who were free of clinical CHD and stroke and were followed an average of 15 years for new cases of both end points. Relative risks of serum cholesterol for CHD and thromboembolic stroke were calculated, controlling for other major cardiovascular covariates.
There was a continuous and progressive increase in both CHD and thromboembolic stroke rates with increasing levels of serum cholesterol. The relative risk between the highest and lowest quartiles of serum cholesterol was 1.7 (95% confidence interval, 1.4 to 2.0) for CHD and 1.4 (95% confidence interval, 1.1 to 1.9) for thromboembolic stroke. There was a decline in the difference in relative risks between CHD and thromboembolic stroke in older men (aged 60 years and older) compared with younger men (aged younger than 60 years).
These data provide additional evidence that elevated serum cholesterol should be considered a primary risk factor for thromboembolic stroke, presumably through its effect on both coronary and cerebrovascular atherosclerosis. It is suggested that this association is sometimes underestimated or underreported partly because of shared or competing risk with CHD, the clinical manifestation of atherosclerosis that generally occurs earlier in life and with greater frequency than thromboembolic stroke.
Comparison of carbon dioxide responsiveness of cerebellar blood flow between affected and unaffected sides with crossed cerebellar diaschisis.
Authors: Ishii K , Kanno I , Uemura K , Hatazawa J , Okudera T , Inugami A , Ogawa T , Fujita H , Shimosegawa E 
Published: June 2011

Concerning vasoreactivity of cerebellar blood flow (CeBF) in patients affected with crossed cerebellar diaschisis (CCD), several controversies have been reported. One is reduced asymmetry of CeBF after acetazolamide administration in 99mTc hexamethylpropyleneamine oxime single-photon emission-computed tomography, and the other is persistent asymmetry with alternation in PaCO2 using the 133Xe clearance method. The purpose of this study is to examine whether CeBF vasoreactivity in the side affected with CCD is the same as that in the unaffected side.
We analyzed CeBF during hypocapnia, normocapnia, and hypercapnia performed in 27 patients with cerebrovascular disease (age range, 38 to 73 years; mean age, 62.0 +/- 8.5 years) affected by CCD. CeBF was measured using H2(15)O and positron emission tomography.
The CeBF ratio of CCD-affected side to CCD-unaffected side was consistent during the perturbation of PaCO2. This ratio was 0.82 +/- 0.08 for PaCO2 elevation and 0.83 +/- 0.07 for PaCO2 lowering. Both were not significantly different from unity.
The percent change of CeBF per millimeter of mercury PaCO2 change was uniform across affected and unaffected sides with CCD. These findings are consistent with our recent findings observed in activated cerebral tissue during photic stimulation.
p53-immunoreactive protein and p53 mRNA expression after transient middle cerebral artery occlusion in rats.
Authors: Li Y , Chopp M , Zhang Z G , Zaloga C , Niewenhuis L , Gautam S 
Published: June 2011

We investigated the temporal distribution of the p53-immunoreactive protein in conjunction with cellular damage and the expression of the p53 mRNA after focal cerebral ischemia in rats.
Male Wistar rats (n = 66; controls, n = 7) were subjected to 2 hours of middle cerebral artery occlusion and were killed at various times of reperfusion (0.5 to 168 hours) for p53 immunohistochemistry and Northern blot analysis.
A cellular expression of mutant p53-immunoreactive protein was found localized to anatomic sites exhibiting severe neuronal damage. A maximal induction of mutant p53-immunoreactive protein was found at 12 hours after reperfusion and subsequently declined. No wild-type p53 protein expression was detected after ischemia. A time-dependent expression of p53 mRNA was observed in both hemispheres. The peak level of p53 mRNA occurred at 24 hours after reperfusion.
Our data indicate that the expressions of p53-immunoreactive protein and p53 mRNA are upregulated after transient focal cerebral ischemic insult in rats. The concomitant appearance of p53 and cell damage in ischemic brain suggests that p53 expression may impact cell biological response to an ischemic insult.
Chronic cerebral hypoperfusion and impaired neuronal function in rats.
Authors: Sekhon L H , Morgan M K , Spence I , Weber N C 
Published: June 2011

Studies in acute cerebral ischemia have shown that reductions in cerebral blood flow of up to 50% do not lead to infarction or alterations in neuronal electric activity. Little is known about the effects of chronic reductions in cerebral blood flow. The purpose of this study was to evaluate neuronal electrophysiological function in brain that had been subjected to a chronic reduction of cerebral blood flow of less than 50%. Based on existing knowledge of thresholds of cerebral ischemia, neuronal electrophysiological function should be unaffected by hypoperfusion of this magnitude.
An arteriovenous fistula model in the rat was used to induce chronic cerebral hypoperfusion with reductions of cerebral blood flow of 25% to 50% as measured previously by 14C-labeled autoradiography. Using in vitro electrophysiological brain slice techniques, long-term potentiation in hippocampal CA1 neurons was examined extracellularly after 6 months of chronic noninfarctional cerebral hypoperfusion. Brains were also examined histologically at this time for evidence of cerebral infarction.
There was no evidence of cerebral infarction. Long-term potentiation was produced in 9 of 12 control animals and only 2 of 8 hypoperfused animals. This difference was significant (P < .05) and demonstrated that long-term potentiation was impaired in animals with chronic hypoperfusion.
Noninfarctional reductions in cerebral blood flow of up to 50% do impair neuronal function in chronic cerebral ischemia, a result quite distinct from that seen in acute ischemia. The threshold for neuronal dysfunction in chronic cerebral hypoperfusion is lower than that found in acute cerebral ischemia, suggesting that duration as well as severity of ischemic insult determines cellular viability. Chronic hypoperfusion may lead to a noninfarctional state with impaired neuronal function, a category of chronic cerebral ischemia not previously identified.
Cortical hypoperfusion after global forebrain ischemia in rats is not caused by microvascular leukocyte plugging.
Authors: Dirnagl U , Niwa K , Sixt G , Villringer A 
Published: June 2011

We tested the hypothesis that cerebral hypoperfusion after experimental global cerebral ischemia is caused by plugging of the microcirculation with activated leukocytes using in vivo microscopic observation of the behavior of leukocytes in the cortical microcirculation during the transition from postischemic hyperperfusion to hypoperfusion.
Anesthetized and ventilated rats (n = 24) were equipped with a closed cranial window. Physiological variables and cortical regional cerebral blood flow (laser-Doppler flowmetry) were measured continuously. Leukocytes were labeled intravitally with rhodamine 6G and visualized in the microcirculation of the brain surface and outer layers of the cortex with confocal laser scanning microscopy from preischemia to 4 hours after reperfusion that followed 10 minutes of global cerebral ischemia (rCBF < 10% of control).
In controls (n = 8), there were no signs of leukocyte activation over the 4-hour observation period. In ischemic rats (n = 16), during the transition from hyperperfusion to hypoperfusion there was no change in the behavior of leukocytes. Most notably, no capillary pluggers were seen. In the postischemic period only a slight increase of the number of leukocytes rolling along or sticking to the venular endothelium was seen, and very few capillaries were plugged by leukocytes. Extravasation of leukocytes into the brain tissue was observed in 8 rats beginning 2 hours after ischemia with a variable degree between animals.
Because there was only mild activation of leukocyte-endothelium interaction within the first hours of reperfusion after 10 minutes of global forebrain ischemia, because no leukocytes plugged superficial cortical capillaries during the transition from hyperperfusion to hypoperfusion, and because the regional cerebral blood flow transition was very rapid, we speculate that leukocyte plugging is not responsible for the early cortical hypoperfusion seen after brief global ischemia in rats.
Tryptophan hydroxylase activity in rat brain base arteries related to innervation originating from the dorsal raphe nucleus.
Authors: Moreno M J , López de Pablo A L , Marco E J 
Published: June 2011

Tryptophan hydroxylase activity was assayed in cell-free extracts of rat brain base arteries as marker of a serotonergic innervation.
Estimation of the enzymatic activity was made in untreated male Sprague-Dawley rats (n = 53) and in those who underwent destruction of the dorsal and median raphe nuclei (n = 10).
Tryptophan hydroxylase activity was measured in rat cerebral arteries. The time-dependent 5-hydroxytryptophan production was undetectable in the absence of tryptophan or 6-methyltetrahydropterine and in the presence of 6-fluorotryptophan, and it was significantly reduced in the presence of p-chlorophenylalanine. Destruction of the dorsal raphe nucleus but not the median raphe nucleus brought about a significant reduction in enzyme activity.
These results suggest that rat cerebral arteries receive a serotonergic innervation arising from the dorsal raphe nucleus.
Pathoanatomic correlation between poststroke pathological crying and damage to brain areas involved in serotonergic neurotransmission.
Authors: Andersen G , Ingeman-Nielsen M , Vestergaard K , Riis J O 
Published: June 2011

The aim of the study was to correlate the severity of poststroke pathological crying with lesion size and location.
Twelve selected stroke patients were ranked in terms of overall clinical severity of the syndrome of pathological crying, and the size and location of the stroke lesion(s) were determined by magnetic resonance imaging.
The patients with the clinically most severe pathological crying had relatively large bilateral pontine lesions without lesions in the hemispheres. The intermediate group had bilateral central hemispheric lesions, and the clinically least affected patients had mainly unilateral large subcortical lesions.
Poststroke pathological crying may be attributable to stroke-induced partial destruction of the serotonergic raphe nuclei in the brain stem or their ascending projections to the hemispheres.