bluuebunny/crossref_metadata_2025 huggingface dataset:
Residual lesions on computed tomography after intracerebral hemorrhage.
Authors: Franke C L , van Swieten J C , van Gijn J
Published: June 2011

We investigated the residual abnormalities on computed tomography in a series of patients with proven intracerebral hemorrhage to determine whether the type of lesion is related to the site and size of the initial hematoma.

In a partially prospective follow-up study, we studied computed tomographic scans of 42 patients with spontaneous intracerebral hemorrhage after 2-24 (median 9) months.

Lobar hemorrhages had occurred in 20 patients; the other 22 hemorrhages were in the basal ganglia or thalamus. No residual lesions were found on seven scans (17%), despite residual handicap in three of these seven patients (slight, moderate, and moderately severe). In five cases, the scan showed only focal atrophy, and in two there were only focal calcifications. There were six patients with slit-like lesions (only after deep hemorrhages), 12 with rounded and isolated hypodense areas, and 10 with rounded hypodense areas connected to the ventricular system. The connection between the residual lesion and the ventricular system depended to a large extent on the size of the initial hematoma, but very little on whether it had initially ruptured into the ventricular system.

A retrospective diagnosis of cerebral hemorrhage on radiological grounds can be made with confidence only in a small group of patients with slit-like lesions in the basal ganglia. This diagnosis is impossible in approximately one third of cerebral hemorrhages because the abnormalities are aspecific or have completely disappeared.
Platelets augment rabbit cerebral artery constriction by activating protein kinase C.
Authors: Germann P , Laher I , Bevan J A
Published: June 2011

We tested the hypothesis that activated platelets augment cerebral artery responsiveness to thrombin by activating protein kinase C, a possible intracellular modulator of Ca2+ sensitivity.

Ring segments of rabbit basilar artery were prepared for in vitro measurements of isometric force. Cumulative concentration-response curves to thrombin were made in the absence or presence of activated platelets.

Arteries contracted to thrombin in a concentration-dependent manner; freshly obtained human platelets (8.5 x 10(8) cells/ml) activated with 10 micrograms/ml collagen increased the arteries' sensitivity to thrombin by threefold while augmenting the maximal response from 40 +/- 11% to 66 +/- 12% of the maximal response to 0.3 mM histamine. At 10 nM, staurosporine, an inhibitor of protein kinase C activity, blunted the platelet-induced augmentation of the response to thrombin but did not alter the sensitivity or the maximal contraction to 8-64 mM K+. Removal of the endothelium did not alter the characteristics of the thrombin concentration-response curve. The addition of activated platelets increased the tissue sensitivity of endothelium-denuded arteries to thrombin by a factor of 30, and the maximal response to thrombin was 101 +/- 27% of the histamine response.

Our findings suggest that amplification of the arterial contractile response to thrombin caused by platelet-derived mediators may be due to activation of protein kinase C. There may also be a protective role for the cerebrovascular endothelium since endothelium reduced the extent of augmentation of protein kinase C-mediated tone by vasoactive agents released by activated platelets. Thus, increased vascular responsiveness caused by activated platelets may in part be due to protein kinase C-mediated changes in the intracellular sensitivity to Ca2+.
Neurochemical analysis of focal ischemia in rats.
Authors: Uemura Y , Miller J M , Matson W R , Beal M F
Published: June 2011

Increases in uric acid follow experimental stroke, which may be related to free radical formation by xanthine oxidase. The present study examined the time course of changes in xanthine and uric acid and their relationship to changes in the free radical scavengers glutathione, cysteine, and ascorbic acid.

Focal ischemia was induced by occluding the middle cerebral artery, followed by transient occlusion of the common carotid arteries for 60 minutes. At varying time points, animals were sacrificed, and ischemic cortex was dissected. Neurochemical measurements were made by high-performance liquid chromatography with 16-sensor electrochemical detection.

Marked increases in uric acid were seen at all time points, with a maximal increase at 1 day and a persistent increase lasting up to 21 days. There were smaller reciprocal decreases in xanthine. Glutathione, cysteine, and ascorbic acid showed significant decreases, consistent with the generation of free radicals. Reductions in levels of cysteine and glutathione were significantly correlated with increases in uric acid levels.

These findings confirm marked alterations in purine metabolism following focal ischemia and suggest that xanthine oxidase contributes to the generation of free radicals.
Mortality in acute stroke with atrial fibrillation. The Italian Acute Stroke Study Group.
Authors: Candelise L , Pinardi G , Morabito A
Published: June 2011

We compared 211 consecutive patients who had acute ischemic hemispheric stroke and atrial fibrillation with 837 consecutive patients who had stroke without atrial fibrillation. The atrial fibrillation group included a higher frequency of women, older subjects, and those with a severe neurologic deficit, abnormal computed tomogram, and elevated heart rate. The 1-month case-fatality rate in the atrial fibrillation group was 27% while that in the group without atrial fibrillation was 14%. The 6-month case-fatality rates in the two groups were 40% and 20%, respectively. The risk of death attributable to atrial fibrillation, adjusted for the effect of other prognostic factors, was significant at 1 month (relative risk = 1.55) and at 6 months (relative risk = 1.74). The causes of death were equally distributed in the two groups during both the acute and subacute phases. We conclude that atrial fibrillation is a negative prognostic factor in patients hospitalized for acute stroke. Nevertheless, cerebral embolism alone does not completely explain the increase in mortality for stroke patients with atrial fibrillation. Other associated pathogenetic mechanisms must also be taken into account.
Babinski-Nageotte syndrome on magnetic resonance imaging.
Authors: Nakane H , Okada Y , Sadoshima S , Fujishima M
Published: June 2011

A 70-year-old woman developed left hypoglossal nerve palsy, a right hemiparesis sparing the face, and a typical left Wallenberg's syndrome. These symptoms resulted from a lesion in the left half of the medulla oblongata, suggesting Babinski-Nageotte syndrome, a rare cerebrovascular disease. This is the first case of ischemic infarction in the territory of the left vertebral artery and posterior inferior cerebellar artery demonstrated on magnetic resonance imaging. Severe bilateral lesions of the distal vertebral arteries demonstrated on digital subtraction angiography may have contributed to the development of this syndrome.
Pathways of parasympathetic and sensory cerebrovascular nerves in monkeys.
Authors: Hardebo J E , Arbab M , Suzuki N , Svendgaard N A
Published: June 2011

Using immunohistochemistry, we studied the origins and pathways of parasympathetic and sensory nerve fibers to the pial arteries in four squirrel monkeys. Following its application to the surface of the middle cerebral artery, the retrograde axonal tracer True Blue accumulated in parasympathetic neurons of the sphenopalatine ganglion and the internal carotid ganglion. The latter is strategically located where the internal carotid artery enters the cranium. Fibers from the sphenopalatine ganglion reach the internal carotid artery in the cavernous sinus region after running as rami orbitales. Before reaching the internal carotid artery, the fibers bypass aberrant sphenopalatine ganglia, with the most distant, the cavernous ganglion, being located in the cavernous sinus region. True Blue also accumulated in sensory neurons of the ophthalmic and maxillary divisions of the trigeminal ganglion and in sensory neurons of the internal carotid ganglion. Fibers from the ophthalmic division of the trigeminal ganglion reach the internal carotid artery as a branch through the cavernous sinus, bypassing the cavernous ganglion. Fibers from the maxillary division also bypass the cavernous ganglion after reaching it via a recurrent branch of the orbitociliary nerve. Thus, the cavernous ganglion forms a confluence zone for parasympathetic and sensory fibers in the region. In addition, parasympathetic and sensory fibers leave the confluence zone to follow the abducent and trochlear nerves backward to the basilar artery and tentorium cerebelli, respectively. Clinical implications are discussed.
Effects of tirilazad mesylate on postischemic brain lipid peroxidation and recovery of extracellular calcium in gerbils.
Authors: Hall E D , Pazara K E , Braughler J M
Published: June 2011

We describe the effects of the 21-aminosteroid tirilazad mesylate (U-74006F) on postischemic lipid peroxidation (depletion of brain vitamin E) and cortical extracellular calcium recovery in gerbils subjected to 3 hours of unilateral carotid artery occlusion. Male gerbils were treated with either 0.2 ml vehicle (0.05N HCl) or 10 mg/kg i.p. U-74006F 10 minutes before the induction of ischemia and again immediately after the initiation of reperfusion. In the first series of experiments, the brain concentration of vitamin E, which was unaffected by ischemia without reperfusion, was decreased after 2 hours of reperfusion by an average of 60% in vehicle-treated animals compared with sham-operated animals; in the U-74006F-treated gerbils, the 2-hour postischemic vitamin E loss was only 27% (p less than 0.002 different from vehicle-treated animals). In the second series, unilateral carotid artery occlusion produced a decrease in the cortical extracellular calcium concentration from 1.05 mM before ischemia to 0.11 mM by the end of the ischemic episode in both vehicle- and U-74006F-treated gerbils. After 2 hours of reperfusion, the calcium concentration had recovered to only 0.22 mM in the vehicle-treated animals compared with 0.56 mM in the U-74006F-treated group (p less than 0.01). Cortical blood flow, mean arterial blood pressure, and blood gases did not differ significantly between the two treatment groups. Administration of only the immediate postreperfusion dose (i.e., no pretreatment) also significantly improved the recovery of cortical extracellular calcium. The results indicate that U-74006F inhibits postischemic lipid peroxidation as assessed by the preservation of brain vitamin E and that, secondary to this membrane-protective effect, the processes responsible for the reversal of ischemia-triggered intracellular calcium accumulation are preserved.
Cerebrovascular CO2 reactivity during delayed vasospasm in a canine model of subarachnoid hemorrhage.
Authors: Diringer M N , Heffez D S , Monsein L , Kirsch J R , Hanley D F , Traystman R J
Published: June 2011

While the in vitro reactivity of cerebral conducting vessels following subarachnoid hemorrhage has been extensively studied, in vivo cerebrovascular CO2 reactivity has not been systematically investigated. We tested the hypothesis that, in the canine model of subarachnoid hemorrhage, the rise in cerebral blood flow normally seen with hypercapnia is blunted during delayed vasospasm. Four groups of animals were studied: one received two 4-ml subarachnoid injections of nonheparinized arterial blood into the cisterna magna (n = 8), one received three subarachnoid injections of 5 ml blood (n = 5), one received two subarachnoid injections of 4 ml saline (n = 5), and a control group (n = 5) had no subarachnoid injections or angiography. Basilar artery diameter was measured from baseline and follow-up angiography. We determined CO2 reactivity by randomly varying the concentration of inspired CO2 and measuring regional cerebral blood flow with radiolabeled microspheres. Basilar artery diameter was not affected by saline injection and was reduced by 26 +/- 2.9% in the two-hemorrhage group and 55 +/- 1.9% in the three-hemorrhage group. Baseline cerebral blood flow and CO2 reactivity were similar in all four groups. We conclude that, in this model of delayed vasospasm, regional cerebral vascular CO2 reactivity is intact and extrapolation of in vitro data regarding basilar artery diameter and reactivity to cerebral blood flow must be done cautiously.
Cerebral venous thrombosis with plasminogen deficiency.
Authors: Schutta H S , Williams E C , Baranski B G , Sutula T P
Published: June 2011

We describe a patient with inherited plasminogen deficiency who developed extensive cerebral venous thrombosis. Several other conditions that might have contributed to a hypercoagulable state, including mild thrombocytosis, thyrotoxicosis, and a chronic inflammatory lung disorder, were present. We also discuss the evidence linking plasminogen deficiency with a thrombophilic state. The diagnosis of cerebral venous thrombosis in this case was readily established by nuclear magnetic resonance imaging, a technique that is ideally suited for the evaluation and follow-up of patients with this condition.
Stroke after heavy marijuana smoking.
Authors: Zachariah S B
Published: June 2011

I examined two young men who developed cerebral infarction associated with heavy marijuana smoking. Both were light tobacco smokers, but they did not drink alcohol or use other street drugs. Diagnostic work-up for nonatherosclerotic causes of stroke was unremarkable. I postulate that marijuana-associated alterations in systemic blood pressure resulted in vasospasm, leading to strokes in these patients.
Early treatment of ischemic stroke with a calcium antagonist.
Authors: Rosenbaum D , Zabramski J , Frey J , Yatsu F , Marler J , Spetzler R , Grotta J
Published: June 2011

We performed a feasibility and safety study (phase II) of nicardipine, a calcium antagonist, in 57 patients. The objectives of the study were to begin therapy as early as possible (less than or equal to 12 hours) after the onset of ischemic stroke and to administer as high a dose as possible. All patients received an intravenous infusion of nicardipine for 72 hours, starting with a dose of 3 mg/hr and increasing to a maximum dose of 7 mg/hr. Upward titration of the dose was limited by a 10% decrease in blood pressure or a 20 beats/min increase in pulse. Intravenous therapy was followed by 30 days of oral therapy. The mean +/- SD interval from onset of stroke to commencement of therapy was 9.1 +/- 5.4 hours. Adverse reactions consisted primarily of hypotension requiring discontinuation of therapy in four patients. Score on a graded neurologic examination increased from 41/100 at baseline to 64/100 at 3 months for the 41 patients completing follow-up. There was no correlation between the dose of nicardipine administered and outcome, but the 11 patients starting therapy less than or equal to 6 hours after onset did better than those starting therapy 6-12 hours after onset. Further study of very early therapy with nicardipine is justified.
Nuclear magnetic resonance spectroscopy study of human brain after cardiac resuscitation.
Authors: Martin G B , Paradis N A , Helpern J A , Nowak R M , Welch K M
Published: June 2011

We used 31P nuclear magnetic resonance spectroscopy to study the cerebral metabolic function of eight patients with severe postischemic anoxic encephalopathy secondary to cardiac arrest. Spectroscopy was performed at 18 +/- 13 and 64 +/- 20 hours after resuscitation. Glasgow Coma Scale scores at the time of initial and repeat spectroscopy were 3.6 +/- 1.2 and 3.5 +/- 1.2, respectively. In those patients whose spectra were of adequate quality to monitor pH, all demonstrated tissue alkalosis in at least one brain region. The mean brain pH at initial spectroscopy was 7.14 +/- 0.09 and was significantly alkalotic when compared with age- and sex-matched normal controls (pH = 6.98 +/- 0.04, p less than 0.0001). Five of the eight patients showed at least one region of persistent alkalosis at repeat spectroscopy, whereas one patient demonstrated severe acidosis with a pH of 6.42. Spectra demonstrated marked metabolic heterogeneity, ranging from normal in appearance to complete obliteration of all high-energy phosphates with only inorganic phosphate remaining.
Brain polyphosphoinositide metabolism during focal ischemia in rat cortex.
Authors: Lin T N , Liu T H , Xu J , Hsu C Y , Sun G Y
Published: June 2011

Using a rat model of stroke, we examined the effects of focal cerebral ischemia on the metabolism of polyphosphoinositides by injecting 32Pi into both the left and right cortices. After equilibration of the label for 2-3 hours, ischemia induced a significant decrease (p less than 0.001) in the concentrations of labeled phosphatidyl 4,5-bisphosphates (66-78%) and phosphatidylinositol 4-phosphate (64-67%) in the right middle cerebral artery cortex of four rats. The phospholipid labeling pattern in the left middle cerebral artery cortex, which sustained only mild ischemia and no permanent tissue damage, was not different from that of two sham-operated controls. However, when 32Pi was injected 1 hour after the ischemic insult, there was a significant decrease (p less than 0.01) in the incorporation of label into the phospholipids in both cortices of four ischemic rats compared with four sham-operated controls. Furthermore, differences in the phospholipid labeling pattern were observed in the left cortex compared with the sham-operated controls. The change in labeling pattern was attributed to the partial reduction in blood flow following ligation of the common carotid arteries. We provide a sensitive procedure for probing the effects of focal cerebral ischemia on the polyphosphoinositide signaling pathway in the brain, which may play an important role in the pathogenesis of tissue injury.
Factors influencing admission blood pressure levels in patients with acute stroke.
Authors: Carlberg B , Asplund K , Hägg E
Published: June 2011

In clinical practice, patients with acute stroke often have high blood pressure. The aim of this study was to investigate factors correlated with blood pressure elevation in 843 consecutive stroke patients on hospital admission to a nonintensive stroke unit. Using a multivariate analysis model, we analyzed the influence on admission blood pressure of sex, age, previous hypertension, cardiac failure, diabetes, type of stroke, impaired consciousness, and latency between onset of symptoms and admission. Previous hypertension was the strongest predictor (p less than 0.001) of elevated blood pressure on admission, followed by the presence of intracerebral hemorrhage (p less than 0.001). The latency between onset of symptoms and admission showed no correlation with blood pressure levels at hospitalization. Previously, high blood pressure levels on hospital admission have been shown to decline within a few days in hospital. We therefore hypothesize that mental stress on hospital admission may be a major factor in the blood pressure elevation seen in acute stroke.
Changing rates of stroke in the province of Quebec, Canada: 1981-1988.
Authors: Mayo N E , Goldberg M S , Levy A R , Danys I , Korner-Bitensky N
Published: June 2011

Using more than 37,000 hospital discharges attributed to hemorrhagic or occlusive stroke in the province of Quebec, Canada, we analyzed trends in stroke incidence during the period 1981-1988. There were large and statistically significant (p less than 0.05) increases in the rates of hemorrhagic stroke over this period. Dramatic increases occurred among men in the rates of both intracerebral (International Classification of Diseases--Ninth Revision [ICD9] code 431) and intracranial (ICD9 code 432) hemorrhagic strokes (40-204% depending on age). In contrast, the rates of occlusion of the precerebral arteries (ICD9 code 433) declined in younger men and women but increased substantially (107%) in older men. Rates of occlusion of the cerebral arteries (ICD9 code 434) declined in men over the age of 50 years and in women aged 50-79 years. Despite the decline in the rate of occlusion of the cerebral arteries, the rate of hemorrhagic stroke appears to have increased. Changes in the hospitalization rates for hemorrhagic stroke were not accompanied by consistent decreases in the case-fatality rate. This finding tends to support the hypothesis of an actual increase in the hospitalization rate fo hemorrhagic stroke rather than an artifactually elevated rate due to enhanced diagnosis by computed tomography.
Leukoaraiosis correlates with cerebral hypoperfusion in vascular dementia.
Authors: Kawamura J , Meyer J S , Terayama Y , Weathers S
Published: June 2011

Leukoaraiosis quantified by computerized densitometric measurements of reduced Hounsfield numbers was correlated with local cerebral blood flow on the same computed tomographic images of 35 patients with multi-infarct dementia and 16 age-matched elderly normal volunteers. The ratio for area of frontal leukoaraiosis to total area of parenchyma among the patients was significantly greater than that among the normal volunteers (5.8 +/- 2.3% compared with 3.1 +/- 1.3%, p less than 0.001). Severity of leukoaraiosis around the frontal horns of the lateral ventricles correlated significantly with severity of leukoaraiosis of the centrum semiovale adjacent to the bodies of the lateral ventricles. Cerebral blood flow values for all representative cerebral regions except the parietal white matter were reduced among the patients compared with the normal volunteers. Multivariate regression analysis revealed that reduced cerebral perfusion in the putamen and thalamus correlated significantly with the severity of leukoaraiosis. Cerebral hypoperfusion in territories supplied by deep penetrating arteries may contribute to the pathogenesis of leukoaraiosis.
Effect of recirculation on exacerbation of ischemic vascular lesions in rat brain.
Authors: Nishigaya K , Yoshida Y , Sasuga M , Nukui H , Ooneda G
Published: June 2011

Using electron microscopy, we investigated the small arteries and veins in ischemic lesions induced by occlusion of the ostium of the middle cerebral artery in 42 rats. We observed endothelial denudation in the small arteries of rats receiving occlusion for greater than 6 hours. When the occluding cylinder was removed to allow for reperfusion, however, 2 hours of occlusion was sufficient for endothelial denudation to occur. Medial smooth muscle cells seemed to be more vulnerable to ischemia than endothelial cells because ultrastructural changes in the former cells preceded endothelial denudation. Moreover, endothelial denudation definitely exacerbated vascular changes so that medial necrosis appeared to be complete beneath the denuded areas, allowing erythrocytes, platelets, and exogenous tracers to penetrate into the cytoplasm of smooth muscle cells. These arterial lesions seemed to be repaired 10 days after removal of the occluding cylinder following 2 hours of occlusion. On the other hand, small veins in the ischemic lesion did not show endothelial denudation or medial necrosis. Our study suggests that arterial changes in ischemic lesions play a role in exacerbating the brain edema caused by recirculation after ischemia.
Polyethylene glycol-conjugated superoxide dismutase fails to augment brain superoxide dismutase activity in piglets.
Authors: Haun S E , Kirsch J R , Helfaer M A , Kubos K L , Traystman R J
Published: June 2011

We studied the effect of intravenously administered polyethylene glycol-conjugated superoxide dismutase (8,000 units/kg) on brain superoxide dismutase activity in 44 1-2-week-old piglets in the absence and presence of global cerebral ischemia and reperfusion. Four groups (n = 6 each) of piglets not exposed to ischemia were studied. Enzyme administration increased plasma superoxide dismutase activity from less than 5 to 142 +/- 8 units/ml (mean +/- SEM) without increasing brain activity (e.g., activities in the caudate were 7.9 +/- 0.5 and 8.1 +/- 0.4 units/mg protein) for up to 2 hours following administration. Four additional groups (n = 5 each) of piglets were given either enzyme or polyethylene glycol 5 minutes prior to 10 minutes of global cerebral ischemia induced by aortic cross-clamping followed by either 5 or 45 minutes of reperfusion. Enzyme administration increased plasma superoxide dismutase activity from less than 5 to 144 +/- 5 units/ml but failed to increase brain activity even after 45 minutes of reperfusion (e.g., activities in the caudate were 8.5 +/- 0.3 and 8.6 +/- 0.6 units/mg protein). We conclude that intravenous polyethylene glycol-conjugated superoxide dismutase does not increase superoxide dismutase activity in the brain despite global ischemia and reperfusion.
Enhanced detection of intracardiac sources of cerebral emboli by transesophageal echocardiography.
Authors: Lee R J , Bartzokis T , Yeoh T K , Grogin H R , Choi D , Schnittger I
Published: June 2011

We performed transesophageal echocardiography in 50 consecutive hospitalized patients with recent transient ischemic attack or stroke of embolic origin to determine whether transesophageal echocardiography is more sensitive than transthoracic echocardiography in detection of possible intracardiac sources of embolism. Twenty-six of 50 patients with a negative transthoracic echocardiogram for potential source of emboli had a transesophageal echocardiography study that demonstrated at least one intracardiac abnormality. Abnormalities noted by transesophageal echocardiography included five of 50 patients with either a left atrial or left atrial appendage clot, four patients with a patent foramen ovale, and nine patients with spontaneous echocardiographic contrast. In 11 of 50 patients with no other source of embolism, we found highly mobile filamentous strands on the mitral valve, which have not been described previously. These mitral valve echo strands may represent a fissured surface or fibrosis that can serve as a nidus for thrombus formation. We detected no unexpected left ventricular thrombus or left atrial myxoma. Factors significantly associated with a greater likelihood of a positive transesophageal echocardiography study included left atrial enlargement, atrial fibrillation, and a calcified or thickened mitral valve. Our study suggests that transesophageal echocardiography is a valuable addition to transthoracic echocardiography in investigating potential intracardiac sources of embolism.
Antiphospholipid antibodies in cerebral ischemia.
Authors: Montalbán J , Codina A , Ordi J , Vilardell M , Khamashta M A , Hughes G R
Published: June 2011

In a 2-year prospective study of 146 patients with cerebral ischemia, we compared vascular risk factors for stroke with clinical and laboratory findings, particularly antiphospholipid antibodies. Ten patients (6.8%) were positive for at least one antiphospholipid antibody; one patient had systemic lupus erythematosus, one had rheumatoid arthritis, and the remaining eight fulfilled criteria for the diagnosis of primary antiphospholipid syndrome. These patients were predominantly male, not necessarily young, and 50% of them did not have any other vascular risk factors; there were no significant clinical or paraclinical differences between these patients and those without antiphospholipid antibodies. Outcome in the 10 patients was good, and platelet antiaggregating drugs proved to be useful in preventing further cerebrovascular ischemic events in our patients.
Role of the basilar artery in regulation of blood flow to the brain stem in rats.
Authors: Fujii K , Heistad D D , Faraci F M
Published: June 2011

Large arteries contribute to the regulation of cerebral blood flow. The goal of this study was to examine the effects of changes in diameter of the basilar artery on blood flow to the brain stem. We measured blood flow with laser-Doppler flowmetry in anesthetized rats. The topical application of 10(-6) M serotonin, which selectively constricts large arteries, reduced diameter of the basilar artery by 47 +/- 5% (mean +/- SEM, n = 6) but did not alter blood flow to the ventral brain stem (change in blood flow -2 +/- 5%). The topical application of 10(-8) M vasopressin, which affects both large and small vessels, decreased blood flow by 33 +/- 4% (n = 6). In rats with spontaneous vasomotion, the basilar artery showed rhythmic changes in diameter at a frequency of 4.0 +/- 0.1 cycles/min and an amplitude of 20 +/- 1% of mean diameter (n = 6). Blood flow to the ventral brain stem cycled at the same frequency as and in phase with changes in diameter of the basilar artery, with an amplitude of 15 +/- 1%. We conclude that constriction of the basilar artery may occur with no change in brain stem perfusion. The distinct changes in blood flow during spontaneous vasomotion suggest that vasomotion occurs in intraparenchymal arterioles as well as in the basilar artery.
Intracarotid saline infusion improves outcome from incomplete ischemia in rats.
Authors: Hoffman W E , Ferguson L , Thomas C , Albrecht R F
Published: June 2011

Previous studies suggest that rheological changes associated with ischemia may produce postischemic hypoperfusion. We tested whether intracarotid or intravenous infusions of saline improve neurological outcome from incomplete cerebral ischemia in rats. Rats were anesthetized with 1.4% isoflurane in air, and ischemia was produced by unilateral carotid artery ligation combined with hemorrhagic hypotension to 30 mm Hg for 30 minutes. Intracarotid (n = 10) or intravenous (n = 10) saline infusion (0.3 ml/min) decreased hematocrit 20% compared with control rats (n = 10). Neurological outcome was significantly improved in rats infused with intracarotid (p less than 0.05) but not intravenous saline during ischemia without a change in brain temperature. Cerebral blood flow, measured in a separate study using laser Doppler flowmetry (n = 5), decreased 70% (p less than 0.01) during carotid ligation and hypotension but was not changed by intracarotid saline infusion (p greater than 0.30). These results show that perfusion of ischemic brain with saline improves outcome by factors not related to changes in hematocrit, brain temperature, or intraischemic tissue blood flow.
Temporal evolution of ischemic damage in rat brain measured by proton nuclear magnetic resonance imaging.
Authors: Knight R A , Ordidge R J , Helpern J A , Chopp M , Rodolosi L C , Peck D
Published: June 2011

We studied the effect of focal cerebral ischemia on the "state" of brain water using proton nuclear magnetic resonance imaging. Focal cerebral ischemia was induced in five halothane-anesthetized rats via tandem occlusion of the left common carotid artery and the left middle cerebral artery. The proton transverse relaxation time, the proton density, and the water diffusion coefficient were measured at various times from the same region of brain tissue from 1.5 to 168 hours after occlusion. Early measurements indicated significant changes in the transverse relaxation time (p = 0.004) and water diffusion coefficient (p = 0.002) of ischemic brain tissue compared with a homologous region from the contralateral hemisphere. However, the transverse relaxation time, proton density, and water diffusion coefficient in ischemic brain tissue showed different temporal evolutions over the study period. Diffusion coefficient weighting was superior to relaxation time and proton density weighting for the visualization of early cerebral ischemia. Our data suggest that nuclear magnetic resonance imaging is sensitive in detecting changes in proton-associated parameters during early cerebral ischemia and confirm significant changes (p less than or equal to 0.01) in the temporal evolution of transverse relaxation times, proton densities, and diffusion coefficients following middle cerebral artery occlusion.
Clinical anatomic study of pure dysarthria.
Authors: Ichikawa K , Kageyama Y
Published: June 2011

Nine patients with pure dysarthria underwent computed tomography or magnetic resonance imaging. Eight patients had infarcts of lacunar or larger size in the internal capsule: four in the superior portion of the anterior limb or adjacent corona radiata and four in the superior portion of the genu or the adjacent corona radiata. In one patient, there was a small infarct in the bulbar motor cortex. Dysarthria was transient and characterized by poor articulation in all cases. Five patients also had contralateral facial weakness, and three patients with lesions in the genu had minimal and transient involvement of the contralateral fingers. These three cases appeared to be variants of the dysarthria-clumsy hand syndrome. We submit that this syndrome should sometimes be regarded as a stroke syndrome rather than always as a lacunar syndrome.
Effect of antihypertensive therapy on focal stroke in spontaneously hypertensive rats.
Authors: Slivka A
Published: June 2011

Spontaneously hypertensive rats subjected to focal cerebral ischemia develop larger infarcts than normotensive rat strains. To determine whether antihypertensive therapy decreases infarct volume in hypertensive rats, 60 13-week-old animals were treated with 20 mg/kg hydralazine added daily to the drinking water for 1.5, 6, 10, or 16 weeks and then subjected to focal cerebral ischemia by tandem right common carotid artery and middle cerebral artery occlusion. Blood pressure in the treated groups was substantially lower than that in untreated groups after 1 week of hydralazine therapy and remained lower for the entire treatment period in all four experiments. Mean infarct volume in spontaneously hypertensive rats treated for 10 (p = 0.02) or 16 (p = 0.005) weeks, but not 1.5 or 6 weeks, was significantly less than that in the untreated controls. The percentage reduction of infarct volume in animals treated for 10 and 16 weeks was similar. This study demonstrates that antihypertensive therapy decreases infarct volume in hypertensive rats subjected to focal cerebral ischemia. This treatment effect appears to be dependent on the duration of therapy, and the magnitude of the treatment effect seems to plateau by 10 weeks of therapy.
Benefit of a stroke unit: a randomized controlled trial.
Authors: Indredavik B , Bakke F , Solberg R , Rokseth R , Haaheim L L , Holme I
Published: June 2011

In a randomized controlled trial we compared the clinical outcome of acute stroke patients, 110 of whom were allocated to treatment in a stroke unit and 110 to treatment in general medical wards. No significant difference existed between these groups with regard to sex, age, marital status, medical history, or functional impairment on admission. Outcome was measured at 6 and 52 weeks after the stroke by the proportion of patients at home, the proportion of patients in an institution, the mortality, and the functional state. After 6 weeks 56.4% of the patients randomized to the stroke unit and 32.7% of the patients randomized to the general medical wards were at home (p = 0.0004), and after 52 weeks 62.7% and 44.6%, respectively, were at home (p = 0.002). After 6 weeks 36.3% of the patients from the stroke unit and 50.0% from the general medical wards were in an institution (p = 0.02); after 52 weeks 12.7% and 22.7%, respectively, were institutionalized (p = 0.016). After 6 weeks mortality was 7.3% for the stroke unit group and 17.3% for the general medical wards group (p = 0.027). After 52 weeks mortality was 24.6% for the stroke unit group and 32.7% for the general medical wards group (difference not significant). Functional state was significantly better for patients treated in the stroke unit after both 6 and 52 weeks. We conclude that care of patients with acute stroke in a stroke unit improves clinical outcome compared with treatment in general medical wards.
LY178002 reduces rat brain damage after transient global forebrain ischemia.
Authors: Clemens J A , Ho P P , Panetta J A
Published: June 2011

Several feasible mechanisms have been proposed as sources of neuronal damage from ischemia and subsequent reperfusion. Included among these are oxidative damage caused by free radical production and lipid peroxidation and products derived from phospholipid breakdown. A series of 4-thiazolidinone compounds represented by LY178002 (5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene-4-thiazolidinon e) have been described as inhibitors of multiple enzymes in the arachidonic acid cascade, including fatty acid cyclooxygenase, 5-lipoxygenase, and phospholipase A2. Accordingly, we evaluated LY178002 in a four-vessel occlusion model of global forebrain ischemia with reperfusion. A 2-hour pretreatment of 11 male Wistar rats with 150 mg/kg LY178002 significantly protected against striatal (p = 0.0007) and hippocampal CA1 (p = 0.006) damage after 30 minutes of global ischemia. Similar protection was observed for the striatum (p = 0.005) and hippocampal CA1 layer (p = 0.025) after pretreatment of 13 rats with 50 mg/kg LY178002. We further evaluated LY178002 as a possible inhibitor of lipid peroxidation because part of its chemical structure incorporates the aromatic backbone of the known antioxidant butylated hydroxytoluene. We found LY178002 to be a potent inhibitor of iron-dependent lipid peroxidation. Few substances possessing a single pharmacological activity have been found to be of significant therapeutic benefit in global ischemia of 30 minutes' duration because the mechanisms that lead to cell death in response to ischemia are likely to be multifactorial. Thus, the efficacy of LY178002 in this model may be due to its ability to inhibit multiple sources of damage.
Stroke from other etiologies masquerading as migraine-stroke.
Authors: Shuaib A
Published: June 2011

There has been a recent increase in the number of studies dealing with migraine-stroke. I describe five patients in whom migraine-stroke was the clinical diagnosis but in whom the subsequent clinical events or autopsy showed a different mechanism for the cerebral infarction. Three patients had arterial dissection (one proven at autopsy), one had marantic endocarditis that had been missed on two echocardiograms (proven at autopsy), and one had generalized atherosclerosis and diabetes. These patients demonstrate that important and different etiologies may produce what seems to be the migraine-stroke syndrome. The result may be failure to recognize specific therapeutic measures that could have vitally important benefit to the patient.
Review of the variability of the territories of the major cerebral arteries.
Authors: van der Zwan A , Hillen B
Published: June 2011

The results of recent model studies indicate that the variability in territorial distribution of the major cerebral arteries may be much greater than has been previously recognized. We review the literature on the cortical and intracerebral territories of the anterior, middle, and posterior cerebral arteries. Although most authors claim that these territories are relatively consistent, the results of their studies show many and considerable discrepancies. The variability described by Beevor has been neither excluded nor completely confirmed, yet somehow the concept of a relatively unchanging pattern of the peripheral cerebral vascularization has gradually settled into the literature. We discuss the considerable variability of the cerebral territories, as well as the discrepancies in investigation techniques, injection materials, and specimen conditions that could be factors producing these dissimilar results. Our study shows that there are no arguments in the literature to negate the variability of the cerebral territories.
Clinical and hemodynamic aspects of low-flow infarcts.
Authors: Weiller C , Ringelstein E B , Reiche W , Buell U
Published: June 2011

We used single-photon emission computed tomography to measure cerebral blood flow, cerebral blood volume, and cerebral perfusion reserve and transcranial Doppler sonography with CO2 stimulation to assess hemispheric vasomotor reactivity in 37 patients and in normal controls. Computed tomography and magnetic resonance imaging were performed to differentiate morphologically low-flow infarcts (n = 17) from territorial infarcts (n = 20). In patients with either type of infarct, blood flow was decreased and blood volume was increased in the infarcted areas compared with the same areas in the controls. Perfusion reserve and vasomotor reactivity were significantly reduced in patients with territorial infarcts and carotid artery occlusions (n = 12) and even more reduced in patients with low-flow infarcts (p less than 0.001). Both parameters were normal in patients with cardiac embolic territorial infarcts (n = 8). In patients with territorial infarcts, blood flow and perfusion reserve changes were restricted to the infarcted areas, whereas in patients with low-flow infarcts, regions of decreased perfusion reserve considerably exceeded the area of the infarct. Low-flow infarcts are related to the hemodynamic effects of severe extracranial carotid artery disease.
A pilot study of hyperbaric oxygen in the treatment of human stroke.
Authors: Anderson D C , Bottini A G , Jagiella W M , Westphal B , Ford S , Rockswold G L , Loewenson R B
Published: June 2011

We administered hyperbaric oxygen or air in a double-blind prospective protocol to 39 patients with ischemic cerebral infarction. We interrupted the study when we noticed what appeared to be a trend favoring the air-treated patients, whose neurological deficits were less severe (mean +/- SEM score on graded neurological examination: air, 25.6 +/- 4.9; oxygen, 34.5 +/- 7.5) and whose infarcts were smaller (air, 29.0 +/- 12.2 cm3; oxygen, 49.2 +/- 11.7 cm3) at 4 months. The trend, we decided, was probably an artifact of the randomization process. Nevertheless, we chose not to resume the trial because the treatment was difficult to administer by schedule (for various reasons the treatment protocol was broken in 15 of the 39 patients), was poorly tolerated (eight of the 39 patients refused to continue treatments), and did not produce dramatic improvement.
Ischemic cerebrovascular complications and risk factors in idiopathic hypertrophic subaortic stenosis.
Authors: Russell J W , Biller J , Hajduczok Z D , Jones M P , Kerber R E , Adams H P
Published: June 2011

To determine the risk and time to cerebrovascular complications with idiopathic hypertrophic subaortic stenosis, we studied 119 patients (66 men and 53 women) with evidence of this disease based on strict echocardiographic criteria and followed them up for a mean +/- SEM of 6.5 +/- 0.6 years. Cerebral ischemic events occurred in 26 patients (22%), and in five patients stroke was the initial presenting event. Men had cardiac symptoms at a younger age than women, but there was no significant difference in age at the time of stroke. Cardioembolic cerebrovascular events were associated with atrial fibrillation and left atrial enlargement, whereas atheroembolic events were associated with hypertension. An increased risk of stroke was associated with female sex, mitral anulus calcification, hypertension, and atrioventricular conduction delay. Unlike most previous series, this study shows that patients with idiopathic hypertrophic subaortic stenosis may present with stroke.
Hypertension with hemodilution prevents multifocal cerebral hypoperfusion after cardiac arrest in dogs.
Authors: Leonov Y , Sterz F , Safar P , Johnson D W , Tisherman S A , Oku K
Published: June 2011

Improved neurological outcome with postarrest hypertensive hemodilution in an earlier study could be the result of more homogeneous cerebral perfusion and improved O2 delivery. We explored global, regional, and local cerebral blood flow by stable xenon-enhanced computed tomography and global cerebral metabolism in our dog cardiac arrest model.

Ventricular fibrillation cardiac arrest of 12.5 minutes was reversed by brief cardiopulmonary bypass, followed by life support to 4 hours postarrest. We compared control group I (n = 5; mean arterial blood pressure, 100 mm Hg; hematocrit, greater than or equal to 35%) with immediately postarrest reflow-promoted group II (n = 5; mean arterial blood pressure, 140-110 mm Hg; hypervolemic hemodilution with plasma substitute to hematocrit, 20-25%).

After initial hyperemia in both groups, during the "delayed hypoperfusion phase" at 1-4 hours postarrest, global cerebral blood flow was 51-60% of baseline in group I versus 85-100% of baseline in group II (p less than 0.01). Percentages of brain tissue voxels with no flow, trickle flow, or low flow were lower (p less than 0.01) and mean regional cerebral blood flow values were higher in group II (p less than 0.01). Global cerebral oxygen uptake recovered to near baseline values at 3-4 hours postarrest in both groups. Postarrest arterial O2 content, however, in hemodiluted group II was 40-50% of that in group I. Thus, the O2 uptake/delivery ratio was increased (worsened) in both groups at 2-4 hours postarrest.

After prolonged cardiac arrest, immediately induced moderate hypertensive hemodilution to hematocrit 20-25% can normalize cerebral blood flow patterns (improve homogeneity of cerebral perfusion), but does not improve cerebral O2 delivery, since the flow benefit is offset by decreased arterial O2 content. Individualized titration of hematocrit or hemodilution with acellular O2 carrying blood substitute (stroma-free hemoglobin or fluorocarbon solution) would be required to improve O2 uptake/delivery ratio.
Uptake and release of serotonin in rat cerebrovascular nerves after subarachnoid hemorrhage.
Authors: Szabò C , Emilsson K , Hardebo J E , Nystedt S , Owman C
Published: June 2011

Serotonin released from platelets has been suggested as one substance causing the vasospasm following subarachnoid hemorrhage. We studied whether such serotonin is able to constrict pial vessels.

We studied the uptake of serotonin in pial perivascular nerves by immunohistochemistry. We measured the contractile response in rat basilar artery after in vitro incubation with serotonin and during electrical field stimulation of perivascular nerves following experimental subarachnoid hemorrhage.

After incubation with serotonin, electrical field stimulation caused a tetrodotoxin- and ketanserin-blockable contractile response. We observed no such response in vessels from rats treated with 6-hydroxydopamine or after blockade of serotonin uptake. After subarachnoid hemorrhage, a pronounced network of serotonin-immunoreactive nerve fibers was demonstrated in the vessel wall. In vessels from control rats, no serotonin fibers were seen, and in vessels from 6-hydroxydopamine-treated animals with subarachnoid hemorrhage only a few such fibers were seen. Electrical field stimulation of the basilar artery from rats tested 2 or 16 hours (but not 10 minutes or 24 hours) after subarachnoid hemorrhage showed contractile responses that were prevented by tetrodotoxin, ketanserin, and prior 6-hydroxydopamine treatment.

Our study demonstrates a capacity of the perivascular sympathetic nerves to take up serotonin both in vitro and during the early phase of subarachnoid hemorrhage. Such uptake may help to remove excess serotonin from the subarachnoid space. Only if serotonin is subsequently released upon nerve activation may minor smooth muscle contraction develop.