bluuebunny/crossref_metadata_2025 huggingface dataset:
Alteration of serum pituitary hormone levels in postmenopausal women with stroke.
Authors: Pepper G M , Koenigsberg R , Zito J L , Deutsch S
Published: June 2011

The aim of this study was to determine if circulating levels of pituitary hormones are altered by stroke and, if so, whether these alterations offer insight into specific neurochemical pathways in the region of the central nervous system injury.

Twenty-eight consecutive postmenopausal women undergoing computed tomographic imaging of the brain for evaluation of clinical evidence of stroke underwent blood sampling for determination of serum levels of luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, triiodothyronine, prolactin, estradiol, and sex hormone--binding globulin.

In stroke involving the caudate, serum levels of luteinizing hormone and follicle-stimulating hormone were reduced to 16% and 24% of concentrations found in those with stroke outside of the basal ganglia (p < 0.03 and p < 0.01, respectively). Levels of estradiol, sex hormone-binding globulin, thyroid-stimulating hormone, and prolactin were similar in all stroke groups. Nonspecific biochemical effects of stress that might influence hormone concentrations were assessed by measurement of serum triiodothyronine, the level of which is a sensitive biochemical correlate of disease severity. These levels were not different between stroke groups.

Stroke involving the caudate nucleus may interrupt neurotransmitter pathways involved in control of secretion of gonadotropins. Peripheral levels of these hormones may serve as a marker for central neurochemical disturbances associated with stroke in specific brain regions.
Spinal infarction. A follow-up study.
Authors: Pelser H , van Gijn J
Published: June 2011

Ten patients with spinal cord infarction were followed up after 1 to 27 (median, 3) years to establish the sequelae of the disease in the long term.

Eight surviving patients were interviewed about mobility, pain, and activities of daily living. All 8 patients had residual weakness in the legs; 7 of them were able to live at home without professional help. All but 1 suffered from continuous pain, which was not dependent on the degree of weakness.

Motor function had improved to some extent in all patients, but pain is a disabling feature in the long term.
Optimality principles and flow orderliness at the branching points of cerebral arteries.
Authors: Rossitti S , Löfgren J
Published: June 2011

The cerebral arteries present an optimum blood flow/vessel radius relation. However, branch angles may vary widely in the cerebral arteries because the parametric optimization of branch angles is irrelevant in terms of energy cost. The position of the flow divider in extracranial arteries has been suggested to be optimum in flow orderliness. No data exist on the flow divider of cerebral arteries. Thus, we hypothesized that in the cerebral arteries the apex of the bifurcations, which is known to be the site of maximum hemodynamic stress in a vascular network, may normally lie in a non-optimum position relative to the dividing flow streamline in the parent vessel, leading to disturbed laminar flow and increased vessel wall shear stress at the apical region despite the optimum blood flow/vessel radius relation. The objective of this study was to test our hypothesis.

We measured the branch angles and diameters of parent and branch segments of the anterior cerebral artery system from lateral projections to minimize the measurement error on angiographs chosen at random from normal sets. The position of the apex of the bifurcations in relation to the ostium of the parent artery (gamma) and the ratio of the branch diameters (d2/d1) were compared. Optimum curves for these parameters were calculated by a mathematical model. In addition, the separation of flow streamlines according to gamma was calculated for each bifurcation and related to the division of flow required by each branch according to the optimum blood flow/vessel radius relation.

The data points on gamma and d2/d1 and the separation of flow according to gamma and the division of flow required by the branches were found to scatter around the optimum curves. However, a trend toward the theoretical optimum is discernible. The data points are suggested to be a random sample from a normal distribution around the optimum (.40 < P < .50).

The bifurcations of the cerebral arteries appear to be optimized to avoid increased hemodynamic stresses both globally and locally in the same manner as extracranial arteries.
Fulminant brain necrosis from atrial myxoma showers.
Authors: Browne W T , Wijdicks E F , Parisi J E , Viggiano R W
Published: June 2011

Atrial myxoma is uncommon and may be associated with brief isolated ischemic events. We describe a patient with atrial myxoma and an incompletely evaluated ischemic stroke followed 1 year later with almost complete brain necrosis.

A 63-year-old woman presented with a rapidly progressive illness resulting in coma within 24 hours from multiple myxomatous emboli. Cranial computed tomographic scan demonstrated multiple hypodensities in both cerebellar and cerebral hemispheres. Postmortem examination revealed virtually complete brain necrosis, multiple peripheral artery embolizations, embolization in the coronary arteries with acute myocardial infarction, and tumor emboli in the spleen and kidneys.

Although uncommon, atrial myxoma may present as a fatal multiple organ embolization that includes both anterior and posterior circulation territories of the brain.
Posterior ischemia during an attack of transient global amnesia.
Authors: Lin K N , Liu R S , Yeh T P , Wang S J , Liu H C
Published: June 2011

The popular concept that cerebral ischemia causes transient global amnesia has been difficult to prove by cerebral blood flow studies during attacks because the transient global amnesia attacks are so short.

We performed single-photon emission computed tomography (SPECT) of the brain and neuropsychological assessment in a 37-year-old woman during a 10-hour attack and twice thereafter. A neuropsychological evaluation 3 hours after the onset of transient global amnesia revealed severe impairment of recent memory and verbal fluency, both of which returned to normal 2 and 28 days later, respectively. A 99mTc-labeled hexamethylpropyleneamine oxime SPECT of the brain performed 6 hours after the onset showed multiple perfusion defects in both occipital lobes, the medial left temporal lobe, and the left thalamus. A second brain SPECT performed 3 days later showed perfusion defects in only the occipital regions. A third brain SPECT performed 28 days later was normal. The patient's brain computed tomographic scan, electroencephalogram, duplex ultrasound of the carotid artery, and echocardiogram were normal.

The perfusion defects revealed by the brain SPECT during the transient global amnesia attack indicated ischemia in the territory of the posterior cerebral arteries, which partially resolved in 3 days and completely resolved by 28 days.
Increased immunoglobulin binding to cerebral endothelium in patients with antiphospholipid antibodies.
Authors: Hess D C , Sheppard J C , Adams R J
Published: June 2011

There is a strong link between antiphospholipid antibodies and stroke. The mechanism of action of antiphospholipid antibodies is unknown. Most theories of pathogenesis center around platelet or endothelial cell dysfunction. Our aim was to determine if there were immunoglobulins in the sera of patients with antiphospholipid antibodies that bind human brain microvascular endothelial cells.

We studied sera from three groups of subjects: patients with antiphospholipid antibodies and stroke (group 1), healthy control subjects (group 2), and patients with stroke but without antiphospholipid antibodies (group 3). We isolated human brain microvascular endothelial cells from temporal lobectomy specimens and used a cellular enzyme-linked immunosorbent assay (ELISA) to measure immunoglobulin binding to endothelial cells derived from human brain and from human umbilical vein. We used a chromium release assay to measure cytotoxicity.

Patients with antiphospholipid antibodies and stroke had significantly higher immunoglobulin binding to human brain microvascular endothelial cells than subjects in the other groups ([ELISA index+standard deviation], 63 +/- 37 [group 1] versus 7 +/- 7 [group 2] versus 7 +/- 7 [group 3], P < .001). There was, however, poor correlation between binding to brain endothelial cells and binding to cardiolipin. The binding to brain microvascular cells was not specific to brain endothelium, as similar results were found in an ELISA using human umbilical vein cells. There was no evidence of complement-mediated brain endothelial cell cytotoxicity.

Patients with stroke and antiphospholipid antibodies frequently have human brain microvascular endothelial-reactive antibodies in their serum. These antibodies are distinct from those to cardiolipin. We found no evidence that these antibodies are cytotoxic.
Stroke mortality and case-fatality rates in three geographic areas of Finland from 1983 to 1986.
Authors: Sarti C , Tuomilehto J , Sivenius J , Kaarsalo E , Narva E V , Salmi K , Salomaa V , Torppa J
Published: June 2011

Our aim was to describe the mortality and early case-fatality rates of stroke in three geographic areas of Finland during 1983 to 1986 by means of a community-based stroke register and to estimate the accuracy of registration of stroke deaths in the official statistics compared with the FINMONICA stroke register.

Annual and average mortality and case-fatality rates of stroke were derived from data collected in the FINMONICA stroke register during 1983 to 1986. Age-specific and age-standardized rates were calculated for the three areas, and the results were compared with the official mortality statistics and with the case-fatality figures published previously in the literature for Finland and elsewhere.

Mortality from stroke in the three FINMONICA areas was between 73 and 90 per 100,000 per year among men aged 25 to 74 years and between 42 and 55 per 100,000 per year among women in the same age group. Average case-fatality was similar in the three areas and globally high: 20% to 27% in men and 24% to 28% in women. Approximately half of the fatal strokes occurred within less than 2 days from the onset of the attack, and a further 25% within the first week. Hemorrhagic strokes accounted for 54% to 81% of all fatal strokes occurring in less than 2 days among men, while among women the corresponding proportions varied in the three areas between 35% and 74%. Of cerebral infarctions, approximately 28% to 37% among men and 19% to 20% among women were fatal within less than 2 days. Although the number of fatal strokes was similar in both the FINMONICA register and official mortality statistics, only 82% to 85% of the stroke cases were common in both registers; a further 13% to 14% of the cases classified as stroke deaths in the FINMONICA register could also be found in the official mortality statistics, but the underlying cause of death was something other than stroke.

The reliability of the Finnish official mortality statistics with regard to stroke deaths is reasonably good in aggregate numbers, but at the individual level considerable discrepancies seem to occur. Mortality from stroke in Finland has not declined further after 1979 and remains high internationally. Early case-fatality of stroke also seems higher in Finland than in most other countries. We believe that both the high incidence of stroke and the severity of the attacks are contributing to mortality and case-fatality rates of stroke in Finland.
Bilirubin levels in subarachnoid clot and effects on canine arterial smooth muscle cells.
Authors: Trost G R , Nagatani K , Goknur A B , Haworth R A , Odell G B , Duff T A
Published: June 2011

Previous studies have suggested that bilirubin is a potential contributor to cerebral vasospasm. The purpose of this investigation was to determine whether bilirubin accrues in subarachnoid clot, whether its vasoconstrictive effect could involve a direct action on arterial smooth muscle cells, and, if so, whether bilirubin affects their Ca2+ uptake.

Subarachnoid clots were analyzed for bilirubin using high-performance liquid chromatography. The length and 45Ca2+ uptake of vascular smooth muscle cells enzymatically dissociated from canine carotid arteries were measured before and after exposure to bilirubin solution. Additional experiments were conducted on cultured smooth muscle cells from canine basilar artery and on ATP-depleted cardiac myocytes.

Mean +/- SE bilirubin concentration in experimental clot was 263 +/- 35.7 mumol/L. Vascular smooth muscle cells exposed to bilirubin showed progressive shortening (P < .01) and an increased uptake of 45Ca2+ (P < .001). Contraction was prevented by Ca(2+)-free media but not by verapamil. Experiments with heart myocytes showed that bilirubin caused an increased uptake of 45Ca2+ but not of [14C]sucrose.

The results indicate that bilirubin accrues in subarachnoid clot, that it exerts a direct constrictive effect on arterial smooth muscle cells, and that this effect is associated with an increased uptake of Ca2+. Studies on heart myocytes suggest that the Ca2+ uptake induced by bilirubin could be due to a selective increase in membrane permeability to Ca2+.
Morphometry of structural preservation of tunica media in aged and hypertensive human intracerebral arteries.
Authors: Masawa N , Yoshida Y , Yamada T , Joshita T , Sato S , Mihara B
Published: June 2011

Medial smooth muscle cell necrosis has been reported as a lesion that may precede angionecrosis, which is a major cause of not only hypertensive brain hemorrhage but also lacunar infarct. We morphometrically studied a loss of smooth muscle cells in the media of cerebral arteries in relation to clinical risk factors.

The lateral striate, ie, perforating arteries and the medullary arteries in the subcortical white matter of the temporal lobe (100 to 400 microns in diameter) were histologically investigated in 121 autopsied brains. Medial area was measured quantitatively, and the number of nuclei of smooth muscle cells in the area was calculated in 1210 cross-sectional arteries of histological sections. The influence on the structural (ie, smooth muscle cell) preservation of the tunica media (ratio of number of smooth muscle cell nuclei to medial area [N-MA ratio]) of age, blood pressure, serum lipids, and presence of absence of extracerebral severe atherosclerosis was investigated.

The N-MA ratio decreased slightly with age in both arteries. A reverse correlation between N-MA ratio and age was seen in groups both with and without hypertension. The mean N-MA ratio in the hypertensive group was significantly lower than that of the nonhypertensive group (P < .001) in all decades of life. The mean N-MA ratio of the perforating arteries was slightly lower than that of the medullary arteries in both groups. Severe atherosclerosis of the internal carotid arteries, even with hypertension, mitigated a decrease of the N-MA ratio, which was as slight as that in the nonhypertensive group. Serum cholesterol in this group was higher than in both the conventional hypertensive group (P < .005) and the nonhypertensive group (P < .001).

Although both hypertension and age were significant risk factors for medial smooth muscle cell necrosis, hypertension was relatively more significant. Medial smooth muscle cells of the perforating arteries in the basal ganglia were more vulnerable than those of the medullary arteries. Cerebral small arteries in subjects with severe atherosclerosis of the carotid and major cerebral arteries (hypertension in eight of nine subjects) may have been protected from extensive loss of medial smooth muscles presumably because of both high serum cholesterol and decreased wall tensile stress associated with reduced blood perfusion due to severe atherosclerotic stenosis.
Cerebral blood flow in frontal lesions of aneurysms of the anterior communicating artery.
Authors: Rousseaux M , Huglo D , Steinling M
Published: June 2011

The aim of this study was to investigate local and remote regional cerebral blood flow in patients with prefrontal lesions resulting from rupture (and operation) of aneurysms of the anterior communicating artery.

The localization and severity of the lesions were evaluated by magnetic resonance imaging on T2 sequences. Blood flow measurements were performed in 21 patients at least 3 weeks after surgery using single-photon emission computed tomography. Flow values were calculated in 10 regions of interest in each cerebral hemisphere and compared with those of 21 control subjects matched for age.

A drop in regional cerebral blood flow, predominating on the right side, was observed in the frontal areas. Flow values were not reduced in the thalamus and striatum but were significantly elevated in the posterior cortical areas and cerebellum. This latter phenomenon was significantly correlated with the severity of frontal lesions on magnetic resonance imaging.

Blood flow drop in frontal areas was correlated with the cerebral lesions, which predominated in the anterior prefrontal lobe, on the side of the surgical flap; most of these prefrontal lesions were likely due to the surgical procedure and not to classic arterial spasm. Elevated perfusion in the temporo-parieto-occipital cortex and cerebellum might be due to the release of a physiological inhibition exerted by the prefrontal cortex.
Effect of moderate hypothermia on lipid peroxidation in canine brain tissue after cardiac arrest and resuscitation.
Authors: Lei B , Tan X , Cai H , Xu Q , Guo Q
Published: June 2011

We sought to examine the effect of moderate hypothermia (30 degrees C to 32 degrees C) initiated after resuscitation on the scavenging systems of free radicals and lipid peroxidation in canine brain tissue after cardiac arrest and resuscitation.

Twenty-one dogs were divided into four groups: group A, nonischemic controls (shams) (n = 4); group B, 15-minute cardiac arrest without reperfusion (n = 4); group C, 15-minute cardiac arrest and standard resuscitation (n = 6); and group D, 15-minute cardiac arrest and hypothermic resuscitation (n = 7). During the period of 10 to 120 minutes after resuscitation, brain temperature and core temperature in group D remained at 30 degrees C to 32 degrees C and were 4 degrees C to 5 degrees C lower than in group C. For each dog, a sample of right parietal cerebral cortex was obtained from group A, group B, or from group C and group D at 2 hours after resuscitation. The sample was assayed for tissue malondialdehyde (MDA), the content of reduced glutathione (GSH), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX).

In group B, a 15-minute cardiac arrest induced an increase in MDA, a significant reduction of GSH, and no change in SOD and GSH-PX activities compared with group A. In group C, there were further increases in MDA and reductions in GSH content and GSH-PX activity compared with group A; SOD activity remained substantially unchanged. The content of MDA was higher in group D than in group A but less elevated in group D than in group C. The GSH content and SOD and GSH-PX activities were significantly higher in group D than in group C.

Moderate hypothermia initiated after resuscitation can significantly inhibit the accumulation of lipid peroxidation products and the consumption of free radical scavengers in the brain tissue.
Influence of pH on calcium influx during hypoxia in rat cortical brain slices.
Authors: O'Donnell B R , Bickler P E
Published: June 2011

Acidity of brain intracellular and extracellular fluids appears to increase brain injury from stroke, but low extracellular pH decreases the activity of N-methyl-D-aspartate receptor ion channels and decreases calcium influx into isolated neurons. To further investigate the role of acid-base balance in hypoxic brain injury, we studied the influences of intracellular and extracellular pH on calcium influx in cortical brain slices during hypoxia.

Intracellular calcium ([Ca2+]i) and pH (pHi) were measured fluorometrically with the dyes fura-2 and biscarboxyethyl carboxyfluorescein, respectively, during two types of hypoxia: (1) slice perfusate equilibrated with N2/CO2 at pH 6.6 or 6.2 ("gaseous hypoxia") or (2) perfusate equilibrated with 95% O2/5% CO2 plus 100 mumol/L NaCN at pH 7.3, 6.6, or 6.2 ("chemical hypoxia").

Changes in perfusate pH under aerobic conditions did not change [Ca2+]i. However, influx of calcium caused by gaseous or chemical hypoxia increased significantly with decreasing perfusate pH. During chemical hypoxia, the elevation in [Ca2+]i at perfusate pH 6.2 was twice that at perfusate pH 7.3. Change in [Ca2+]i was correlated with perfusate pH but not pHi.

These results, which differ from previous studies showing acid inhibition of calcium influx in isolated neurons, suggest that low extracellular pH may exacerbate cellular injury during severe hypoxia or ischemia in the intact brain.
Basilar artery occlusion in a young patient with Wegener's granulomatosis.
Authors: Savitz J M , Young M A , Ratan R R
Published: June 2011

Stroke is an uncommon sequela of Wegener's granulomatosis, resulting primarily from vasculitic infiltration of small to medium-sized vessels. We describe a young patient with Wegener's granulomatosis and basilar artery occlusion.

A 26-year-old man with histopathologically confirmed Wegener's granulomatosis suffered a brain stem stroke 24 hours after open lung biopsy. Angiography revealed midbasilar artery occlusion.

Patients with Wegener's granulomatosis may experience premature large cerebral vessel occlusion. Putative etiologies in our patient include vasculitis, postoperative hypercoagulability, and/or intraoperative neck positioning leading to embolization.
Initial experience with intravascular ultrasound imaging during carotid endarterectomy.
Authors: Karnik R , Ammerer H P , Winkler W B , Valentin A , Slany J
Published: June 2011

To assess the feasibility of intravascular ultrasound imaging during carotid endarterectomy.

Intravascular ultrasound imaging was performed during carotid endarterectomy in eight patients using an over-the-wire catheter system with a 30-MHz ultrasound probe. In vitro studies were carried out before the intraoperative application, paying special attention to visualization of the wall layers of normal carotid arteries, structures of more or less diseased vessels, and surgically placed materials such as patch, suture material, and fibrin glue. Although intravascular ultrasound failed to distinguish between intima and media in areas of normal intima, fibrotic and calcified plaques were detected clearly. Dacron patch as well as sutures were identified as highly reflective structures.

In seven of the eight patients studied, intravascular ultrasound yielded cross-sectional images of good quality allowing identification of the vessel layers and the structures at the endarterectomy site. In all patients the three layers of the vessel wall were clearly differentiated and the transition zone between the site of endarterectomy and the genuine vessel appeared smooth without intimal flaps or residual arteriosclerotic plaques. In one patient severe eccentric thickening of the media was detected in the distal internal carotid artery. Neither damage of the vessel layers by the shunt nor thrombus formation in the operating area and the internal carotid artery were detected.

Intravascular ultrasound lends itself as a potentially valuable method of quality control during carotid endarterectomy. The method seems to enable an accurate evaluation of the endarterectomy site and the search for residual plaques.
Denial of eye closure in acute stroke.
Authors: Ellis S J , Small M
Published: June 2011

Many patients suffering from stroke exhibit denial of illness. As part of this symptom complex we observed denial of eye closure. We therefore aimed to document the frequency and phenomenology of denial of eye closure in acute stroke.

Denial of eye closure was sought in 43 cases of denial of illness from a series of 400 acute strokes. Subjects underwent a neurological examination, and audiotaped interviews were performed during which they were asked to finger count through their closed eyes and their denial was challenged.

Five of 43 patients with denial of hemiplegia after acute stroke were also found to have denial of eye closure (12%). Denial of eye closure was associated with drowsiness and in all but one patient with disorientation. In the three cases with imaging or autopsy data available, lesions were moderate to large, in the right hemisphere, and involved the frontal lobe. Three subjects confabulated as to what they saw through their closed eyes. One subject mislocalized the hospital closer to her home.

Denial of eye closure occurs in a minority of patients with denial of illness after acute stroke. This phenomenon sheds light on denial as a whole and cannot easily be accounted for by unilateral explanations, such as inattention to one half of the body or loss of sensory input. There are aspects of denial, such as denial of eye closure, mislocalization, and the delusional intensity of beliefs, that can only be understood in cognitive terms.
Tactile extinction and functional status after stroke. A preliminary investigation.
Authors: Rose L , Bakal D A , Fung T S , Farn P , Weaver L E
Published: June 2011

Research has identified a number of factors associated with poststroke recovery, but the prediction of long-term functional outcome remains an uncertain endeavor. In previous work, extinction to tactile, double-simultaneous stimulation has been shown to have short-term predictive utility. The present study was designed to examine its long-term prognostic value and to determine the relative importance of tactile extinction, cognitive functioning, and visual neglect as predictors of poststroke functional status.

Successive admissions to an acute-care facility (n = 26) were assessed three times: 1 month, 3.5 months, and 6 months after stroke. Hierarchical multiple regression, a procedure that maximizes the effect of the variables first entered, was used to predict functional status. Cognitive functioning and visual neglect were forced into the equation on the first step; tactile extinction was entered on the second step. Multivariate analysis of variance was used to compare the functional status of subjects with no extinction versus those who demonstrated extinction at the first assessment and later improved and those who continued to manifest the deficit.

Tactile extinction on the left-hand side of the body was the most important predictor of functional outcome. A significant group-by-time interaction implied that the course of improvement in functional status differed between the groups.

Tactile extinction shows promise as a predictor of poststroke functional status, but further work is required to substantiate the present findings.
Effect of graded hypothermia (27 degrees to 34 degrees C) on behavioral function, histopathology, and spinal blood flow after spinal ischemia in rat.
Authors: Marsala M , Vanicky I , Yaksh T L
Published: June 2011

We used a rat model of reversible spinal ischemia to assess the effect of spinal cord temperature on the development of neurological and histopathologic changes after 20 minutes of reversible aortic occlusion. Spinal cord blood flow and CO2 reactivity was tested by using laser Doppler before and 60 minutes after ischemia.

In halothane (1%)-anesthetized rats, the spinal cord temperature as assessed by using thermocouple in the paraspinal muscles was lowered to 34 degrees, 31 degrees, or 27 degrees C. After ischemia, spinal cord temperature was raised to 37 degrees C for the next 30 minutes. Animals were maintained in this normothermic condition for 8 hours, after which motor and sensory function were assessed. All animals were then anesthetized and perfused with 10% formalin for light microscopic analysis of spinal cords.

In normothermic animals, 20 minutes of ischemia resulted in a loss of CO2 reactivity and hind limb paraplegia with an attendant allodynia that persisted for the 8 hours of reperfusion. Even mild (34 degrees C) hypothermia resulted in significant improvement of neurological function compared with the normothermic group. In paraplegic animals, lumbosacral interneuronal pools localized primarily in laminae III through VII displayed heavy argyrophilic neurons and areas of localized necrosis. In moderate and deep hypothermic animals preservation of CO2 responsivity and complete recovery of neurological function were seen with no detectable histopathologic changes.

These results show that a slight decrease in spinal cord temperature in the peri-ischemic period provides significant protection as measured by histopathology and neurological function.
A long-half-life and fibrin-specific form of tissue plasminogen activator in rabbit models of embolic stroke and peripheral bleeding.
Authors: Thomas G R , Thibodeaux H , Errett C J , Badillo J M , Keyt B A , Refino C J , Zivin J A , Bennett W F
Published: June 2011

We compared the activity of a new long-half-life, fibrin-specific tissue-type plasminogen activator (TPA) variant with that of wild-type TPA in rabbit models of embolic stroke and peripheral bleeding.

In the embolic stroke model. TPA-induced clot lysis is followed by continuous monitoring of a radiolabeled clot lodged in the middle cerebral artery. Twenty-four hours after embolization and treatment with either thrombolytic agent or excipient, the brains are removed, fixed, and evaluated for cerebral hemorrhage. In a parallel template bleeding time experiment, the effects of equipotent doses of the two TPA molecules were measured.

Infusion of wild-type TPA or bolus administration of the TPA variant resulted in dose-dependent clot lysis. The TPA variant was found to be an order of magnitude more potent than wild-type TPA on a milligram-per-kilogram basis. Unlike wild-type TPA, the variant caused less systemic activation of plasminogen (P < .05) and fewer hemorrhagic transformations in this model (P < .05). The TPA variant did not extend template bleeding times.

These findings show that by combining increased fibrin specificity with decreased plasma clearance, it is possible to produce a thrombolytic agent that is more convenient and more potent than wild-tpe TPA. At the same time the significant reduction in hemorrhagic conversions may be attributable to the conservation of systemic plasminogen seen with this molecule.
Modification of platelet aggregation by leukocytes in acute ischemic stroke.
Authors: Grau A J , Sigmund R , Hacke W
Published: June 2011

Platelet aggregation plays an important role in the pathogenesis of thromboembolic cerebrovascular disease. Leukocytes can efficiently stimulate as well as inhibit platelet aggregability. We studied the influence of leukocytes on collagen-induced platelet aggregation in patients with acute ischemic stroke.

We investigated 23 patients within 2 days after stroke and 23 healthy age- and sex-matched control subjects and determined collagen-induced platelet aggregation in platelet-rich plasma with or without addition of polymorphonuclear or mononuclear leukocytes.

Platelet aggregation without leukocytes tended to be lower in patients than in control subjects (P = .06). Mononuclear leukocytes reduced (P = .018) and polymorphonuclear leukocytes tended to reduce (P = .06) platelet aggregation in patients. Leukocytes did not significantly alter platelet aggregation in control subjects. In the presence of either mononuclear or polymorphonuclear leukocytes, platelet aggregation was significantly lower in patients than in control subjects (P = .004 and P = .008). The ratio of polymorphonuclear leukocytes to platelets in venous blood was higher in patients than in control subjects (P < .001).

Mononuclear--and less clearly polymorphonuclear-leukocytes possess a platelet aggregation-inhibiting potential in the early stages after ischemic stroke, a feature with possible antithrombotic effects.
Alterations in plasma concentrations of natriuretic peptides and antidiuretic hormone after subarachnoid hemorrhage.
Authors: Isotani E , Suzuki R , Tomita K , Hokari M , Monma S , Marumo F , Hirakawa K
Published: June 2011

Hyponatremia is a common complication after subarachnoid hemorrhage. In this study we investigated the relations among hyponatremia, plasma natriuretic peptides, and antidiuretic hormone concentrations after subarachnoid hemorrhage.

Blood samples for radioimmunoassay measurement of plasma brain natriuretic peptide-like immunoreactivity, atrial natriuretic peptide-like immunoreactivity, and antidiuretic hormone were obtained every 2 to 4 days until day 14 after subarachnoid hemorrhage.

Eleven of 20 patients with verified subarachnoid hemorrhage demonstrated mild hyponatremia (126 mEq/L < serum sodium < 135 mEq/L) during their clinical course. Atrial natriuretic peptide and antidiuretic hormone concentrations were significantly elevated on days 0 to 2 after onset of subarachnoid hemorrhage. Atrial natriuretic peptide concentrations remained high in patients who developed mild hyponatremia on days 6 to 14 after onset of subarachnoid hemorrhage. In contrast, antidiuretic hormone concentrations became significantly lower during the second week in these patients.

Mild hyponatremia after subarachnoid hemorrhage may be attributable not to the syndrome of inappropriate secretion of antidiuretic hormone but to cerebral salt-wasting syndrome. Atrial natriuretic peptide may be a causal natriuretic factor in cerebral salt-wasting syndrome.
Leukocyte-induced acute endothelial dysfunction in middle cerebral artery in rabbits. Response to aggregating platelets.
Authors: Akopov S E , Sercombe R , Seylaz J
Published: June 2011

Recent evidence suggests a possible role for leukocytes in angiospastic reactions of large cerebral arteries. This study examined the effect of activation of endogenous circulating leukocytes on endothelium-dependent relaxation in the middle cerebral artery in rabbits.

Leukocytes were activated by rapid injection of either 40 micrograms/kg phorbol 12-myristate 13-acetate, or 0.2 mg/kg N-formyl-methionyl-leucylphenylalanine into the left carotid artery. Control rabbits received an equal volume of vehicle. Concentration-dependent isometric tension responses of the left and right middle cerebral artery to the dilators acetylcholine, ADP, sodium nitroprusside, or calcium ionophore (A23187), as well as to aggregating platelets, were compared in vitro in control animals and in animals killed 10 minutes after the injection of leukocyte activators in normal and leukocyte-depleted rabbits.

In the control animals there was no significant difference in the reactivity of the left and right middle cerebral arteries. The injection of the leukocyte activators led to enhanced contractile responses to aggregating platelets and a significant reduction in the endothelium-dependent relaxation in response to acetylcholine, ADP, and A23187 in the left middle cerebral artery (the injected side), whereas the effect of an endothelium-independent dilator sodium nitroprusside remained unchanged. In leukocyte-depleted rabbits the injection of either of the leukocyte activators used did not induce significant changes in the reactivity of the left middle cerebral artery.

Intravascular leukocyte activation appears to induce an acute disturbance of the endothelium-dependent relaxation. Under these conditions, platelet activation might result in marked angiospastic reactions of large cerebral arteries.
Calpain inhibitor AK295 protects neurons from focal brain ischemia. Effects of postocclusion intra-arterial administration.
Authors: Bartus R T , Hayward N J , Elliott P J , Sawyer S D , Baker K L , Dean R L , Akiyama A , Straub J A , Harbeson S L , Li Z
Published: June 2011

This research was performed to determine whether a selective inhibitor of the calcium-dependent protease, calpain, could reduce ischemia-associated brain damage when peripherally administered after a vascular occlusion.

A variation of the rat middle cerebral artery occlusion model was used. A range of doses of AK295 (a novel calpain inhibitor synthesized for this purpose) was continuously infused through the internal carotid artery, beginning 1.25 hours from the initiation of the occlusion. Rats were killed at 21 hours, and the infarct volume was quantified.

Postocclusion (1.25-hour) infusion of the calpain inhibitor AK295 elicited a dose-dependent neuroprotective effect after focal ischemia. The highest dose tested (3 mg/kg per hour) afforded the maximum effect, illustrated by a 32% reduction in infarct volume 21 hours after the ischemia (vehicle, 81.7 +/- 4.7 mm3; AK295, 54.9 +/- 6.9 mm3; P < .007).

These data provide the first evidence that a peripherally administered calpain inhibitor can protect against ischemic brain damage. They offer further support for an important role of calpain proteolysis in the brain degeneration associated with cerebral ischemic events and suggest that selective calpain inhibitors provide a rational, novel, and viable means of treating such neurodegenerative problems.
Very early demonstration of secondary pyramidal tract degeneration by computed tomography.
Authors: Kazui S , Kuriyama Y , Sawada T , Imakita S
Published: June 2011

While magnetic resonance imaging has revealed progressive changes in the pyramidal tract in accordance with histopathologic stages of wallerian degeneration secondary to a supratentorial lesion, computed tomography (CT) has only demonstrated a shrinkage of the pyramidal tract in the midbrain or pons during the chronic stage. We present a patient with frontoparietal subcortical hemorrhage in whom serial CT scans clearly demonstrated wallerian degeneration along the axis of the pyramidal tract early in the acute stage.

A 63-year-old man with a history of hypertension suddenly developed a deterioration of consciousness, transcortical mixed aphasia, and dense hemiplegia on the right side. CT scans revealed a massive intracerebral hematoma in the frontoparietal subcortices of the left hemisphere. Although initial CT did not detect any hypodense areas along the left pyramidal tract below the hematoma, ill-defined areas of decreased density appeared in the posterior limb of the internal capsule, cerebral peduncle of the midbrain, and pontine base of the left side on day 13 after the stroke. These areas became well demarcated on day 22 and persisted thereafter.

An extensive hematoma can interrupt the pyramidal tract fibers that arise not only from the motor cortex and caudal premotor cortex but also from the somatosensory and parietal cortices, allowing very early CT demonstration of wallerian degeneration of the pyramidal tract.
Cerebral emboli detected during bypass surgery are associated with clamp removal.
Authors: Barbut D , Hinton R B , Szatrowski T P , Hartman G S , Bruefach M , Williams-Russo P , Charlson M E , Gold J P
Published: June 2011

Transcranial Doppler ultrasonography detects embolic signals during coronary artery bypass surgery. The relationship between embolization and specific events of bypass surgery is unclear.

With this technique, 20 patients undergoing bypass surgery were continuously monitored from inception to discontinuation of bypass.

Embolic signals were detected in all patients. Of all embolic signals, 34% were detected as aortic cross-clamps were removed, and another 24% as aortic partial occlusion clamps were removed. Only 5% were detected at inception of bypass. Rates for embolization were 15.15 embolic signals per minute at cross-clamp removal, 10.9 embolic signals per minute at partial occlusion clamp removal, and fewer than 3 embolic signals per minute at other times. Correlation was found between the number of emboli, severity of aortic atheromatosis, and neurocognitive deterioration.

The majority of emboli detected during coronary artery bypass grafting are associated with the release of clamps. Clamp manipulation may lead to release of aortic atheromatous debris. These emboli may be relevant to neurocognitive outcome.
Neuroprotective effects of tetrodotoxin as a Na+ channel modulator and glutamate release inhibitor in cultured rat cerebellar neurons and in gerbil global brain ischemia.
Authors: Lysko P G , Webb C L , Yue T L , Gu J L , Feuerstein G
Published: June 2011

Studies examining the role of tetrodotoxin-sensitive ion channels in hypoxic-ischemic neuronal damage have concluded that sodium influx is an important initiating event. We examined the neuroprotectant effect of tetrodotoxin on both cultured cerebellar neurons and on CA1 hippocampal neurons of gerbils exposed to brain ischemia.

We studied neuroprotective mechanisms using cultured rat cerebellar granule cells exposed to veratridine, which induced cytotoxicity, neurotransmitter release, and calcium influx. Survival of gerbil CA1 neurons was examined by direct neuron counts 7 days after 6 minutes of global ischemia with reperfusion.

Tetrodotoxin protected cultured neurons in a dose-dependent manner from veratridine-induced toxicity (protective concentration [PC50] = 22 nmol/L). Veratridine induced [3H]aspartate efflux that was sodium dependent, only 25% calcium dependent, and was inhibited by tetrodotoxin (inhibitory concentration [IC50] = 60 nmol/L). Veratridine initiated increases in intracellular calcium that were also reversed by tetrodotoxin (IC50 = 63 nmol/L); reversal was dependent on the sodium-calcium exchanger and the sodium-potassium pump. Neuroprotection of 90% (n = 10; P = .001 versus vehicle) of gerbil CA1 hippocampal neurons was achieved by pretreatment with 2 ng of tetrodotoxin delivered three times intracerebroventricularly, without causing hypothermia.

Sodium channel blockers like tetrodotoxin may have utility in treatment of ischemic neuronal injury by preventing excessive neuronal depolarizations, limiting excitotoxic glutamate release through reversal of the sodium-dependent glutamate transporter, preventing intracellular calcium overload, preserving cellular energy stores, and allowing recovery of ionic homeostasis through operation of the sodium-calcium exchanger.
Restricted acral sensory syndrome following minor stroke. Further observation with special reference to differential severity of symptoms among individual digits.
Authors: Kim J S
Published: June 2011

Restricted acral sensory syndrome (RASS) after minor stroke most often manifests as a cheiro-oral syndrome. However, recent studies have described more varied patterns of RASS and also have reported that the degree of sensory symptoms may vary among individual digits. Until recently, however, there have been no reports in which sufficient numbers of patients were studied with detailed information on the symptomatic severity among individual digits.

In this report, I describe 30 patients presenting with RASS secondary to minor stroke. Computed tomographic scan and/or magnetic resonance imaging identified lesions in the lateral thalamus in 11, midbrain in 2, pontine tegmentum in 8, capsulo-corona radiata in 5, and frontoparietal subcortical-cortical areas in 4 patients. The patterns of RASS were cheiro-oral in 10, cheiro-oral-pedal in 8, cheiro-pedal in 4, restricted to palm and/or fingers in 7, and periotal-pedal in 1. Dominant involvement of upper lip, thumb, and index finger was frequent, especially in patients with thalamic and thalamocortical lesions. In patients with cortical-subcortical lesions, cheiro-oral or restricted finger involvements were observed, while the foot was spared. In patients with pontine lesions, bilateral RASS was occasionally observed, and the pattern of preponderant involvement of the first two digits was not apparent.

These patterns of RASS generally agree with the previously observed sensory topography of monkeys, and they support anatomic proximity of sensory fibers from acral parts of the body. However, other mechanisms such as differential vulnerability of generation of paresthesia in different body parts or a low-threshold concept based on disproportionately large representing areas for the acral parts of the body in the human sensory system may also be required to explain some of the clinical observations.
Evaluation of risk of hemorrhagic transformation in local intra-arterial thrombolysis in acute ischemic stroke by initial SPECT.
Authors: Ueda T , Hatakeyama T , Kumon Y , Sakaki S , Uraoka T
Published: June 2011

Thrombolytic therapy was carried out on patients with acute ischemic stroke, and the risk of hemorrhagic transformation was evaluated from the residual cerebral blood flow (CBF) by pretherapeutic single-photon emission-computed tomography (SPECT).

Local intra-arterial thrombolytic therapy was carried out using urokinase or recombinant tissue plasminogen activator (rt-PA) within 6 hours from the onset in 34 patients in whom no hypodensity areas were observed on the initial computed tomography examination. In the 20 patients with carotid territory occlusion who underwent 99mTc-labeled hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT, the residual CBF of the ischemic region was evaluated semiquantitatively by calculating two parameters: the ischemic regional activity to cerebellar activity ratio (R/CE ratio) and asymmetry index (AI).

The occluded vessels could be recanalized in 22 (92%) of the 24 patients in the urokinase group and in all 10 of the patients in the rt-PA group. Hemorrhagic transformation appeared in 4 patients in the urokinase group and 3 patients in the rt-PA group. Among the 20 patients who underwent SPECT before the treatment, the residual CBF was lower in the 5 patients who developed hemorrhagic transformation than in the 15 who did not (P < .05). Hemorrhagic transformation occurred in all patients with R/CE ratio of less than 0.35 and AI of more than 1.5.

The risk of hemorrhagic transformation after recanalization of occluded vessels by local intra-arterial thrombolytic therapy was considered to be high when the pretherapeutic residual CBF was markedly reduced.
Fish consumption and risk of stroke. The Zutphen Study.
Authors: Keli S O , Feskens E J , Kromhout D
Published: June 2011

A low-to-moderate average daily fish consumption has been reported to convey protection against coronary heart disease incidence and mortality. Currently there is no information about its effect on stroke risk.

In 1960, 1965, and 1970 cross-check dietary histories were obtained in 552 men aged 50 to 69 years in 1970 in the town of Zutphen, The Netherlands. The association between fish consumption and stroke incidence in the period 1970 to 1985 was assessed by Cox proportional hazards models. Adjustments were made for confounding by age, systolic blood pressure, cigarette smoking, serum total cholesterol, energy intake, alcohol consumption, and prescribed diet.

The mean fish consumption in 1970 was 17.9 g/d. Men who consumed more than 20 g of fish per day in 1970 had a reduced risk of stroke compared with those who consumed less fish. The hazard ratio (HR) amounted to 0.49 (95% confidence interval [CI], 0.24 to 0.99), and did not change after adjustment for potential confounders. Fewer strokes occurred among the 301 men who always reported fish consumption between 1960 and 1970 than among the men who changed fish consumption habits between 1960 and 1970 or did not consume fish at all (HR, 0.63; 95% CI, 0.34 to 1.16).

These results suggest that consumption of at least one portion of fish per week may be associated with a reduced stroke incidence.