bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcium ionophore and acetylcholine dilate arterioles on the mouse brain by different mechanisms.
Authors: Rosenblum W I , McDonald M , Wormley B
Published: June 2011

Pial arterioles on the surface of the mouse brain were observed in vivo under a chamber with a glass window. When placed under the window, calcium ionophore, acetylcholine, and previously acidified sodium nitrite each dilated the arterioles. If the cyclooxygenase inhibitors indomethacin or acetylsalicylic acid were first placed in the chamber, subsequent dilation of the arterioles by calcium ionophore was reduced to essentially zero. Similar blockade of cyclooxygenase failed to significantly reduce dilation by acetylcholine or sodium nitrite. We have previously shown that dilations by calcium ionophore and acetylcholine were endothelium dependent. Our present experiments show that the endothelium-dependent mechanism for dilation by calcium ionophore is cyclooxygenase dependent, while that for acetylcholine is not. This implies that, in pial arterioles, the endothelium-derived relaxing factor for acetylcholine differs from that for calcium ionophore. This agrees with data from other microvascular beds.
Effect of fluid intake and antihypertensive treatment on cerebral ischemia after subarachnoid hemorrhage.
Authors: Hasan D , Vermeulen M , Wijdicks E F , Hijdra A , van Gijn J
Published: June 2011

We prospectively studied 244 consecutive patients with subarachnoid hemorrhage who were admitted within 72 hours to the same institution between November 1977 and May 1987 and who were not treated with antifibrinolytics. From November 1977 through December 1982 (the first study period), daily fluid intake was 1.5-2.1 and fluid restriction was applied when hyponatremia developed; antihypertensives were administered to all patients with high blood pressure. From January 1983 through April 1987 (the second study period), daily fluid intake was at least 3 l, fluid restriction was not applied, and antihypertensives were administered only when patients were receiving this treatment before admission; calcium antagonists were not administered. Entry variables of the patients admitted during the two study periods were not significantly different, although patients admitted during the second study period were at slightly increased risks of developing cerebral ischemia and of having a poor outcome. Despite this, cerebral ischemia occurred less frequently among patients admitted during the second study period than among those admitted during the first (16 [10%] of 155 patients vs. 19 [21%] of 89 patients; p = 0.030). Overall mortality decreased from 46% to 36% while mortality among patients with cerebral ischemia decreased from 60% to 31% (difference not significant). Rebleeding and acute hydrocephalus occurred with the same frequency among patients admitted during both study periods. We conclude that the combination of increased fluid intake and the avoidance of antihypertensives helps prevent cerebral ischemia after subarachnoid hemorrhage.
Selective cortical neuronal damage after middle cerebral artery occlusion in rats.
Authors: Iizuka H , Sakatani K , Young W
Published: June 2011

We studied histopathologic changes in cerebral cortex of 20 rats after middle cerebral artery occlusion by using the Fink-Heimer suppressive silver impregnation method and conventional stains. At 6 hours after occlusion, Fink-Heimer-stained sections revealed abundant coarsely granular, intensely argyrophilic neurons in the ischemic cortex. These distinctive argyrophilic neurons could be clearly differentiated from neurons that suffered postmortem changes; argyrophilic neurons were present in all layers of the lateral parietal cortex but in only the superficial cortical layers II and III in the parasagittal area of the frontoparietal cortex and the temporo-occipital area. At 24 hours after occlusion as the ischemic region progressed to pannecrosis, argyrophilic neurons were still evident in peri-infarct regions, with more prominent neuritic silver deposits but no changes in number or spatial distribution. Over 2-7 days, the argyrophilic neurons gradually disappeared while many fine silver-impregnated degenerating terminals appeared in the peri-infarct regions. At 3-6 weeks after occlusion, no more argyrophilic neurons were seen in the cortex although degenerating axons were still present in the deep white matter. Our results indicate selective neuronal damage in the superficial cortical layers and massive axonal degeneration in the cerebrum surrounding infarcts. The neuronal damage does not appear to progress beyond 6 hours after middle cerebral artery occlusion. The Fink-Heimer method has many advantages over existing conventional stains for documenting selective neuronal damage in focal cerebral ischemia.
Nimodipine attenuates both increase in cytosolic free calcium and histologic damage following focal cerebral ischemia and reperfusion in cats.
Authors: Uematsu D , Greenberg J H , Hickey W F , Reivich M
Published: June 2011

To clarify the mechanism of its effect on ischemic stroke, we investigated the effect of nimodipine, a dihydropyridine calcium antagonist, on changes in cytosolic free calcium, cortical blood flow, and histologic changes following focal cerebral ischemia and reperfusion in 14 cats. Using indo-1, a fluorescent intracellular Ca2+ indicator, we simultaneously measured changes in the Ca2+ signal ratio (400:506 nm), reduced nicotinamide adenine dinucleotide fluorescence (464 nm), and reflectance (340 nm) during an ultraviolet excitation (340 nm) directly from the cat cortex in vivo. In six cats treated with vehicle only, the calcium signal ratio increased from 5 minutes after middle cerebral artery occlusion to 30 minutes into reperfusion. The elevation of cytosolic free calcium was significantly attenuated by nimodipine, which was administered by intravenous infusion in eight cats starting 5 minutes after occlusion. Nimodipine had no effect on cortical blood flow during ischemia but induced a hyperperfused state following reperfusion. Nimodipine did not modify changes in the mitochondrial oxidation-reduction state. Nimodipine proved to have beneficial effects on recovery of the electroencephalogram following reperfusion as well as on the extent of focal histologic damage. Our results suggest that nimodipine, when administered during the early stage of focal ischemia, can favorably modify the outcome of stroke by reducing the Ca2+ entry during both the ischemic and reperfusion periods.
Conditions for pharmacologic evaluation in the gerbil model of forebrain ischemia.
Authors: Clifton G L , Taft W C , Blair R E , Choi S C , DeLorenzo R J
Published: June 2011

We looked at FiO2, choice of anesthetic, nutritional status, and body temperature in a gerbil model of forebrain ischemia to determine their effect on data interpretation, ischemic outcome, and extent of pharmacologic protection. We subjected 484 gerbils to 5 minutes of forebrain ischemia under different experimental conditions. The gerbils were anesthetized with 3% halothane and inspired 21% O2, 37% O2 and 60% N2O, or 97% O2. Six groups of gerbils pretreated with 200 mg/kg phenytoin or 2 ml/kg polyethylene glycol (vehicle) underwent ischemia in the fasted or fed state. Three groups of gerbils receiving no pretreatment underwent ischemia with rectal temperatures of 32-33 degrees C, 34-35 degrees C, or 37 degrees C. We counted intact neurons in the CA1 hippocampal sector in brains fixed on Day 7 after ischemia. t tests of square-root-transformed cell counts were used to assess the effect of hypothermia, and analysis of variance of the transformed data was used to test for the effects of phenytoin, FiO2, and nutritional status. Phenytoin pretreatment provided significant protection from CA1 neuron loss in all groups tested (p less than 0.001), but the degree of protection varied from 20% to 44%. In spite of significantly higher serum glucose concentrations in fed than in fasted gerbils (173 and 118 mg/dl, respectively), we found no significant effect of nutritional status upon neuron loss in phenytoin- or vehicle-pretreated gerbils. An FiO2 of 21% significantly decreased the number of viable neurons in both vehicle- and phenytoin-pretreated groups (p less than 0.03), despite the lack of an effect of hypoxemia on arterial blood gases.(ABSTRACT TRUNCATED AT 250 WORDS)
Magnetic resonance imaging of ataxic hemiparesis localized to the corona radiata.
Authors: Gutmann D H , Scherer S
Published: June 2011

A 61-year-old woman developed right hemiparesis with homolateral cerebellar-type ataxia. Computed tomography and magnetic resonance imaging demonstrated left corona radiata lesions, not present on magnetic resonance imaging 1 year earlier. No brainstem lesions were identified, suggesting that ataxic hemiparesis can result from lesions in the corona radiata.
Doppler color flow imaging of carotid body tumors.
Authors: Steinke W , Hennerici M , Aulich A
Published: June 2011

Doppler color flow imaging is a new ultrasound method for the simultaneous spatial display of tissue and vessel morphology (B-mode echotomograms) and of color-coded blood flow velocity information (Doppler-mode analysis). This new method is particularly useful in the neck, not only for the assessment of brain arteries but also for the safe and valid identification of carotid paragangliomas compared with other neck tumors. Early clinical detection of carotid paragangliomas is difficult since these lesions often occur sporadically and the patients remain symptom-free until the tumor becomes noticeable. Doppler color flow imaging allows the diagnosis of even small paragangliomas, which may improve management because of existing complications of surgical therapy.
Combination therapy with low-dose aspirin and ticlopidine in cerebral ischemia.
Authors: Uchiyama S , Sone R , Nagayama T , Shibagaki Y , Kobayashi I , Maruyama S , Kusakabe K
Published: June 2011

We compared combination therapy with low-dose aspirin plus ticlopidine to therapy with aspirin alone or ticlopidine alone in patients suffering transient ischemic attack or cerebral infarction. In 17, 24, and 23 patients, respectively, 300 mg/day aspirin, 200 mg/day ticlopidine, and 81 mg/day aspirin plus 100 mg/day ticlopidine were administered orally. Aspirin alone markedly inhibited platelet aggregation induced by arachidonic acid, partially inhibited platelet aggregation induced by adenosine diphosphate, and did not inhibit platelet aggregation induced by platelet activating factor. Ticlopidine alone inhibited platelet aggregation induced by adenosine diphosphate and platelet activating factor, but did not inhibit platelet aggregation induced by arachidonic acid. Combination therapy with aspirin plus ticlopidine markedly inhibited platelet aggregation induced by all three agonists. Plasma concentrations of beta-thromboglobulin and platelet factor 4 remained unchanged by aspirin alone, were slightly reduced by ticlopidine alone, and were markedly reduced by aspirin plus ticlopidine. Plasma concentration of thromboxane B2 was reduced by aspirin alone or with ticlopidine, but not by ticlopidine alone. The level of 6-ketoprostaglandin F1 alpha was reduced only by aspirin alone. Bleeding time was significantly prolonged by aspirin alone and by ticlopidine alone, although the greatest prolongation was produced by aspirin plus ticlopidine. Our results indicate that the combination of aspirin plus ticlopidine is a potent antiplatelet strategy, although the clinical importance of the changes observed need to be determined by a properly designed and controlled prospective study.
Cerebrovascular disease in rural Kashmir, India.
Authors: Razdan S , Koul R L , Motta A , Kaul S
Published: June 2011

We studied the Kuthar Valley in the Anantnag District of south Kashmir (northwestern India) during the year 1986 to ascertain the prevalence and pattern of completed stroke. We detected 91 cases, giving a crude prevalence rate of 143/100,000. However, age-specific prevalence was 41/100,000 in the group aged 15-39 years and 630/100,000 in the group aged greater than or equal to 40 years; 69.23% of the cases were in men. Hypertension was present in 58.24% of the cases, while strokes due to valvular heart disease and puerperium-related strokes were most common in the young. Our study is first of its kind in this part of India.
Stable xenon versus radiolabeled microsphere cerebral blood flow measurements in baboons.
Authors: DeWitt D S , Fatouros P P , Wist A O , Stewart L M , Kontos H A , Hall J A , Kishore P R , Keenan R L , Marmarou A
Published: June 2011

Regional cerebral blood flow was simultaneously determined using the stable xenon computed tomographic and the radioactive microsphere techniques over a wide range of blood flow rates (less than 10-greater than 300 ml/100 g/min) in 12 baboons under conditions of normocapnia, hypocapnia, and hypercapnia. A total of 31 pairs of determinations were made. After anesthetic and surgical preparation of the baboons, cerebral blood flow was repeatedly determined using the stable xenon technique during saturation with 50% xenon in oxygen. Concurrently, cerebral blood flow was determined before and during xenon administration using 15-microns microspheres. In Group 1 (n = 7), xenon and microsphere determinations were made repeatedly during normocapnia. In Group 2 (n = 5), cerebral blood flow was determined using both techniques in each baboon during hypocapnia (PaCO2 = 20 mm Hg), normocapnia (PaCO2 = 40 mm Hg), and hypercapnia (PaCO2 = 60 mm Hg). Xenon and microsphere values in Group 1 were significantly correlated (r = 0.69, p less than 0.01). In Group 2, values from both techniques also correlated closely across all levels of PaCO2 (r = 0.92, p less than 0.001). No significant differences existed between the slopes or y intercepts of the regression lines for either group and the line of identity. Our data indicate that the stable xenon technique yields cerebral blood flow values that correlate well with values determined using radioactive microspheres across a wide range of cerebral blood flow rates.
Diagnostic significance of flow separation in the carotid bulb.
Authors: Nicholls S C , Phillips D J , Primozich J F , Lawrence R L , Kohler T R , Rudd T G , Strandness D E
Published: June 2011

Pulsatile blood flow within the normal carotid sinus involves at least two distinct components. That near the flow divider is laminar and antegrade, whereas a boundary layer separation zone in the posterolateral aspect exhibits transient blood flow reversal. It is now possible to document these flow velocity components using pulsed Doppler ultrasound methods. When atherosclerosis develops, it preferentially involves the posterolateral bulb region, obliterating the normal configuration of the sinus with consequent loss of the flow separation zone. It was therefore hypothesized that if flow separation could be detected, it should be predictive of a normal angiogram. To assess this, we evaluated 20 symptomatic patients and two with only bruits found by duplex scanning to have flow separation in either one or both carotid bulbs and who also underwent cerebral angiography. Initial diagnoses were stroke in seven, reversible ischemic neurologic deficit in one, transient ischemic attack in 12, and bruit in two. Flow separation was bilateral in 13 patients (59%). There were 15 patients with symptoms in the territory of a carotid bulb exhibiting flow separation. By angiography, of the 35 bulbs with boundary layer separation, 27 (77%) were normal, with the remainder showing lesions that reduced the diameter of the vessel by 20% or less. Final diagnoses of the 15 patients with symptoms ipsilateral to a carotid sinus exhibiting flow separation were fibromuscular disease in two, lacunar stroke in three, dissection in two, subclavian steal in one, cardiogenic embolus in three, migraine in one, hyperventilation syndrome in one, kink of the mid-internal carotid artery in one, and no diagnosis in one.(ABSTRACT TRUNCATED AT 250 WORDS)
Nicardipine reduces ischemic brain injury. Magnetic resonance imaging/spectroscopy study in cats.
Authors: Kucharczyk J , Chew W , Derugin N , Moseley M , Rollin C , Berry I , Norman D
Published: June 2011

We investigated whether the calcium channel entry blocker nicardipine would reduce ischemic brain damage in barbiturate-anesthetized cats subjected to permanent unilateral occlusion of the middle cerebral artery. The evolution of cerebral injury was assessed in vivo in 24 cats by a combination of proton magnetic resonance imaging and phosphorus-31 magnetic resonance spectroscopy for 5 hours following occlusion. Immediately thereafter, the volume of histochemically ischemic brain tissue was determined planimetrically in triphenyl tetrazolium chloride-stained serial coronal sections. Nicardipine was initially administered as an intravenous bolus injection of 10 mg/kg/hr 15 minutes before or 15 minutes after occlusion, followed by continuous infusion at 8 mg/kg/hr for the 5 hours of the experiment. Compared with untreated controls, cats that received nicardipine before or after occlusion showed a significant reduction in the extent of edema in the ipsilateral cerebral cortex, internal capsule, and basal ganglia. The results of phosphorus-31 magnetic resonance spectroscopy studies suggest that nicardipine may protect against cerebral ischemic damage by an action on cellular metabolic processes that preserve high-energy phosphates during the ischemic period.
Effect of nimodipine on cerebral blood flow and metabolism in rats during hyperventilation.
Authors: Young W L , Chien S
Published: June 2011

Nimodipine shws promise in the prevention and treatment of brain ischemia. We examined the interaction of nimodipine pretreatment in a dose sufficient to prevent postischemic hypoperfusion and hyperventilation. We studied four groups of rats: normocarbia plus vehicle (Group 1, n = 5), hypocarbia plus vehicle (Group 2, n = 4), normocarbia plus nimodipine (Group 3, n = 7), and hypocarbia plus nimodipine (Group 4, n = 6). Groups 3 and 4 received 1 mg/kg i.p. nimodipine, and Groups 1 and 2 received an equivalent amount of vehicle. Ventilation was left unaltered in Groups 1 and 3 or increased to lower PaCO2 to 21-24 mm Hg in Groups 2 and 4. Determination of regional cerebral glucose utilization (rCGU) was carried out using the [3H]2-deoxyglucose method, and regional cerebral blood flow (rCBF) was determined by the indicator fractionation method using [14C]iodoantipyrine. The brain regions studied were the cerebral hemispheres, the diencephalon, the cerebellum, and the brainstem. Hyperventilation in Groups 2 and 4 from approximately 38 to 22 mm Hg reduced rCBF to 60% of normocarbic levels (p less than 0.05). The slope and intercept of this response were similar in vehicle- and nimodipine-pretreated rats. Nimodipine modestly decreased mean arterial blood pressure by 20% and increased plasma glucose concentration by 60% (p less than 0.05). Although nimodipine tended to increase rCBF and decrease regional cerebrovascular resistance (rCVR), this was significant only for hemispheric rCVR (p less than 0.05). There was a borderline effect for nimodipine to increase rCGU, especially during hypocarbia.(ABSTRACT TRUNCATED AT 250 WORDS)
An alternative view of heparin anticoagulation in acute focal brain ischemia.
Authors: Phillips S J
Published: June 2011

Despite the lack of evidence of its efficacy, heparin therapy has been recommended for selected patients with ischemic stroke syndromes. However, heparin has procoagulant effects on platelet function and a propensity to produce serious side effects. When these factors are considered, heparin loses its appeal as a therapeutic agent for patients with acute focal cerebral ischemia.
Differences in mortality and cardiovascular morbidity during a 3-year follow-up of transient ischemic attacks and minor strokes.
Authors: Falke P , Stavenow L , Young M , Lindgärde F
Published: June 2011

We prospectively followed 78 patients with transient ischemic attacks (TIAs) from the carotid artery territory and 45 patients with minor ischemic strokes for 3 years. The mean +/- SD age of the patients in the TIA group was 66.9 +/- 7.9 years compared with 68.8 +/- 6.7 in the minor stroke group. Mortality among the TIA patients was significantly higher than that among minor stroke patients (18 of 78 compared with two of 45, p less than 0.01); mortality in the minor stroke group was not higher than that in the background population, whereas mortality in the TIA group was almost twice as high. The most common cause of death in the TIA group was myocardial infarction, and morbidity due to myocardial infarction and new TIA was higher in the TIA group than in the minor stroke group (35 events compared with seven), whereas no difference was found regarding stroke (five strokes compared with eight). Preexisting vascular disease implied an increased risk of mortality and morbidity in the TIA group. We conclude that carotid-territory TIA indicates a worse prognosis than minor stroke as mortality is higher in TIA patients at the same preexisting vascular disease prevalence and stroke frequency.
Effect of insulin on acute experimental cerebral ischemia in gerbils.
Authors: Fukuoka S , Yeh H , Mandybur T I , Tew J M
Published: June 2011

We studied the effects of insulin with and without food deprivation on experimental cerebral ischemia in 197 gerbils. Ischemia was induced by unilateral common carotid artery occlusion for 4 hours. Gerbils were divided into four experimental groups and were studied for up to 1 week of survival: Group A (n = 50) was fed but received no insulin, Group B (n = 50) was deprived of food for 24 hours before surgery but received no insulin, Group C (n = 49) was fed and received daily injections of 0.1 IU lente insulin for 3 days before surgery, and Group D (n = 48) was deprived of food and received daily insulin injections. Insulin treatment was continued in Groups C and D after surgery. Blood glucose levels of all gerbils were determined before treatment (overall mean +/- SEM 88.0 +/- 12.4 mg/dl) and before carotid artery occlusion (Group A 92.2 +/- 18.3 mg/dl, Group B 81.4 +/- 11.7 mg/dl [p less than 0.05 different from before treatment], Group C 92.8 +/- 22.3 mg/dl, and Group D 66.1 +/- 24.0 mg/dl [p less than 0.001 different from before treatment]). Among the four groups, 52 gerbils died within 1 week. Neurologic deficits were scored and histologic evidence of the infarcts was graded in survivors at 1 week. Group C gerbils had the best stroke index scores. Histologic evaluation revealed that 35.9% of Group A, 21.1% of Group B, 13.9% of Group C (p less than 0.05 compared with Group A), and 28.1% of Group D survivors developed cerebral infarcts.(ABSTRACT TRUNCATED AT 250 WORDS)
Sarcoidosis presenting with stroke.
Authors: Brown M M , Thompson A J , Wedzicha J A , Swash M
Published: June 2011

A 25-year-old black man with sarcoidosis presented with transient ischemic attacks followed by sudden, persistent right hemiparesis. He gave a history of recent, recurrent lower motor neuron facial palsy. Computed tomography demonstrated an infarct in the left internal capsule. Chest x-ray film showed bilateral hilar and mediastinal lymphadenopathy and multiple opacities in the lung fields. Serum angiotensin converting enzyme concentration was raised, and a Kveim test was positive for sarcoidosis. Despite clear pathologic reports of cerebral vasculitis in neurosarcoidosis, the occurrence of stroke is extremely rare.
Cerebral cortical and white matter reactivity to carbon dioxide.
Authors: Reich T , Rusinek H
Published: June 2011

We measured cerebrovascular reactivity to carbon dioxide in the cerebral cortex and the subcortical white matter of 12 healthy adult volunteers (four young subjects aged 21-24, four middle-aged subjects aged 34-40, and four elderly subjects aged 62-85 years). Blood flow was computed from the concentration history of xenon-133 in the volume of interest measured with an ultrapure germanium detector array. End-tidal PaCO2 ranged from 35.4 to 42.6 mm Hg. The mean +/- SD baseline blood flows in the cerebral cortex were 60 +/- 7, 51 +/- 9, and 33 +/- 4 ml/100 cm3/min in the young, the middle-aged, and the elderly subjects, respectively; the corresponding subcortical white matter baseline blood flows were 21 +/- 1, 22 +/- 3, and 16 +/- 5 ml/100 cm3/min. Mean +/- SD cerebrovascular reactivities to carbon dioxide in the cerebral cortex were 2.03 +/- 0.58, 1.36 +/- 0.41, and 0.72 +/- 0.19 ml/100 cm3/min/mm Hg PaCO2 for the young, the middle-aged, and the elderly subjects, respectively; the corresponding reactivities in the subcortical white matter were 0.69 +/- 0.11, 0.59 +/- 0.17, and 0.36 +/- 0.41 ml/100 cm3/min/mm Hg PaCO2. Blood flow and cerebrovascular reactivity in the cerebral cortex of the young subjects were significantly higher than those for white matter and significantly higher than those in the elderly subjects (p less than 0.001). Age vs. blood flow (for the cortex) and age vs. cerebrovascular reactivity (for both cortical gray and subcortical white matter) also showed significant linear correlation (p less than 0.05). However, the age-related changes in white matter blood flow and cerebrovascular reactivity were slow, and the differences among the age groups were not statistically significant.
Age-dependent vulnerability of brain choline acetyltransferase activity to transient cerebral ischemia in rats.
Authors: Nyberg P , Waller S
Published: June 2011

Male Fischer-344 rats aged 6, 12, or 24 months were subjected to four-vessel occlusion cerebral ischemia to assess age-dependent ischemic vulnerability of cholinergic and GABAergic neurons based on choline acetyltransferase (EC 2.3.1.6) and glutamic acid decarboxylase (EC 4.1.1.15) activities. Activities of both enzymes were similar (p greater than 0.05) in 6- (n = 5) and 12- (n = 5) month-old rats. Mean +/- SEM choline acetyltransferase activities in the cortex, hippocampus, striatum, and cerebellum of 6-month-old controls were 75 +/- 5, 123 +/- 9, 415 +/- 9, and 50 +/- 4 nmol acetylcholine/hr/mg protein, respectively, and were 20-30% lower (p less than 0.05) in all brain regions except the cerebellum in 24-month-old controls. Choline acetyltransferase activity was unaffected by ischemia in 6- and 12-month-old rats but was reduced by 30-60% in 24-month-old rats. Mean +/- SEM glutamic acid decarboxylase activities in the cortex, hippocampus, striatum, and cerebellum of 6-month-old controls were 98 +/- 8, 86 +/- 7, 144 +/- 13, and 125 +/- 9 nmol gamma-aminobutyric acid/hr/mg protein, respectively, and 25-35% lower in all regions of 24-month-old controls. After 30 minutes of ischemia and 5 days of recovery, glutamic acid decarboxylase activities were reduced (p less than 0.05) in all brain regions and age groups. However, its activity was decreased (p less than 0.05 compared with age-matched controls) by 55% in the cortex and 79% in the hippocampus of 24-month-old rats compared with 30% and 45% in younger rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of therapy on platelet activating factor-induced aggregation in acute stroke.
Authors: Joseph R , Welch K M , D'Andrea G
Published: June 2011

Platelet activating factor, a potent inducer of in vivo platelet activation and thrombosis, has been shown to be excessively active in acute ischemic stroke patients. Therefore, we studied the effect of aspirin/dipyridamole therapy in inhibiting platelet activating factor-induced platelet activation in acute ischemic stroke patients, 23 taking aspirin/dipyridamole and 21 untreated. Aspirin/dipyridamole-treated patients failed to show suppression of platelet activating factor-induced platelet aggregation even though collagen-induced activation was inhibited, suggesting that platelet activating factor acts by cyclooxygenase-independent mechanisms. Failure to suppress cyclooxygenase-independent mechanisms of platelet activation may explain the limited usefulness of current antiplatelet therapy, aspirin in particular, in stroke prevention. The role of selective platelet activating factor antagonists both in isolation and combined with aspirin needs to be investigated for their usefulness in the treatment and prevention of ischemic stroke.
Selective platelet deposition during focal cerebral ischemia in cats.
Authors: Jafar J J , Menoni R , Feinberg H , LeBreton G , Crowell R M
Published: June 2011

Platelet deposition in the microcirculation may play a role in focal cerebral ischemia. We investigated platelet deposition in selected parts of the cat brain after temporary middle cerebral artery occlusion. Ten anesthesized cats were given autologous indium-111-labeled platelets and chromium-51-labeled erythrocytes. The right middle cerebral artery was occluded with miniature aneurysm clips for 3 hours via a transorbital approach; blood pressure was reduced concomitantly to decrease the collateral circulation. Removal of the clips initiated a 45-minute period of normotensive reperfusion. After sacrifice, the brain was removed and sectioned for comparison of right- versus left-hemisphere platelet deposition. Platelets were selectively deposited in the territory of the occluded right middle cerebral artery. Significant deposition was found in the caudate nucleus, internal capsule, parietal cortex, and the centrum semiovale. Our findings support the evidence that platelets are deposited in the microvasculature during temporary severe focal cerebral ischemia.
Acute anticoagulation following cardioembolic stroke.
Authors: Rothrock J F , Dittrich H C , McAllen S , Taft B J , Lyden P D
Published: June 2011

Whether acute anticoagulation after cardioembolic stroke affords substantial protection against early recurrent emboli or an unacceptable risk of hemorrhage remains controversial. To assess this further, we evaluated 121 consecutive patients with acute cardioembolic stroke. Forty-nine were therapeutically anticoagulated within 96 hours of stroke onset, and 41 received no anticoagulants within the first 2 weeks after stroke. These two groups did not differ significantly with regard to age, sex, severity of acute neurologic deficit, or spectrum of underlying cardiac disease. The incidences of clinically significant brain hemorrhage (2%) and early recurrent embolization (2%) were equally low in both groups. Our data suggest that acute acute anticoagulation may be employed safely in most patients with cardioembolic stroke but that such treatment does not clearly benefit this population as a whole.
Early collateral blood supply and late parenchymal brain damage in patients with middle cerebral artery occlusion.
Authors: Bozzao L , Fantozzi L M , Bastianello S , Bozzao A , Fieschi C
Published: June 2011

We angiographically studied 80 patients within 6 hours after the onset of ischemic supratentorial infarction. From this group we selected 36 patients with middle cerebral artery occlusion who survived. In these 36 patients, we compared the presence of a collateral blood supply during the early phase with the extent of final parenchymal brain damage obtained by computed tomography 3 months after the event. The presence of a collateral circulation during the first few hours after the stroke reduced the size of the final parenchymal brain damage in patients with middle cerebral artery stem-trunk occlusion. The collateral blood supply was more efficient in patients who had no significant stenosing lesions of the extracranial internal carotid artery. Our data confirm that the lenticulostriate arteries are end arteries not supplied by collateral blood vessels and suggest that lesions formerly thought to be caused by hemodynamic mechanisms (watershed infarcts) or arteriolar lesions (lacunar infarcts) may be due to middle cerebral artery occlusions.
Alcohol use and subsequent cerebrovascular disease hospitalizations.
Authors: Klatsky A L , Armstrong M A , Friedman G D
Published: June 2011

We studied the relations between reported alcohol use and the incidence of hospitalization for several types of cerebrovascular disease. Daily consumption of three or more drinks, but not lighter drinking, was related to higher hospitalization rates for hemorrhagic cerebrovascular disease, especially intracerebral hemorrhage. Age, blood pressure, and black race were other independent predictors of hemorrhagic events; higher blood pressure appeared to be a partial mediator of the relation between alcohol use and hemorrhagic events. Alcohol use was associated with lower hospitalization rates for occlusive cerebrovascular disease; an inverse relation was present in both sexes, whites and blacks, and for extracranial and intracerebral occlusive lesions. Other predictors of hospitalization for occlusive disease included age, blood pressure, smoking, blood glucose and total cholesterol concentrations, and baseline disease. Our data suggest that heavier drinking increases the risk of hemorrhagic cerebrovascular events, but that alcohol use may lessen the risk of occlusive lesions.
Cerebral blood flow determination within the first 8 hours of cerebral infarction using stable xenon-enhanced computed tomography.
Authors: Hughes R L , Yonas H , Gur D , Latchaw R
Published: June 2011

Cerebral blood flow mapping with stable xenon-enhanced computed tomography (Xe/CT) was performed in conjunction with conventional computed tomography (CT) within the first 8 hours after the onset of symptoms in seven patients with cerebral infarction. Six patients had hemispheric infarctions, and one had a progressive brainstem infarction. Three patients with very low (less than 10 ml/100 g/min) blood flow in an anatomic area appropriate for the neurologic deficit had no clinical improvement by the time of discharge from the hospital; follow-up CT scans of these three patients confirmed infarction in the area of very low blood flow. Three patients with moderate blood flow reductions (15-45 ml/100 g/min) in the appropriate anatomic area had significant clinical improvement from their initial deficits and had normal follow-up CT scans. One patient studied 8 hours after stroke had increased blood flow (hyperemia) in the appropriate anatomic area and made no clinical recovery.
Calcium dependence of intracerebral arteriolar vasomotor tone and constrictor responses in rats.
Authors: Takayasu M , Dacey R G
Published: June 2011

The purpose of our study was to determine in rats the dependence of constrictor responses of intracerebral (parenchymal) penetrating arterioles on extracellular calcium. Vessel diameter was monitored in vitro, after spontaneous tone had developed. When the organ bat solution was changed from a physiological solution to a Ca2+-free one containing 0.5 mM EGTA, these vessels showed rapid and marked vasodilation to a mean +/- SEM of 159.8 +/- 8.2% of control (p = 0.018). After 3 minutes of pretreatment with Ca2+-free solution, constrictor responses to solutions of 140 mM KCl, pH 8.0, or 10(-4) M prostaglandin F2 alpha, were completely abolished, except for small transient contractions with the latter (6.6 +/- 1.8%). When vasoconstrictors were applied simultaneously with the Ca2+-free solution, all vessels still dilated to 159.8 +/- 8.4% (KCl), 146.7 +/- 6.1% (pH 8.0), and 124.3 +/- 9.1% (prostaglandin 2 alpha) of control (p = 0.018). Our results suggest that both vasomotor tone and constrictor responses in intracerebral arterioles are highly dependent upon activation from an extracellular calcium source.
First-year results of a community-based study of stroke incidence in Umbria, Italy.
Authors: Ricci S , Celani M G , Guercini G , Rucireta P , Vitali R , La Rosa F , Duca E , Ferraguzzi R , Paolotti M , Seppoloni D
Published: June 2011

The SEPIVAC study (Italian initials for "epidemiologic study of incidence of acute cerebrovascular disease") is a community-based epidemiologic survey of incidence and outcome of cerebrovascular disease in the territory of the 6th Local Health Unit, Umbria, Italy, where 49,101 people live. All cases were registered with the study either by notification from general practitioners or by check of hospital admission within the study area and in the two hospitals of Perugia. Death certificates were looked at as well. Patients were registered with the study when the clinical picture fulfilled the definition of stroke and transient ischemic attack (TIA) adopted for this study. Patients were followed up at approximately 30 days and 6 months. During the first year of the study (September 1, 1986 to August 31, 1987), 189 cases were registered: 108 suffered a "first ever in a lifetime" stroke, 30 a recurrent stroke, and 51 a "first ever in a lifetime" transient ischemic attack. Sixty-one percent of patients (71% of first strokes) had a computed tomography scan. For our study, the crude annual incidence rate of first stroke was 2.2 per 1,000 (confidence intervals 1.81-2.66); the standardized rate to the European population was 1.36 (confidence intervals 1.06-1.74). At least 83% of first strokes were due to cerebral ischemia; in 26 cases a clinical diagnosis of lacunar ischemia was made. The 30-day case fatality rate was 21%; 25% of our patients had recovered completely or almost completely after 1 month.
Measurements of acute cerebral infarction: lesion size by computed tomography.
Authors: Brott T , Marler J R , Olinger C P , Adams H P , Tomsick T , Barsan W G , Biller J , Eberle R , Hertzberg V , Walker M
Published: June 2011

As part of a prospective therapy study of 65 patients with acute, nonhemorrhagic, cerebral infarction, computed tomographic scans of the head were obtained at admission, 7-10 days, and 3 months. The scans were analyzed for the presence, site, size, and volume measurement of the infarction. At 7-10 days, the mean infarction volume as measured by computed tomography was 55 cm3 or about 4 x 4 x 3.5 cm (range = 0-507 cm3). At 3 months, the mean infarction volume decreased by 25% to 41 cm3. For the 26 scans showing infarction at the time of admission, the mean lesion volume was 33 cm3 at admission, 51 cm3 at 7-10 days, and 49 cm3 at 3 months. With lesion size at 7-10 days expressed as percentage of total brain volume, the mean infarction size was only 5%. Of the 49 patients with lesions revealed by computed tomography at 7-10 days, 20 had an infarction of 1% or less of total brain volume, while only six had an infarction of 20% or more of total brain volume. The lesion volumes as measured by the 7-10-day computed tomography correlated with the neurologic examination scores on admission (Spearman's rank-order correlation = 0.78) and with the scores at 1 week (Spearman's rank-order correlation = 0.79).
Hemodynamic and metabolic effects of cerebral arteriovenous malformations studied by positron emission tomography.
Authors: Tyler J L , Leblanc R , Meyer E , Dagher A , Yamamoto Y L , Diksic M , Hakim A
Published: June 2011

Seventeen patients with an intracranial arteriovenous malformation were studied with positron emission tomography. Cerebral blood flow, cerebral blood volume, oxygen extraction fraction, and glucose and oxygen metabolism were evaluated in both hemispheres, excluding the area of the malformation itself. Patients were divided into three groups according to the size of their malformation, and results obtained were compared with studies in healthy volunteers. The glucose metabolism was significantly (p less than 0.01) decreased in the ipsilateral hemisphere in all patients. The cerebral blood volume was significantly increased (p less than 0.001) ipsilaterally in the three groups, and contralaterally in patients with medium- and large-sized arteriovenous malformations. The cerebral blood volume to cerebral blood flow ration, an index of vascular mean transit time, was significantly increased (p less than 0.005) ipsilaterally in patients with medium- and large-sized malformations and contralaterally in patients with large ones. Cerebral blood flow, oxygen extraction fraction, and oxygen metabolism were within the normal range bilaterally in all three groups, but oxygen extraction fraction tended to be higher in patients with larger lesions. The lack of significant change in oxygen metabolism suggests that oxygen metabolism in cortical areas remote from the arteriovenous malformation has been maintained by compensatory hemodynamic mechanisms. These data reveal widespread metabolic and hemodynamic consequences of arteriovenous malformations and suggest that they are associated with impairment of glucose metabolism, both in ipsilateral regions remote from the lesion and in the contralateral hemisphere in patients with large lesions.
Comparison of cerebral angiography and transcranial Doppler sonography in acute stroke.
Authors: Zanette E M , Fieschi C , Bozzao L , Roberti C , Toni D , Argentino C , Lenzi G L
Published: June 2011

We compared digital intra-arterial angiography and transcranial Doppler sonography in acute cerebral ischemia as part of a wider study on a continuous series of 48 patients with acute focal cerebral ischemia in the carotid territory, observed within 4 hours of the onset of symptoms. The most significant Doppler findings of the middle cerebral artery included no detection of the artery when occlusion of the carotid siphon or the middle cerebral artery at its origin was shown by angiography and reduced flow velocities and asymmetry (symptomatic less than asymptomatic) when the occlusion was located in the terminal tract of the middle cerebral artery mainstem or in numerous terminal branches. Higher flow velocities in the anterior cerebral artery or posterior cerebral artery, mostly in the symptomatic hemisphere, often accompanied middle cerebral artery pathology, probably indicating collateral compensatory pathways.
Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain.
Authors: Busto R , Globus M Y , Dietrich W D , Martinez E , Valdés I , Ginsberg M D
Published: June 2011

We have demonstrated previously that mild intraischemic hypothermia confers a marked protective effect on the final histopathological outcome. The present study was carried out to evaluate whether this protective effect involves changes in the degree of local cerebral blood flow reductions, tissue accumulation of free fatty acids, or alterations in the extracellular release of glutamate and dopamine. Rats whose intraischemic brain temperature was maintained at 36 degrees C, 33 degrees C, or 30 degrees C were subjected to 20 minutes of ischemia by four-vessel occlusion combined with systemic hypotension. Levels of local cerebral blood flow, as measured autoradiographically, were reduced uniformly in all experimental animals at the end of ischemia by gas chromatography after tissue extraction and separation by thin layer chromatography. A massive ischemia-induced accumulation of individual free fatty acids was observed in animal groups whose intraischemic brain temperature was maintained at either 36 degrees C or 30 degrees C. Extracellular neurotransmitter levels were measured by microdialysis; the perfusate was collected before, during, and after ischemia. In rats whose intraischemic brain temperature was maintained at 36 degrees C, dopamine and glutamate increased significantly during ischemia and the early period of recirculation (by 500-fold and sevenfold, respectively). In animals whose brain temperature was maintained at 33 degrees C and 30 degrees C, the release of glutamate was completely inhibited, and the release of dopamine was significantly attenuated (by 60%). These results suggest that mild intraischemic hypothermia does not affect the ischemia-induced local cerebral blood flow reduction or free fatty acid accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased lipid peroxidation in vulnerable brain regions after transient forebrain ischemia in rats.
Authors: Bromont C , Marie C , Bralet J
Published: June 2011

We examined cerebral lipid peroxidation, estimated by a thiobarbituric acid test, in rat brain regions after 30 minutes of severe forebrain ischemia and at recirculation periods of up to 72 hours. The lipid peroxide levels remained unaltered in all brain regions during ischemia and during the first hour of recirculation but were selectively increased between 8 and 72 hours of recirculation in the ischemia-sensitive regions of the hippocampus, striatum, and cortex. The most pronounced increases (30-37%) were seen at 48 hours of recirculation. In contrast, lipid peroxide levels were unchanged in infarcted brain regions 24 hours after intracarotid injection of microspheres, indicating that reoxygenation of the ischemic brain is a prerequisite for lipid peroxidation. We assessed the lipid peroxidation capacity of cerebral homogenates obtained from rats subjected to ischemia and recirculation by measuring the production of lipid peroxides after aerobic incubation. The homogenates from rats exposed to 30 minutes of ischemia or to 1 hour of recirculation were not more susceptible to peroxidation. However, the production of lipid peroxides was selectively increased in the hippocampus, striatum, and cortex at 8-48 hours of recirculation, suggesting a loss of efficacy of the antioxidant systems. These results, showing a delayed and long-lasting increase in lipid peroxidation that occurs in ischemia-sensitive brain regions and parallels the development of neuronal necrosis, support the hypothesis that free radical processes participate in postischemic neuronal damage.
Effect of cyclooxygenase and lipoxygenase inhibitors on delayed neuronal death in the gerbil hippocampus.
Authors: Nakagomi T , Sasaki T , Kirino T , Tamura A , Noguchi M , Saito I , Takakura K
Published: June 2011

The purpose of our study was to examine whether cyclooxygenase and lipoxygenase inhibitors ameliorate delayed neuronal death in the hippocampal CA1 sector in Mongolian gerbils after 5 minutes of forebrain ischemia. Gerbils were injected intraperitoneally with cyclooxygenase inhibitors piroxicam and flurbiprofen or with lipoxygenase inhibitors AA-861 and BW-755C. Seven days after ischemic insult, the animals were perfusion-fixed, and the neuronal density in the hippocampal CA1 sector was estimated. The average neuronal density in unoperated normal gerbils was 247 +/- 9/mm (mean +/- SEM). In ischemic gerbils with vehicle administration, the average neuronal densities were 13 +/- 2, 14 +/- 2, 13 +/- 2, and 13 +/- 1 for piroxicam, flurbiprofen, AA-861, and BW-755C, respectively. The average neuronal densities in ischemic gerbils treated with 1.5 and 10 mg/kg piroxicam and 1.5 and 10 mg/kg flurbiprofen were 13 +/- 2, 194 +/- 9, 19 +/- 5, and 143 +/- 12, respectively. In ischemic gerbils treated with 15 and 100 mg/kg AA-861 and 30 mg/kg BW-755C, the average neuronal densities were 12 +/- 1, 13 +/- 1, and 14 +/- 2, respectively. At their higher doses, both piroxicam and flurbiprofen significantly (p less than 0.01) ameliorated delayed neuronal death in the hippocampal CA1 sector. Our results suggest that cyclooxygenase products play an important role in the development of delayed neuronal injury after cerebral ischemia.
Brain perfusion in acute and chronic hyperglycemia in rats.
Authors: Kikano G E , LaManna J C , Harik S I
Published: June 2011

Recent studies show that acute and chronic hyperglycemia cause a diffuse decrease in regional cerebral blood flow and that chronic hyperglycemia decreases the brain L-glucose space. Since these changes can be caused by a decreased density of perfused brain capillaries, we used 30 adult male Wistar rats to study the effect of acute and chronic hyperglycemia on 1) the brain intravascular space using radioiodinated albumin, 2) the anatomic density of brain capillaries using alkaline phosphatase histochemistry, and 3) the fraction of brain capillaries that are perfused using the fluorescein isothiocyanate-dextran method. Our results indicate that acute and chronic hyperglycemia do not affect the brain intravascular space nor the anatomic density of brain capillaries. Also, there were no differences in capillary recruitment among normoglycemic, acutely hyperglycemic, and chronically hyperglycemic rats. These results suggest that the shrinkage of the brain L-glucose space in chronic hyperglycemia is more likely due to changes in the blood-brain barrier permeability to L-glucose.