bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of nicardipine on cerebral vascular responses to hypocapnia and blood flow velocity in the middle cerebral artery.
Authors: Kawaguchi M , Furuya H , Kurehara K , Yamada M
Published: June 2011

We noninvasively evaluated the effects of nicardipine on cerebral vascular responses to hypocapnia and blood flow velocity in the middle cerebral artery of 10 patients aged 17-60 (mean +/- SD 46.1 +/- 11.8) years. During fentanyl/diazepam/nitrous oxide anesthesia, mean blood flow velocity in the middle cerebral artery was measured and cerebral vascular reactivity to hypocapnia induced by hyperventilation was assessed before and during the administration of nicardipine. Mean blood flow velocity was measured using transcranial Doppler ultrasonography, and the cerebral vascular reactivity was expressed as the percentage change in mean blood flow velocity per unit change in end-tidal PCO2. During the administration of 5.1 +/- 1.3 micrograms/kg/min nicardipine, which caused a 26% reduction in mean arterial blood pressure, mean blood flow velocity increased significantly from 57.2 +/- 19.2 to 64.2 +/- 21.6 cm/sec (p less than 0.01, paired t test), whereas cerebral vascular reactivity showed no significant change (4.0 +/- 1.2% and 4.9 +/- 2.5%, respectively). In conclusion, during fentanyl/diazepam/nitrous oxide anesthesia in patients, cerebral vascular reactivity to hypocapnia was maintained and nicardipine-induced hypotension resulted in increased middle cerebral artery blood flow velocity with maintenance of carbon dioxide reactivity to hypocapnia.
Activation of the protein kinase C-mediated contractile system in canine basilar artery undergoing chronic vasospasm.
Authors: Matsui T , Sugawa M , Johshita H , Takuwa Y , Asano T
Published: June 2011

We previously suggested that activation of the protein kinase C-mediated contractile system may participate in the occurrence of chronic cerebral vasospasm. In the present study, we compared segments of normal beagle basilar arteries in vitro with segments of arteries undergoing chronic vasospasm to determine the responsiveness to various agonists such as serotonin, prostaglandin F2 alpha, and phorbol 12,13-diacetate as well as to external Ca2+. We also compared the effects of W-7 (a calmodulin inhibitor), nicardipine (a calcium channel blocker), and H-7 (a protein kinase C inhibitor) on the spontaneous tonus of arterial segments stabilized at a resting tension of 3 g. Compared with normal segments, the responsiveness to each agonist in segments undergoing vasospasm was essentially unchanged whereas the the responsiveness to external Ca2+ was significantly decreased (p less than 0.001). In segments undergoing vasospasm the decrease in resting tension induced by W-7 was markedly diminished (p less than 0.01), that induced by nicardipine was unchanged, and that induced by H-7 was significantly increased (p less than 0.01). Our results indicate that spontaneous tonus due to activation of the protein kinase C system is significantly augmented in segments undergoing vasospasm. Thus this system, rather than the Ca2+/calmodulin system, appears to play a major role in the occurrence of chronic vasospasm.
Hypothermia reduces 72-kDa heat-shock protein induction in rat brain after transient forebrain ischemia.
Authors: Chopp M , Li Y , Dereski M O , Levine S R , Yoshida Y , Garcia J H
Published: June 2011

We examined the influence of concurrent moderate hypothermia (30 degrees C) and transient forebrain ischemia on the induction of 72-kDa heat-shock protein and neuronal damage in male Wistar rats.

Experimental groups included: normothermic with 8 minutes of transient forebrain ischemia (group 1, n = 7), hypothermic without ischemia (group 2, n = 9), and hypothermic (30 degrees C) with 8 minutes of transient forebrain ischemia (group 3, n = 5). Intense 72-kDa heat-shock protein immunoreactivity was demonstrated in rat forebrain 48 hours after induction of normothermic forebrain ischemia (group 1); it was not detected in the brain of animals subjected to hypothermia without ischemia (group 2), and hypothermia during ischemia (group 3) significantly inhibited its expression compared with that in normothermic ischemia animals (group 1).

These observations suggest that 72-kDa heat-shock protein induction is not the mechanism by which moderate hypothermia protects against ischemic cell damage.
Cerebral infarction associated with protein C deficiency.
Authors: Matsushita K , Kuriyama Y , Sawada T , Uchida K
Published: June 2011

A deficiency of plasma protein C, both the hereditary and acquired types, is one cause of thromboembolic disease. Several antineoplastic agents have been reported to decrease the production of protein C in the liver by impairing either the absorption or metabolism of vitamin K, leading to acquired protein C deficiency.

We treated a young woman with protein C deficiency, who had developed a cerebral infarction of the right parietal cortex of sudden onset. On admission, the antigenic level of plasma protein C was 38%. Serial cerebral angiography revealed occlusion of the right middle cerebral artery, which subsequently recanalized completely. This patient had taken fluorouracil derivatives orally for as long as 3 years following a left mastectomy for stage II breast cancer. Tests revealed that the patient's mother had only one-half the normal activity of plasma protein C despite a normal antigenic level.

We speculate that the etiology of the cerebral infarction in this patient might involve an embolic mechanism associated with protein C deficiency induced by an interaction between inherited and acquired factors.
Granulocyte adhesion, deformability, and superoxide formation in acute stroke.
Authors: Grau A J , Berger E , Sung K L , Schmid-Schönbein G W
Published: June 2011

Impaired rheological properties of as well as cytotoxic substances produced by granulocytes may contribute to tissue damage in acute ischemic stroke. To assess changes in the properties of circulating granulocytes, we measured their adhesion, deformability, and superoxide generation in the first 3 days after ischemic stroke.

Granulocytes from 18 male patients and 20 age- and risk-matched controls were investigated. Adhesion to murine laminin-, human fibronectin-, and bovine serum albumin-coated surfaces was measured with and without the stimulus phorbol myristate acetate and the antiadhesion antibody IB4. Superoxide anion formation was assessed by the reduction of ferricytochrome C. In a subgroup of 10 patients and 11 controls, granulocyte deformability was determined using the micropipette aspiration technique.

The patients had significantly greater granulocyte adhesion to laminin (p less than 0.005) and fibronectin (p less than 0.05) but not bovine serum albumin. Cell stimulation enhanced the differences between the groups, whereas the antiadhesion antibody inhibited adhesion in both patients and controls. There were no significant differences in granulocyte deformability. Superoxide production by granulocytes was significantly lower in the patients without the stimulus (p less than 0.05) and with 10 nM phorbol myristate acetate (p less than 0.005).

These findings suggest that circulating granulocytes in ischemic stroke exhibit increased adhesive properties, a feature that represents one of the risk factors for granulocyte entrapment, impairment of microvascular flow, and tissue injury.
Sustained damage to energy metabolism of brain regions after microsphere embolism in rats.
Authors: Takeo S , Taguchi T , Tanonaka K , Miyake K , Horiguchi T , Takagi N , Fujimori K
Published: June 2011

Information on sustained damage to cerebral function and metabolism after cerebral ischemia is useful for prophylaxis and therapeutics of cerebral infarction. The purpose of the present study was to induce sustained damage to brain regions after cerebral ischemia in experimental animals. For this purpose, we examined animal behavior and cerebral energy metabolism following microsphere embolism in rats.

We injected 900 microspheres (48 microns in diameter) into the right internal carotid artery of 110 rats and determined the time course of changes in the rats' behavior and the energy metabolism of the cortex, striatum, and hippocampus of both hemispheres. We injected the same volume of vehicle, without microspheres, into 28 sham-operated rats; there were 14 nonoperated control rats.

Peak increase in lactate content and decrease in adenosine triphosphate and creatine phosphate of these brain regions of the right hemisphere were seen on the first day after microsphere embolism, whereas peak increases in glucose and glycogen contents of these regions were observed on the third day. Most of the metabolic alterations in all these regions continued for up to 28 days after operation, although they recovered toward control levels with time after the operation. The extent and trend of metabolite changes of the right hemisphere after microsphere embolism were similar in the three brain regions. In the left hemisphere, similar metabolic changes were observed, but to a lesser degree. The time course of changes in behavioral scores following microsphere embolism revealed marked stroke-like symptoms on the first day and relatively rapid disappearance of the symptoms with time after embolism.

Microsphere embolism is capable of inducing widespread, sustained damage to energy metabolism of brain regions.
Protective effects of human recombinant superoxide dismutase on transient ischemic injury of CA1 neurons in gerbils.
Authors: Uyama O , Matsuyama T , Michishita H , Nakamura H , Sugita M
Published: June 2011

It has been postulated that oxygen-derived free radicals are produced in significant quantities upon reperfusion of ischemic brain and that the free radicals play a pivotal role in triggering the ischemic neuronal damage causing delayed neuronal death. This study was undertaken to examine the effects of human recombinant superoxide dismutase on the delayed neuronal death of CA1 neurons and on the change in the expression of messenger ribonucleic acid for endogenous copper-zinc superoxide dismutase after transient ischemia.

Human recombinant superoxide dismutase (8 x 10(5) units/kg) or apo-superoxide dismutase was administered intravenously 1 minute before bilateral carotid artery occlusion in gerbils divided among four experimental groups. Endogenous copper-zinc superoxide dismutase messenger ribonucleic acid was analyzed by in situ hybridization histochemistry using a sulfur-35-labeled oligonucleotide probe. Immunohistochemical localizations of administered human recombinant superoxide dismutase were investigated.

All gerbils receiving apo-superoxide dismutase exhibited almost complete destruction of CA1 neurons 7 days after 5 minutes of ischemia. The gerbils treated with human recombinant superoxide dismutase showed mild lesions (p less than 0.01). Discrete localizations were observed for endogenous copper-zinc superoxide dismutase messenger ribonucleic acid. Transient ischemia increased labeling throughout the hippocampus after 30 minutes and 24 hours of reperfusion. This increase was abolished by treatment with human recombinant superoxide dismutase. This phenomenon was confirmed by Northern blot analysis. The interneurons in CA3 and cells in the hilus were mainly stained against administered superoxide dismutase at 5 and 30 minutes, and these reactions had disappeared at 20 hours after the administration.

Our data demonstrate protective effects of human recombinant superoxide dismutase against ischemic neuronal damage and support the hypothesis that the generated free radicals induce a vicious cycle leading to delayed neuronal death.
Stroke incidence rates were unchanged, while fatality rates declined, during 1971-1987 in Göteborg, Sweden.
Authors: Harmsen P , Tsipogianni A , Wilhelmsen L
Published: June 2011

Stroke risk factors have been shown to change with time in several places; simultaneously, stroke incidence rates have increased in some and decreased in other places. In Göteborg, Sweden, cardiovascular epidemiological research has included stroke registration since 1971. From these data on stroke, incidence and fatality rates from a 17-year period are given.

During the period 1971-1987 all cases of stroke occurring in people aged 15-65 years in the city of Göteborg were uniformly recorded, with an estimated case detection rate of 90% or more.

Age-adjusted incidence rates of first-ever stroke by sex did not change during the period. Age-specific rates and rates for individual types of stroke (subarachnoid hemorrhage, intracerebral hemorrhage, and cerebral infarction-unspecified stroke combined) were also largely unchanged. A slight increase in the incidence rate of intracerebral hemorrhage may be due to better detection after computed tomography came into use in 1976. Stroke fatality rates declined through the whole period in both sexes and all age groups, markedly so for intracerebral hemorrhage and subarachnoid hemorrhage.

This conforms with vital statistics for Göteborg and for Sweden of declining stroke mortality during the period. The decline in stroke fatality rates may be related to decreases in smoking habits and blood pressure together with an increase in the percentage of people on antihypertensive treatment among middle-aged men, and to some extent even middle-aged women, reported from the same population. Why stroke incidence rates did not decline concomitantly is unexplained.
Anosognosia in patients with cerebrovascular lesions. A study of causative factors.
Authors: Starkstein S E , Fedoroff J P , Price T R , Leiguarda R , Robinson R G
Published: June 2011

Psychological and biological hypotheses have been proposed to explain anosognosia. We correlated the presence of anosognosia with the presence and severity of psychiatric disturbances, neglect, intellectual impairments, and computed tomographic evidence of lesion size, location, and measurements of brain atrophy.

A series of 80 patients with acute stroke were assessed using a battery of psychiatric and neuropsychological tests and computed tomography.

There were five main findings. First, 27 (28%) of the 96 patients originally screened showed anosognosia. Second, patients with anosognosia had significantly higher frequencies of hemispatial neglect and related phenomena, as well as deficits in recognizing facial emotions and in receptive prosody. Third, depression was equally frequent among patients with and without anosognosia. Fourth, patients with anosognosia had a significantly higher frequency of right hemisphere lesions, primarily involving the temporoparietal junction, thalamus, and basal ganglia. Fifth, patients with anosognosia showed significantly more subcortical brain atrophy, primarily involving the frontal white matter and diencephalic areas.

The present study demonstrates that anosognosia does not "protect" stroke patients from depressive feelings; rather, it represents arousal-attentional disorders after lesions in specific areas of the right hemisphere in nonaphasic patients with preexisting subcortical atrophy.
Protective effect of synaptic inhibition during cerebral ischemia in rats and rabbits.
Authors: Lyden P D , Hedges B
Published: June 2011

Excitatory neurotransmitters appear to cause cell death during ischemia by inducing depolarization, influx of ions, and metabolic failure in the postsynaptic neuron. If this hypothesis is correct, then postsynaptic membrane hyperpolarization and inhibition of metabolism may be protective. Antagonists of the excitotoxic amino acid glutamate protect neurons in culture and in animal models of stroke but appear to cause unacceptable side effects in humans. We propose an alternative strategy of protection using agonists of the inhibitory neurotransmitter gamma-aminobutyric acid.

We caused multifocal cerebral ischemia in rats and rabbits by injecting microspheres into the carotid circulation. We administered saline, muscimol, or MK-801 within 5 minutes of stroke onset. We used a bioassay to measure outcome. In rats, we also used learning to assess cortical function, and we performed detailed quantitative brain morphometry 3 months after infarction.

Using the bioassay, we found that muscimol exerted a protective effect in rats (p less than 0.01). There was a dose-response effect seen in muscimol-treated rabbits. Rats treated with muscimol or MK-801 exhibited significantly better visual-spatial learning compared with saline-treated subjects (p less than 0.001). Hemisphere volume after ischemia was comparable in all groups.

Agonists of gamma-aminobutyric acid and antagonists of glutamate appear to protect brain during ischemia. Since agonists of gamma-aminobutyric acid are known to have fewer side effects in humans, they may prove more useful in the clinical setting as neuroprotective agents.
Tirilazad mesylate does not improve early cerebral metabolic recovery following compression ischemia in dogs.
Authors: Helfaer M A , Kirsch J R , Hurn P D , Blizzard K K , Koehler R C , Traystman R J
Published: June 2011

Tirilazad mesylate (U74006F) has been reported to improve recovery following cerebral ischemia. We conducted a randomized blinded study to determine if the drug would improve immediate metabolic recovery after complete cerebral compression ischemia.

Mongrel dogs were anesthetized with pentobarbital and fentanyl and treated with either vehicle (citrate buffer, n = 8) or tirilazad (1.5 mg/kg i.v. plus 0.18 mg/kg/hr, n = 8). Normothermic complete cerebral compression ischemia was produced for 12 minutes by lateral ventricular fluid infusion to raise intracranial pressure above systolic arterial pressure. Cerebral high-energy phosphate concentrations and intracellular pH were measured by phosphorus magnetic resonance spectroscopy. Cerebral blood flow was measured with radiolabeled microspheres, and oxygen consumption was calculated from sagittal sinus blood samples. Somatosensory evoked potentials were measured throughout the experiment.

During ischemia, both groups demonstrated complete loss of high-energy phosphates and a fall in intracellular pH (vehicle, 5.76 +/- 0.23; tirilazad, 5.79 +/- 0.26; mean +/- SEM). At 180 minutes of reperfusion, there were no differences between groups in recovery of intracellular pH (vehicle, 6.89 +/- 0.07; tirilazad, 6.88 +/- 0.18), phosphocreatine concentration (vehicle, 89 +/- 16%; tirilazad, 94 +/- 24% of baseline value), oxygen consumption (vehicle, 2.6 +/- 0.2 ml/min/100 g; tirilazad, 1.8 +/- 0.5 ml/min/100 g), or somatosensory evoked potential amplitude (vehicle, 11 +/- 6%; tirilazad, 7 +/- 4% of baseline value). Forebrain blood flow fell below baseline levels at 180 minutes of reperfusion in the tirilazad-treated animals but not in the vehicle-treated dogs (vehicle, 28 +/- 4 ml/min/100 g; tirilazad, 18 +/- 5 ml/min/100 g).

We conclude that tirilazad pretreatment does not improve immediate metabolic recovery 3 hours following 12 minutes of normothermic complete ischemia produced by cerebral compression.
Ischemia-induced extracellular release of serotonin plays a role in CA1 neuronal cell death in rats.
Authors: Globus M Y , Wester P , Busto R , Dietrich W D
Published: June 2011

Serotonin, via 5-HT2 receptors, exerts an excitatory effect on CA1 neurons and may play a role in ischemia-induced excitotoxic damage. To evaluate the role of serotonin in ischemia, both neurochemical and histopathological studies were performed.

Neurochemical studies included rats that were subjected to 12.5 or 20 minutes of normothermic ischemia by two-vessel occlusion plus hypotension, and extracellular serotonin levels were measured in the hippocampus (12.5 minutes' ischemia, n = 5) or striatum (20 minutes' ischemia, n = 13) by microdialysis. In the histopathological study the effect of 8 mg/kg ritanserin, a 5-HT2 antagonist, administered continuously from 30 minutes prior to ischemia until 1 hour of recirculation was evaluated in five rats subjected to 10 minutes of ischemia. After 3 days, the numbers of normal-appearing neurons in the CA1 subregions were counted.

Ischemia of 12.5 minutes' duration induced a fourfold increase in serotonin in the hippocampus (mean +/- SEM baseline, 1.86 +/- 0.25 pmol/ml perfusate; during ischemia, 8.14 +/- 0.89 pmol/ml; p < 0.05 by analysis of variance). Twenty minutes of ischemia induced a 25-fold increase in serotonin in the dorsolateral striatum (baseline, 0.98 +/- 0.15 pmol/ml; ischemia, 24.4 +/- 5.93 pmol/ml; p < 0.001). The histopathological study demonstrated severe ischemic damage in all CA1 subregions of nontreated animals (medial, 34 +/- 16 normal-appearing neurons, middle, 52.2 +/- 22.9 neurons; lateral, 56.6 +/- 21.8 neurons). Treatment with ritanserin significantly attenuated ischemic damage (medial, 117.6 +/- 6.5 neurons; middle, 131.4 +/- 4.9 neurons; lateral, 130 +/- 7.5 neurons; p < 0.01 different from nontreated).

Taken together, these results suggest that serotonin plays a detrimental role, mediated by 5-HT2 receptors, in the development of ischemic damage.
Diffusion-weighted imaging studies of cerebral ischemia in gerbils. Potential relevance to energy failure.
Authors: Busza A L , Allen K L , King M D , van Bruggen N , Williams S R , Gadian D G
Published: June 2011

Diffusion-weighted magnetic resonance imaging has been shown to be particularly suited to the study of the acute phase of cerebral ischemia in animal models. The studies reported in this paper were undertaken to determine whether this technique is sensitive to the known ischemic thresholds for cerebral tissue energy failure and disturbance of membrane ion gradients.

Diffusion-weighted images of the gerbil brain were acquired under two sets of experimental conditions: as a function of cerebral blood flow after controlled graded occlusion of the common carotid arteries (partial ischemia), as a function of time following complete bilateral carotid artery occlusion (severe global ischemia), and on deocclusion after 60 minutes of ischemia.

During partial cerebral ischemia, the diffusion-weighted images remained unchanged until the cerebral blood flow was reduced to 15-20 ml.100 g-1.min-1 and below, when image intensity increased as the cerebral blood flow was lowered further. This is similar to the critical flow threshold for maintenance of tissue high-energy metabolites and ion homeostasis. After the onset of severe global cerebral ischemia, diffusion-weighted image intensity increased gradually after a delay of approximately 2.5 minutes, consistent with complete loss of tissue adenosine triphosphate and with the time course of increase in extracellular potassium. This hyperintensity decreased on deocclusion following 60 minutes of ischemia.

The data suggest that diffusion-weighted imaging is sensitive to the disruption of tissue energy metabolism or a consequence of this disruption. This raises the possibility of imaging energy failure noninvasively. In humans, this could have potential in visualizing brain regions where energy metabolism is impaired, particularly during the acute phase following stroke.
Neuroprotective effects of carvedilol, a new antihypertensive agent, in cultured rat cerebellar neurons and in gerbil global brain ischemia.
Authors: Lysko P G , Lysko K A , Yue T L , Webb C L , Gu J L , Feuerstein G
Published: June 2011

Free radical generation mediates part of the ischemic neuronal damage caused by the excitatory amino acid glutamate. Carvedilol, a novel multiple-action antihypertensive agent, has been shown to scavenge free radicals and inhibit lipid peroxidation in swine heart and rat brain homogenates. Therefore, we studied the neuroprotective effect of carvedilol on cultured cerebellar neurons and on CA1 hippocampal neurons of gerbils exposed to brain ischemia.

Neuroprotective mechanisms were studied using an in vitro ischemia model of cultured rat cerebellar granule cell neurons exposed to either glutamate or oxygen free radical-generating systems. Prevention of lipid peroxidation by carvedilol was studied by measuring the formation of thiobarbituric acid-reactive substance. Gerbil CA1 neuron survival was examined by direct neuronal count 7 days after 6 minutes of global ischemia with reperfusion.

Carvedilol protected cultured neurons in a dose-dependent manner against glutamate-mediated excitotoxicity (inhibitory concentration [IC50] = 1.1 microM) as well as against a 20-minute oxidative challenge (IC50 = 5 microM). The IC50 against the oxidative challenge was lowered to 1.3 microM by growing neurons for 24 hours in the presence of carvedilol. At 10 microM carvedilol inhibited lipid peroxidation 50% and 73% (n = 4, p < 0.001) in neurons exposed to two different free radical-generating systems. Neuroprotection of 52% (n = 22, p = 0.009 versus vehicle) of gerbil CA1 hippocampal neurons was achieved by pretreatment and posttreatment with subcutaneous injection of 3 mg/kg carvedilol twice a day for 4 and 3 days, respectively.

Carvedilol provided neuroprotection in both in vitro and in vivo models of neuroinjury, where oxygen radicals are likely to play an important role. Therefore, carvedilol may reduce the risk of cerebral ischemia and stroke by virtue of both its antihypertensive action and its antioxidative properties.
Is cerebral angiography indicated in infective endocarditis?
Authors: van der Meulen J H , Weststrate W , van Gijn J , Habbema J D
Published: June 2011

Patients with infective endocarditis may develop intracranial mycotic aneurysms. Whether these patients should undergo cerebral angiography followed by prophylactic surgery if an aneurysm is detected is an unresolved question.

We estimated the probability of survival 12 weeks after the diagnosis of infective endocarditis on the basis of data available in the literature.

For a 40-year-old female patient with right-sided hemiplegia, the 12-week survival is estimated to be 83.75% without angiography and 83.65% with angiography; the specific mortality of intracranial mycotic aneurysms is relatively small but increases by 40% (from 0.25% to 0.35%) if angiography is performed. The risk of aneurysm rupture in infective endocarditis and the mortality from rupture appear to be the most important factors that affect the analysis.

Cerebral angiography should not be performed routinely in patients with infective endocarditis. Specific subgroups in whom such a policy might be beneficial have not yet been identified.
99mTc-HMPAO-SPECT with acetazolamide challenge to detect hemodynamic compromise in occlusive cerebrovascular disease.
Authors: Knop J , Thie A , Fuchs C , Siepmann G , Zeumer H
Published: June 2011

Insufficiency of collateral supply may lead to low-flow infarcts in severe occlusive cerebrovascular disease. The aim of this study was to evaluate the feasibility of technetium-99m-labeled hexamethylpropyleneamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) to assess hemodynamic compromise in the anterior circulation.

Cerebral blood flow before and after 1 g acetazolamide was analyzed by 99mTc-HMPAO-SPECT in 21 symptomatic patients with documented extracranial obstructions. SPECT findings were correlated with the results of angiography, transcranial Doppler sonography, and computed tomographic scan.

The acetazolamide-induced increase of cerebral blood flow could be reliably monitored by increase of cerebral 99mTc-HMPAO uptake, which varied between 11.4% and 47.6% in the less-affected hemisphere. Increment of hemispheric side-to-side asymmetry of tracer uptake after drug challenge revealed significant restriction of regional vasoreactivity in 11 patients. Agreement in assessing hemodynamic compromise was reached in 81% of patients with ophthalmic artery collaterals on angiography (p < 0.001), in 76% with low-flow infarcts on computed tomographic scan (p < 0.01), and in 91% with markedly reduced flow velocities on transcranial Doppler (p < 0.0001). One patient developed a low-flow infarct in the area predicted by SPECT during follow up.

We conclude that 99mTc-HMPAO-SPECT with acetazolamide challenge is a useful method for assessment of the adequacy of hemispheric collateral pathways in patients with severe occlusive cerebrovascular disease.
Features on initial computed tomography scan of infarcts with a cardiac source of embolism in the NINDS Stroke Data Bank.
Authors: Kittner S J , Sharkness C M , Sloan M A , Price T R , Dambrosia J M , Tuhrim S , Wolf P A , Mohr J P , Hier D B
Published: June 2011

The lack of valid criteria for the clinical diagnosis of cardiogenic embolism is a major problem in both patient care and research. The aim of this study was to identify features on the initial computed tomogram of the brain that discriminate between patient groups with and without a cardiac source of embolism. To gain insight into the neuroradiological features relevant to the diagnosis of cardiac embolic stroke, we studied the initial computed tomogram of the 1,267 patients with ischemic stroke and such a scan in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Data Bank.

We analyzed the initial computed tomographic data from 1,267 patients with ischemic stroke in the NINDS Stroke Data Bank. Based solely on the presence of cardiac sources of embolism, we defined groups with high (n = 244), medium (n = 165), and low (n = 858) risk for cardiogenic embolism and compared the features on the initial computed tomogram among these three groups.

Patients in the high-risk group were significantly more likely (p < 0.001) to have infarcts involving one half lobe or larger or infarcts involving both superficial and deep structures than patients in the medium- or low-risk groups. In contrast, deep small infarcts had a negative association (p = 0.004) with the presence of a cardiac source of embolism. There was no significant trend across risk groups in the percent with hemorrhagic infarction, regardless of whether patients with anticoagulant use at the time of the stroke were excluded.

Although some features of the initial computed tomogram had highly significant associations with the presence of a cardiac source of embolism, the predictive value of these features for an embolic source was low.
Arginine vasopressin V1-antagonist and atrial natriuretic peptide reduce hemorrhagic brain edema in rats.
Authors: Rosenberg G A , Scremin O , Estrada E , Kyner W T
Published: June 2011

Injection of arginine vasopressin into the cerebral ventricles in animals with brain injury increased brain water, whereas injection of atrial natriuretic peptide reduced water content. Therefore, to determine the role of endogenous arginine vasopressin in brain edema, we attempted to inhibit edema from a hemorrhagic lesion with an arginine vasopressin V1 receptor antagonist or atrial natriuretic peptide.

Adult Sprague-Dawley rats with hemorrhages induced by 0.4 IU bacterial collagenase were treated with 75 ng (n = 9) or 8 micrograms (n = 9) of the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)Arg, 3.2 micrograms (n = 4) atrial natriuretic peptide injected intracerebrally, or 5 micrograms/kg per hour (n = 7) atrial natriuretic peptide intraperitoneally. They were compared with control groups injected with 0.4 IU collagenase only. Brain water and electrolytes were measured 24 hours later. Brain uptake of [14C]sucrose was measured 30 minutes after lesions were induced by 0.4 IU collagenase alone (n = 5) or after collagenase injection and 50 micrograms/kg per hour (n = 5) atrial natriuretic peptide injected intravenously.

The arginine vasopressin V1 receptor antagonist and atrial natriuretic peptide significantly (p < 0.05) reduced water and sodium contents in the posterior edematous regions. Brain uptake of [14C]sucrose was significantly reduced by intravenous atrial natriuretic peptide.

Antagonists to arginine vasopressin V1 receptors and atrial natriuretic peptide both significantly reduce hemorrhagic brain edema, and atrial natriuretic peptide appears to protect the blood-brain barrier.
Incidental brain lesions on magnetic resonance imaging and neurobehavioral functions in the apparently healthy elderly.
Authors: Matsubayashi K , Shimada K , Kawamoto A , Ozawa T
Published: June 2011

Controversies exist whether incidental neuroradiological brain lesions in the elderly are associated with depressed neuropsychological function. To address this important issue in a cross-sectional study, we related brain lesions on magnetic resonance imaging to a variety of cognitive and neurobehavioral function tests in an independent, normal elderly population.

We studied 73 independent asymptomatic elderly individuals (mean +/- SD age 70 +/- 6 years) to determine the relations between degree of brain atrophy, location and number of "lacunes," and grade of periventricular hyperintense lesions with a variety of cognitive and neurobehavioral function scores.

We found that severity of neuroradiological changes increased while neuropsychological function scores declined with age. After adjustment for the effect of age, advanced periventricular hyperintensities, but not brain atrophy or patchy "lacunar" lesions, were associated with declines in all neuropsychological functions tested.

We conclude that incidental advanced periventricular diffuse or patchy white matter changes may play a role in the development of cognitive and neurobehavioral impairments in apparently normal elderly persons.
Mechanisms in lacunar infarction.
Authors: Horowitz D R , Tuhrim S , Weinberger J M , Rudolph S H
Published: June 2011

Lacunes are thought to occur in patients with hypertension or diabetes mellitus as a result of small-vessel disease. This study evaluated the importance of other stroke mechanisms in a population of patients with lacunar infarction.

We evaluated 108 consecutive patients with a lacune in the lenticulostriate distribution for other stroke risk factors such as carotid and cardiac disease.

Hypertension was present in 68% of the patients and diabetes mellitus in 37%; both occurred in 28% and neither occurred in 23%. Noninvasive carotid studies identified atherosclerotic plaque as a possible embolic source in 23%. By previously established criteria, 18% were at high risk for cardioembolism. Of those with hypertension or diabetes mellitus, 36% were at risk for a carotid or cardiac embolus. Of those without hypertension or diabetes mellitus, 32% had a possible carotid or cardiac etiology.

The high incidence of carotid and cardiac disease in those with and without hypertension or diabetes mellitus suggests the importance of other stroke mechanisms in this population. Patients with lacunar infarction should therefore be evaluated for other causes of stroke that may be treatable.
Effects of public and professional education on reducing the delay in presentation and referral of stroke patients.
Authors: Alberts M J , Perry A , Dawson D V , Bertels C
Published: June 2011

Several emerging stroke therapies require patients to be treated within several hours of symptom onset. Past studies have documented a significant delay between symptom onset and hospital presentation. As part of an experimental treatment study using tissue-type plasminogen activator, we began a multifaceted program of public and professional education to reduce the delay in presentation and referral of acute stroke patients.

The educational efforts focused on improving the recognition of stroke symptoms, the study enrollment criteria, and the need for rapid treatment of stroke patients. This program included 1) interviews on television and radio, 2) newspaper articles, 3) lectures to local and regional primary care and emergency department physicians, 4) mailings to several thousand local physicians, 5) having neurologists on-call for referrals 24 hrs/day, and 6) use of the Duke Life-Flight helicopter.

Since starting our program, 139 of 159 (86%) patients with cerebral infarction presented primarily to our were referred to our facility within 24 hours of symptom onset, compared with 70 of 187 (37%) before our educational efforts (p less than 0.00001). No significant change was seen in patients with intracerebral hemorrhage (23 of 30 +AD77%+BD within 24 hours after program, compared with 25 of 40 +AD63%+BD before educational efforts; p = 0.30).

These findings suggest that educational efforts aimed at the public and health professionals may increase recognition of stroke symptoms and reduce the delay in presentation and referral of stroke patients.
Ultrasonic evaluation of the site of carotid axis occlusion in patients with acute cardioembolic stroke.
Authors: Yasaka M , Omae T , Tsuchiya T , Yamaguchi T
Published: June 2011

We performed the present study to determine whether the site of cardioembolic occlusion in the carotid axis could be identified by end-diastolic velocity measurements of the common carotid arteries.

Using duplex carotid ultrasonography, we measured the flow velocity in the common carotid arteries and calculated the side-to-side ratios of the end-diastolic velocity (ED ratio; the end-diastolic velocity of the nonaffected side divided by that of the affected side) in 46 patients with acute cardioembolic stroke. The velocity on the faster side was divided by the slower velocity to obtain the normal values of ED ratio in 30 controls. The ED ratios were compared with the angiographic findings, in which unilateral intracranial internal carotid artery occlusion was present in 20 patients (IC group), occlusion of the horizontal segment of the middle cerebral artery was present in 16 patients (M1 group), and branch occlusion of the middle cerebral artery was present in 10 patients (MBr group). The ED ratios of the control group were less than 1.3; those of the MBr group generally less than 1.3; the IC group greater than 4.0, except in two patients with severe cerebral edema; and those of the M1 group between 1.3 and 4.0. Therefore, the IC group was easily distinguished from the other groups by an ED ratio greater than or equal to 4.0, with an accuracy of 97%, and the M1 group by an ED ratio greater than or equal to 1.3 and less than 4.0, with an accuracy of 93%.

We found the ED ratio useful to identify internal carotid artery and middle cerebral artery occlusion in patients with cardioembolic stroke unless severe cerebral edema was present.
Computed tomography in prognostic stroke evaluation.
Authors: Rasmussen D , Køhler O , Worm-Petersen S , Blegvad N , Jacobsen H L , Bergmann I , Egeblad M , Friis M , Nielsen N T
Published: June 2011

Computed tomography is now routinely used in many hospitals to investigate cerebrovascular disease. The purpose of our prospective study was to determine whether cranial computed tomography in connection with neurological assessment was useful in prognostic evaluation of survival after acute stroke.

Two-hundred forty-five consecutive stroke patients were included in the project during a 1-year period. Each had a detailed neurological assessment 24-72 hours after stroke onset and underwent cranial computed tomography without intravenous contrast injection within the first week after admission. The lesions were divided according to neuroanatomic regions. In the statistical analyses we used a multiple logistic regression model with survival/death as the binary variable.

Computed tomography showed 76% of the patients had infarcts, 11% had hemorrhages, and 13% had no acute lesion. Forty-three patients had more than one acute lesion, and 57 had one or more old infarctions. The temporal, parietal, and frontal regions and the basal ganglia were most often affected.

We conclude that age, level of consciousness, and involvement of the temporal lobe on computed tomography were factors of prognostic significance regarding survival in the acute phase.
Release of superoxide dismutase into cerebrospinal fluid as a marker of brain lesion in acute cerebral infarction.
Authors: Strand T , Marklund S L
Published: June 2011

Evaluation of biochemical patterns in cerebrospinal fluid may add diagnostic and prognostic information. We tested to determine whether the concentration of superoxide dismutase in cerebrospinal fluid is a marker of brain tissue damage in acute ischemic stroke.

We investigated 36 acute ischemic stroke patients for cerebrospinal fluid activity of the enzyme superoxide dismutase on two occasions shortly after symptom onset (average, day 1 and day 4).

In 75% of the patients, the first of two lumbar punctures revealed the maximal superoxide dismutase value. The amount in the cerebrospinal fluid was significantly correlated with the size of infarction on computed tomographic scan (p less than 0.001 by analysis of variance) and to functional impairment and stroke-related mortality during initial hospital stay (p less than 0.002). The correlation of initial superoxide dismutase concentration with the need for long-term institutional care and mortality at 3 months after the stroke was also significant (p less than 0.03).

We conclude that superoxide dismutase in cerebrospinal fluid is a marker of an acute brain lesion and has some value as a prognostic predictor. This small enzyme leaks rapidly from ischemically injured cells.
A rat model of severe neonatal hypoxic-ischemic brain injury.
Authors: Schwartz P H , Massarweh W F , Vinters H V , Wasterlain C G
Published: June 2011

Perinatal hypoxic-ischemic brain injury is a common problem with severe neurological sequelae. In this report we describe in detail a simple model of hypoxia-ischemia in the neonatal rat that gives rise to severe neocortical infarction and to selective hippocampal neuronal necrosis.

Seven-day-old Simonsen Wistar rat pups underwent bilateral carotid artery ligation under methoxyflurane anesthesia and, after a 4 to 6-hour recovery, were exposed to 60 minutes of hypoxia (6.5% O2); they were perfusion-fixed 3 days later for histological study. Brain temperature was monitored throughout this treatment.

We found that 64 +/- 3% of neocortex above the rhinal sulcus was infarcted; this infarction was evenly distributed through the cerebral hemispheres. In the hippocampus, neuronal necrosis was selective for the internal (hilar) layers of granule cells of the dentate gyrus, with relative sparing of CA1 pyramidal cells. In addition, brain temperature was tightly controlled throughout the experimental manipulations.

The present model is easy and sensitive and provides an infarct of sufficient severity and homogeneity to make it well suited for pharmacological and biochemical studies directed toward therapeutic amelioration and mechanisms of hypoxic-ischemic brain damage, respectively. In addition, the pattern of damage in the hippocampus is quite different from that seen in the adult brain, which should be helpful in studying the ontogeny of selective vulnerability.
Effects of carbon dioxide inhalation on cerebral blood flow and oxygen tissue level in spontaneously hypertensive rabbits.
Authors: Hegedüs K , Fekete I , Molnár L
Published: June 2011

Because previous studies have yielded conflicting results, this study was designed to investigate the efficiency of cerebrovascular reactivity to carbon dioxide in hypertension associated with moderate diffuse cerebral ischemic lesions.

The effects of carbon dioxide inhalation on mean arterial blood pressure, heart and respiration rates, cerebral cortical blood flow, polarographically detected oxygen currents (oxygen availability), and cerebral electrical activity were compared in 14 spontaneously hypertensive and 16 normotensive rabbits anesthetized with urethane and alpha-chloralose. Blood flow was measured with the hydrogen clearance and thermal clearance methods.

In the resting state the frequency of electrical activity shifted to slower components, the levels of oxygen availability and cerebral blood flow were lower (p less than 0.01), and the ratio of the two latter parameters was greater (p less than 0.01) in hypertensive rabbits than in normotensive animals. Carbon dioxide inhalation induced more marked increases in cerebral blood flow, respiration rate, and oxygen availability in hypertensive (p less than 0.01) than in normotensive (p less than 0.05) rabbits. The ratio of oxygen availability to cerebral blood flow decreased (p less than 0.01) in the former and did not change significantly in the latter group. The carbon dioxide-induced rise in blood flow was also slower and more protracted in hypertensive rabbits (p less than 0.01). Histological investigation revealed groups of neurons with ischemic changes in the cortex of the hypertensive rabbits.

We suggest that in hypertensive rabbits the mild multiple ischemic lesions are the basis of functional disturbances, including reduced resting cerebral blood flow, greater oxygen tissue level, slower response to carbon dioxide, and greater vasodilatory capacity.
Evaluation of long-term outcome and safety after hemodilution therapy in acute ischemic stroke.
Authors: Strand T
Published: June 2011

In a previous single-center, randomized controlled trial including 102 patients treated in a stroke unit, we showed that rapid, modest hemodilution improved short-term clinical outcome in ischemic stroke patients. I now evaluate the long-term outcome and potential risks of this combined venesection/dextran 40 therapy in the same 52 treated and 50 control patients.

Mortality, need for institutional care, and recurrent strokes were registered during 1 year following inclusion in the trial, and a final evaluation of functional outcome was performed at 12 months after the stroke. Cerebrospinal fluid was analyzed for protein content and hemorrhagic admixture at two occasions during the acute phase.

Thirty-six hemodiluted and 30 control patients survived the first year following the stroke (difference not significant). One year after the stroke, persistent neurological deficits were less frequent among the hemodiluted patients and a larger proportion of hemodiluted survivors was independent in walking (92% versus 73%, p less than 0.05). Two hemodiluted patients (6%) and nine control patients (30%) were totally dependent in the activities of daily living (p less than 0.05). Three hemodiluted patients (8%) and eight control patients (27%) remained hospitalized 1 year after the stroke (p less than 0.05). With the possible exception of patients with a medical history of congestive heart failure, subset analyses revealed a tendency toward improved outcome for hemodiluted patients in all clinically important subgroups compared with the controls. When analyzing cerebrospinal fluid, signs of blood-brain barrier breakdown and hemorrhagic admixture to the cerebrospinal fluid during the acute phase were less frequent in the hemodiluted subjects.

These results suggest that, when applied in a stroke unit, the combination of venesection and dextran 40 administration is a clinically safe, therapeutic regimen in the treatment of acute cerebral infarction that improves long-term clinical outcome.
Stroke with negative brain magnetic resonance imaging.
Authors: Alberts M J , Faulstich M E , Gray L
Published: June 2011

Magnetic resonance imaging (MRI) of the brain is replacing computed tomography in the diagnostic evaluation of acute ischemic strokes. Past studies have suggested that MRI may not visualize all acute strokes, but few clinical details were included. To better understand the clinical characteristics of strokes not detected by MRI, we collected and reviewed case histories of several patients with acute stroke who had negative MRI scans.

Patients with a clinical diagnosis of stroke and negative brain MRI scans were ascertained from hospital records dating from 1989 to mid-1991. Patients with transient ischemic attacks, postictal paralysis, functional examinations, central nervous system infections, other nonstroke diagnoses, or equivocal findings were excluded. The MRI scans were performed with a GE Signa 1.5-T magnet in an axial plane (spin-echo repetition time/echo time: 500 msec/20 msec; 2,500 msec, 30 msec/80 msec). One patient received contrast material.

We identified seven patients with clinically diagnosed ischemic stroke and negative brain MRI scan. Six of seven patients were scanned within 7 days of symptom onset and two patients within 24 hours. One patient was scanned 3 months after symptom onset. The strokes not detected by MRI were clinically localized to the cortex (n = 3), brain stem (n = 3), and subcortical/lacunar area (n = 1). One patient underwent two MRI scans, one with gadolinium.

These cases, while selected, illustrate some potential limitations of MRI for diagnosing stroke.