bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcitonin gene-related peptide reduces brain injury in a rat model of focal cerebral ischemia.
Authors: Holland J P , Sydserff S G , Taylor W A , Bell B A
Published: June 2011

Calcitonin gene-related peptide is an endogenous vasodilating neuropeptide with a dense concentration in the trigeminocerebrovascular system. It is hypothesized that depletion of this peptide contributes to delayed cerebral ischemia after subarachnoid hemorrhage and that an exogenous supply of calcitonin gene-related peptide will augment ischemic cerebral blood flow and reduce neuronal injury.

In this study we have investigated the effect of an intravenous infusion of calcitonin gene-related peptide (100 ng/kg per minute), started 1 hour before and continued throughout 4 hours of focal cerebral ischemia, on cerebral blood flow and the volume of brain injury in a rat model of middle cerebral artery occlusion.

Calcitonin gene-related peptide produces a significant improvement in ischemic cerebral blood flow (32 +/- 2 compared with 13 +/- 2 mL/100 g per minute in the controls; t = 6.92, P < .0001) with a concomitant reduction in the volume of ischemic brain injury (102 +/- 22 compared with 234 +/- 19 mm3; t = 4.47, P < .001).

These findings lend support for the potential use of this peptide in the prophylactic treatment of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.
Dihydropyridine ligand binding decreases earlier in adolescent than in infant swine after global cerebral ischemia.
Authors: Hoehner P J , Kirsch J R , Helfaer M A , Ganunis T F , Murphy M T , Traystman R J
Published: June 2011

Voltage-dependent calcium channels (VDCCs) are thought to play a major role in the alteration of calcium homeostasis during ischemia. Tissue functional state as well as responsiveness to therapy with calcium channel blockers may be a function of regional changes in the density of VDCCs. This study determined whether VDCCs are altered by global ischemia in infant and adolescent swine.

We employed the radioligand 3HPN200-110 to quantify the binding characteristics of VDCCs in cerebral cortex, caudate, and hippocampus by equilibrium binding analysis. Adolescent and infant pigs underwent 3, 5, 10, and 20 minutes of global cerebral ischemia without reperfusion by ligation of the brachiocephalic and left subclavian arteries combined with hypotension to a mean arterial blood pressure of 50 mm Hg. Brain cortex, hippocampus, and caudate samples were taken during ischemia and frozen immediately in liquid nitrogen, and crude synaptosomal membranes were isolated by differential centrifugation/filtration. 3HPN200-110 equilibrium binding assays were performed in the presence or absence of 1.0 mumol/L unlabeled nitrendipine to determine total and nonspecific binding.

Infant cortex maximal binding (Bmax) increased to 176% of control after 5 minutes of global cerebral ischemia and remained significantly elevated (172% of control) after 10 minutes before falling to near control levels by 20 minutes. Adolescent cortex Bmax increased to 157% of control levels after 5 minutes but did not remain elevated, falling to 131% of control by 10 minutes and near control by 20 minutes. Infant caudate and hippocampus binding were significantly elevated after 10 (124% and 149% of control, respectively) and 20 (115% and 120% of control, respectively) minutes of ischemia. Adolescent caudate and hippocampus binding was either not significantly different from control levels (hippocampus at 10 minutes) or less than control after 10 and 20 minutes of global cerebral ischemia. The decrease in binding following the initial upregulation, which appeared earlier in the adolescent than the infant pigs, may indicate decreased tolerance to ischemia in the adolescent.

The binding of 3HPN200-110 in brain is altered during 20 minutes of global cerebral ischemia, and these changes are region- and age-dependent.
Dipyridamole increases oxygen-glucose deprivation-induced injury in cortical cell culture.
Authors: Lobner D , Choi D W
Published: June 2011

Adenosine transport inhibitors attenuate ischemic central neuronal damage in vivo, but the locus of this protective action is presently unknown. To help address the question of whether adenosine transport inhibitors have a protective effect directly on brain parenchyma, we tested the effect of the adenosine transport inhibitor dipyridamole on neuronal loss induced by oxygen-glucose deprivation in vitro.

Murine cortical cultures were exposed to combined oxygen and glucose deprivation, N-methyl-D-aspartate, or kainate. The extracellular concentrations of glutamate and adenosine were measured by high-performance liquid chromatography; neuronal cell death was assessed by morphological examination and measurement of lactate dehydrogenase release.

Cultures exposed to oxygen-glucose deprivation for 30 to 75 minutes exhibited an insult-dependent increase in extracellular adenosine, followed shortly by an increase in extracellular glutamate and 24 hours later by neuronal death. Addition of the A1 receptor antagonist 8-cyclopentyltheophylline during oxygen-glucose deprivation enhanced both glutamate release and neuronal damage. Addition of 10 mumol/L dipyridamole decreased extracellular adenosine and also enhanced extracellular glutamate and neuronal death. In contrast, dipyridamole increased the levels of extracellular adenosine stimulated by N-methyl-D-aspartate or kainate.

These results are consistent with the idea that endogenous adenosine has a neuroprotective effect directly on cortical cells exposed to oxygen-glucose deprivation. However, inhibition of adenosine transport with dipyridamole was surprisingly not an effective strategy for enhancing this protective effect. The beneficial effects of adenosine transport inhibitors observed in vivo may be mediated indirectly--for example, by effects on the vasculature.
Urgent therapy for acute stroke. Effects of a stroke trial on untreated patients.
Authors: Barsan W G , Brott T G , Broderick J P , Haley E C , Levy D E , Marler J R
Published: June 2011

As part of the recruitment efforts for the National Institutes of Health Tissue Plasminogen Activator Pilot Study, public education and awareness campaigns were conducted to encourage early hospital arrival. We evaluated the change in arrival times during the course of the study for all stroke patients, including those who were not entered into study.

Data were gathered on all patients presenting within 24 hours of stroke onset to all of the study hospitals. Coincident with the start of the study, educational and promotional programs, which stressed signs and symptoms of stroke and the need to call 911, were presented to physicians, paramedical personnel, and the public. The study was divided into four quartiles to analyze differences in time to hospital arrival and use of 911.

Of 2099 patients screened, time data were available on 1116. During the course of the study, the mean time from symptom onset to hospital arrival declined significantly (3.2 hours versus 1.5 hours). Patients arrived for treatment sooner at community hospitals than at university/teaching hospitals. The use of 911 increased from 39% in the first quartile of the study to 60% in the fourth quartile. This was a consistent finding in all study sites. Increased use of 911 was seen almost exclusively in patients with nonhemorrhagic stroke.

Times from stroke onset to hospital arrival decreased significantly during the course of the National Institutes of Health Tissue Plasminogen Activator Pilot Study. Significantly increased use of 911 was the likely major explanation for the shortened arrival times. The decrease in arrival times may be a consequence of the public and professional education programs conducted at all study sites.
Diagnosis of moyamoya disease with magnetic resonance angiography.
Authors: Houkin K , Aoki T , Takahashi A , Abe H
Published: June 2011

Present criteria for the diagnosis of moyamoya disease emphasize the use of conventional cerebral angiography as an indispensable requirement. However, magnetic resonance angiography (MRA) is fast becoming a reliable diagnostic modality for occlusive cerebrovascular diseases. The purpose of this study is to assess the accuracy of MRA compared with conventional angiography.

Thirty-nine patients (23 children and 16 adults) with moyamoya disease confirmed by conventional angiography (78 side views) were examined with MRA (three-dimensional time-of-flight technique with a 256 x 256 or 256 x 512 matrix). T1- and T2-weighted MR images were also taken.

The stenotic or occlusive change at the carotid fork was clearly revealed by MRA, which correlated well with conventional angiography (83% good correlation, 17% overestimation). Apparent moyamoya vessels were clearly shown as a signal void on the MR image and fine unusual vessels on MRA, particularly in children with moyamoya disease (82%). However, small moyamoya vessels were poorly shown on both MR images and MRA, particularly in adults (63%).

MRA can be an alternative to conventional angiography in typical moyamoya disease cases (the bilateral type of moyamoya disease in children). However, in the early or the end stages of moyamoya disease, diagnosis by means of MRA should be carefully evaluated.
Prognostic value of transcranial magnetic stimulation in acute stroke.
Authors: Araç N , Sağduyu A , Binai S , Ertekin C
Published: June 2011

The aim of this study is to evaluate the role of motor-evoked potentials (MEPs) in predicting functional recovery of hemiparesis and hemiplegia in acute stroke patients.

Twenty-seven acute stroke patients were evaluated clinically and electrophysiologically within the first week and 3 to 6 months after the event. Clinical assessment included a quantitative evaluation of motor ability and activities of daily living. MEPs were recorded from the abductor pollicis brevis and tibialis anterior muscles bilaterally. Correlations between clinical parameters and MEPs were assessed.

In the acute period, no MEP could be detected in 17 of 27 patients. In these 17 patients, the clinical scores were worse than in the patients whose MEPs could be elicited. However, in the follow-up period (3 to 6 months), no significant differences in motor function were observed between the two groups.

In the acute phase of stroke, neurophysiological parameters were correlated with the clinical findings, but MEPs had no value in predicting the outcome of hemiparesis and hemiplegia.
Nitric oxide regulates cerebral arteriolar tone in rats.
Authors: Kimura M , Dietrich H H , Dacey R G
Published: June 2011

Although cerebral penetrating arterioles are main regulators of the brain microcirculation, little is known about the effect of endothelium-derived relaxation factor on these vessels. This study examined the effects of nitric oxide synthase inhibitors on the spontaneous tone of isolated rat cerebral arterioles.

Intraparenchymal penetrating arterioles (53 to 102 microns in passive diameter) isolated from Sprague-Dawley rats were cannulated with glass pipettes and subjected to 60 mm Hg of intraluminal pressure. The diameter response to intraluminal and extraluminal treatments was observed with an inverted microscope.

Extraluminal application of Nw-nitro-L-arginine (10(-5) mol/L) contracted the arterioles to 63.9 +/- 2.8% (P < .05) of the control diameter. This contracting effect was stereospecific and easily reversed by L-arginine dose dependently (10(-3), 10(-2) mol/L) but not by D-arginine. Intraluminally applied Nw-nitro-L-arginine also induced a similar degree of contraction. Another nitric oxide synthase inhibitor, NG-monomethyl L-arginine (10(-5), 10(-4) mol/L), applied extraluminally induced a dose-dependent contraction to 77.5 +/- 6.6% and 68.6 +/- 5.4% of the control (P < .05), which was also reversed by L-arginine. L-Arginine alone did not significantly affect vessel diameter, however. Treatment with indomethacin, a cyclooxygenase inhibitor, dilated the vessel to 115.2 +/- 7% (P < .05) but did not change the constricting effect of Nw-nitro-L-arginine.

Nw-Nitro-L-arginine and NG-monomethyl L-arginine produce substantial contraction in isolated brain arterioles, suggesting that nitric oxide of brain arterioles is continuously produced within the vessel wall. The dilatory effect of indomethacin appears to be independent of the vasoconstriction induced by nitric oxide synthase inhibitor. In these vessels, the effect of nitric oxide synthase inhibitors is not mediated by an indomethacin-sensitive mechanism. A balance probably exists between factors tending to constrict these arterioles and the elaboration of nitric oxide from endothelial cells, which tends to dilate them. The production of nitric oxide from isolated vessels indicates that parenchymal and vessel wall sources of nitric oxide are probably important in brain microcirculatory regulation.
Stability of thrombosis induced by electrocoagulation of rat middle cerebral artery.
Authors: el-Sabban F , Reid K H , Zhang Y P , Edmonds H L
Published: June 2011

Although it is often assumed in experimental stroke studies that cautery-induced occlusion is permanent, surgeons commonly expect cauterized vessels to recanalize spontaneously. We used the rat middle cerebral artery to determine if electrocoagulation would produce a permanent occlusion in this preparation.

A standard bipolar coagulator, calibrated to determine actual power output, was adjusted to induce platelet aggregation in the middle cerebral artery of anesthetized Sprague-Dawley rats without inducing bleeding through the arterial wall. A reliable temporary thrombosis was induced by a Malis Bipolar Coagulator set to deliver 10 bursts of 1.5 seconds each at a rate of 24 min-1 and a power setting of 3 W. This thrombus was responsive to the antithrombotic agent flunarizine. An apparently permanent occlusion was produced by 30 bursts at 3 W followed by 20 bursts at 5 W. To our surprise, seven of seven such occlusions recanalized spontaneously within 4 hours.

The electrocoagulation process commonly used in experimental stroke studies may produce only a temporary occlusion of the rat middle cerebral artery.
Sjögren's syndrome presenting as ischemic stroke.
Authors: Bragoni M , Di Piero V , Priori R , Valesini G , Lenzi G L
Published: June 2011

We describe a young woman who presented with minor stroke as a first clinical symptom of Sjögren's syndrome (SS) in the absence of well-known risk factors for cerebrovascular disease.

The medical history included recurrent miscarriages and sun rashes, which directed the diagnosis toward immunologic disorders such as systemic lupus erythematosus and antiphospholipid antibody syndrome, which are often associated with stroke. Only complete laboratory testing, including SSB antibody studies, and ophthalmologic and salivary gland evaluation revealed the correct diagnosis.

Sjögren's syndrome should be considered among the causes of stroke, especially in a young female patient.
Use of Medicare claims data to estimate national trends in stroke incidence, 1985-1991.
Authors: May D S , Kittner S J
Published: June 2011

Although stroke mortality has been declining in the United States for decades, recent trends in stroke incidence based on national data have not been described. We used Medicare hospitalization data to estimate national trends in the incidence of stroke among Americans aged 70 years or older, and we provide evidence of the validity of the estimate.

We defined stroke as a principal diagnosis with International Classification of Diseases, 9th Revision, Clinical Modification codes 430 to 434 or 436 to 437. We excluded many recurrent cases from the analysis by eliminating persons hospitalized for stroke during the 5 years preceding the index stroke. We calculated annual adjusted incidence rates and examined trends graphically. We investigated the effect of different exclusion periods, trends in in-hospital mortality of stroke patients, and trends in out-of-hospital stroke mortality. We examined trends in relation to sex, race, and age.

The estimated age- and sex-adjusted stroke incidence declined 9.5% from 1985 to 1989, then increased 3.3% to 1991. The pattern did not vary with the length of the exclusion period or when all listed diagnosis rather than principal diagnoses were used to identify stroke cases. Incidence trends resembled the overall trend for both men and women, for 5-year age groups, and for whites; the trend did not change for blacks.

Stroke incidence declined steadily from 1985 to 1989 and then increased slightly to 1991. Several postulated potential sources of bias were investigated and found to be unlikely to account for the incidence decline, although some may have contributed to the subsequent incidence increase.
Body mass index and thromboembolic stroke in nonsmoking men in older middle age. The Honolulu Heart Program.
Authors: Abbott R D , Behrens G R , Sharp D S , Rodriguez B L , Burchfiel C M , Ross G W , Yano K , Curb J D
Published: June 2011

While evidence suggests that obesity has an independent relation to coronary artery disease, similar findings for stroke have not been established. The purpose of this study was to examine the relation between body mass index and the risk of thromboembolic stroke independently of other risk factors.

Since 1965, the Honolulu Heart Program has followed a cohort of men in a prospective study of cardiovascular disease. This article examines the relationship between the baseline measurement of body mass index and the risk of thromboembolic stroke in 1163 nonsmoking men in older middle age (55 to 68 years). Men who had an elevated risk of stroke due to hypertension, diabetes, and other risk factors were excluded from the analysis.

After 22 years of follow-up, the rate of stroke increased significantly with increasing levels of body mass (P < .01). In the bottom tertile of the body mass index, the rate of thromboembolic stroke was 28.7 per 1000 (11/383). In the middle tertile, the rate was increased by 40% to 40.7 per 1000 (16/393), and in the top tertile, the rate of thromboembolic stroke was 55.4 per 1000 (21/387), a twofold excess compared with the bottom tertile. After adjustment for age and the residual effects of confounding risk factors, including systolic blood pressure and serum glucose, the estimated relative risk of stroke for the average body mass index in the top tertile (26.6 kg/m2) compared with that in the bottom tertile (20.3 kg/m2) was 2.1 (95% confidence interval, 1.1 to 4.1). These findings were not affected by coronary events that occurred in the course of follow-up, nor did they appear to be influenced by deaths from other causes.

We conclude that elevated body mass is associated with an increased risk of thromboembolic stroke in nonsmoking men in older middle age who are free of commonly observed conditions related to cardiovascular disease.
Silent brain infarcts in 755 consecutive patients with a first-ever supratentorial ischemic stroke. Relationship with index-stroke subtype, vascular risk factors, and mortality.
Authors: Boon A , Lodder J , Heuts-van Raak L , Kessels F
Published: June 2011

We wanted to establish independent associations of various clinical variables, computed tomographic (CT) scan features, presenting stroke subtypes, and outcome with the presence of silent infarcts on CT.

We studied 755 consecutive patients in a prospective registration of patients with first-ever supratentorial atherothrombotic, cardioembolic, or lacunar stroke or stroke of undetermined cause by multiple logistic regression analysis.

Two hundred six patients (27%) with a first symptomatic territorial or small deep ischemic stroke had one or more silent infarcts on CT. Of all silent lesions, 169 (82%) were small and deep. Silent infarcts were significantly more strongly associated with a lacunar than atherothrombotic (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.02 to 2.47; P = .039) or cardioembolic (OR, 1.89; 95% CI, 1.2 to 2.99; P = .005) index stroke. Silent territorial lesions were more strongly associated with cardioembolic than with lacunar stroke but not with atherothrombotic stroke. In this respect, no differences were found between the atherothrombotic and undetermined-cause group. Advanced age and hypertension were the only risk factors that were significantly associated with silent infarcts (OR, 1.76; 95% CI, 1.14 to 2.71; P = .011; and OR, 1.58; 95% CI, 1.13 to 2.21; P = .007; respectively), mainly because of a strong independent association of these risk factors with silent small deep infarcts (OR, 1.75; 95% CI, 1.10 to 2.79; P = .018; and OR, 1.57; 95% CI, 1.09 to 2.24; P = .014; respectively). A cardioembolic source or atrial fibrillation in specific was not independently associated with any type or number of silent infarcts. Significant carotid stenosis (diameter reduction > 50%) was not significantly associated with any type of silent lesion. Initial severe handicap (Rankin Scale score > 3), 30-day case fatality rate, and 1-year mortality were not affected by the presence of silent infarcts.

The strong association of silent small deep lesions with first symptomatic small deep infarcts suggests a common underlying mechanism (presumably small-vessel vasculopathy), whereas cardiogenic embolism and large-vessel thromboembolism are the most likely causes in both silent and first symptomatic territorial infarcts. Single or multiple silent infarcts do not predict a cardioembolic stroke mechanism in first symptomatic supratentorial brain infarcts. As silent infarcts do not predict the cause of carotid embolic stroke in first symptomatic brain infarcts, their presence should not influence the decision on carotid surgery. Silent infarcts do not affect the degree of initial handicap, 30-day case fatality, or 1-year mortality. The significance of silent infarcts for predicting possible future cognitive decline and risk of recurrent stroke deserves further study.
Detection of reverse flow by duplex ultrasonography in orthostatic hypotension.
Authors: Yonehara T , Ando Y , Kimura K , Uchino M , Ando M
Published: June 2011

The aim of this study is to elucidate the effect of orthostatic hypotension on changes in cerebral blood flow.

Blood flow velocities of both the common carotid artery and vertebral artery were measured using duplex ultrasonography in 12 patients: 6 with familial amyloidotic polyneuropathy, 3 with Shy-Drager syndrome, 2 with pandysautonomia, and 1 with senile orthostatic hypotension. Simultaneously, peripheral blood flow was also evaluated by laser-Doppler flowmetry.

The patients showing dizziness or syncope when tilted to a 70 degrees upright position exhibited characteristic reverse flow at the end-diastolic phase on the Doppler flow image of both the common carotid and vertebral arteries, which was effectively treated by infusion of 2.5 micrograms/min norepinephrine for 10 minutes. This end-diastolic reverse flow was not seen in any patients who did not have dizziness or syncope. After subjects were tilted from a supine to a 70 degrees upright position, decrease in the peripheral blood flow of the patients with orthostatic hypotension remained unchanged for at least 5 minutes, whereas that of control subjects was recovered within 2 minutes. However, no significant difference between the patients with and without clinical symptoms was observed.

These results suggest that detection of this specific echographic pattern may be quantitatively useful in examination of clinical symptoms accompanying orthostatic hypotension and that duplex ultrasonography may be a helpful tool to evaluate the effect of drugs used for controlling these clinical signs.
Increased proportion of docosahexanoic acid and high lipid peroxidation capacity in erythrocytes of stroke patients.
Authors: Imre S G , Fekete I , Farkas T
Published: June 2011

Intracellular accumulation of lipid peroxides that derive from the autoxidation of membrane polyunsaturated fatty acids reduces the deformability of erythrocytes contributing to the hemorheological disturbances observed in acute cerebral ischemia. The present study deals with the biochemical background of increased lipid peroxidation capacity in the erythrocytes of stroke patients.

A complete clinical and laboratory assessment was made of 24 men and 18 women (aged 50 to 78 years; 64.5 +/- 13.9 years, mean +/- SD) who had an ischemic hemispheric lesion of the brain. Lipid peroxide content, lipid peroxidation capacity, superoxide dismutase activity, and fatty acid composition of erythrocytes were compared in stroke patients and 22 healthy subjects matched for age. The lipid peroxide content of the erythrocytes was estimated before and after the autoxidative test; the results were expressed as nanomoles of malondialdehyde per gram of hemoglobin. The increase of the lipid peroxide content in the erythrocytes during the autoxidative test measures the lipid peroxidation capacity.

In comparison with healthy subjects (1.45 +/- 0.30 nmol MDA/g Hb per 24 hours), the lipid peroxidation capacity was found to be significantly higher (4.18 +/- 0.41 nmol MDA/g Hb per 24 hours) (P < .01) in the erythrocytes of stroke patients. The stroke patients could be divided into two groups on the basis of lipid peroxidation capacity of their erythrocytes. Twenty patients had erythrocytes with high lipid peroxidation (< 4 nmol MDA/g Hb per 24 hours), and 22 patients had very high lipid peroxidation capacity (> 4 nmol MDA/g Hb per 24 hours). There was no significant difference in superoxide dismutase activity in the erythrocytes of patients compared with healthy subjects. Before the autoxidative test was conducted, the fatty acid composition in the erythrocytes of stroke patients with very high lipid peroxidation capacity was measured and found to be generally normal; only the proportion of docosahexanoic acid (22:6 n-3) was markedly (P < .01) increased.

The results suggest that the erythrocytes of ischemic stroke patients with very high lipid peroxidation capacity displaying an abnormal fatty acid composition are much more vulnerable to lipid peroxidation. The increased proportion of docosahexanoic acid and the high lipid peroxidation capacity of erythrocytes play a pathogenetic role and explain the hemorheological disturbances observed in the microcirculation of stroke patients.
A rapid, reliable, and valid method for measuring infarct and brain compartment volumes from computed tomographic scans.
Authors: Lyden P D , Zweifler R , Mahdavi Z , Lonzo L
Published: June 2011

Clinical stroke trials require objective and reproducible end point variables. Morphometry of cerebral structures, including infarct volume, provides numerical measures that represent the amount of tissue damaged and potentially salvaged by therapy. However, morphometry may be time-consuming and labor-intensive, and it requires standardization across multiple centers, which may be difficult to achieve in large multicenter trials. We developed a brain morphometry method that is unbiased, rapid, reliable, and based on well-accepted stereological techniques. We now extend this method to analysis of routine computed tomographic (CT) scans such as might be obtained during a clinical stroke trial.

We studied CT scans from 18 stroke patients and 14 asymptomatic control patients obtained over 5 years at the San Diego Veterans Administration Medical Center. Three observers independently measured the volume of the cranial vault, cerebrum, cortex, white matter, deep gray structures, ventricle, sulcal cerebrospinal fluid space, visible infarction, and cerebellum/brain stem.

The two patient groups were well matched demographically. The intracranial volume of 1400 +/- 40 mL in control subjects was not different from the 1311 +/- 41 mL in patients. Cerebral volume was 1250 +/- 36 mL compared with 1070 +/- 36 mL (control subjects versus patients, P < .001), and infarction volume was 55 +/- 16 mL in patients. For all structures, intraclass correlation coefficients among the observers ranged from 0.87 to 0.03; the best agreement was found for lesion, ventricle, and intracranial volume. White matter and cortex volume predicted the National Institutes of Health Stroke Scale score but not the late outcome scores on the Barthel Index or Rankin Scale. Each scan required 70 to 90 minutes for analysis.

We developed a stereological method for cerebral morphometry from CT scans that is reliable, rapid, and simple. The measurements are unbiased, can be made on slices of any known thickness, and are independent of machine variables. Our results are remarkably similar to values obtained with more labor-intensive methods. This method should be of use in large-scale, multicenter trials of stroke therapy.
Transcranial color-coded duplex sonography in cerebral aneurysms.
Authors: Baumgartner R W , Mattle H P , Kothbauer K , Schroth G
Published: June 2011

Diagnosis and successful therapy before rupture of cerebral aneurysms would be most desirable in view of the high mortality and morbidity rates of aneurysmal subarachnoid hemorrhage. Using transcranial color-coded duplex sonography, we studied radiologically proven cerebral aneurysms to define ultrasonographic criteria and sensitivity for their diagnosis and detection.

Twenty-nine consecutive patients with 30 radiologically proven cerebral aneurysms were prospectively examined using transcranial color-coded duplex sonography. The sonographer was aware of cerebral computed tomographic and magnetic resonance imaging findings but was blinded to the results of cerebral angiography.

Ultrasonographic findings for aneurysms studied were as follows: (1) Scanning planes that transsected approximately mid-aneurysm showed a round or oval mass that was divided by a "separation zone" into red and blue areas. (2) The "separation zone" was characterized by dark or no colors. (3) Peripheral scanning planes showed monochromatic images. (4) No turbulence was found. (5) No spontaneous fluctuations were detected. Twenty-three of 27 (85%) nonthrombosed aneurysms with a diameter of 6 to 25 mm were identified. The walls and three thrombosed and four nonthrombosed aneurysms (mean diameter, 5 mm) were missed.

Transcranial color-coded duplex sonography can provide the diagnosis of nonthrombosed aneurysm using the above-cited criteria because of its capacity to reveal flow phenomena. It is not the method of choice in the search for aneurysms because small and thrombosed aneurysms are missed. Careful visual inspection of the intracranial arteries to permit incidental detection of cerebral aneurysms should be part of every transcranial color-coded duplex examination.
Disturbance of retention of memory after focal cerebral ischemia in rats.
Authors: Hirakawa M , Tamura A , Nagashima H , Nakayama H , Sano K
Published: June 2011

The purpose of this study was to investigate the behavioral changes, in particular retention of memory, after focal cerebral ischemia in rats.

Ischemia was produced by permanent occlusion of the left middle cerebral artery (MCA). For quantitative behavioral analysis, one-trial passive avoidance response and active avoidance response with the discrete lever-press avoidance procedure were observed. One group of animals was trained once to learn the passive avoidance task 1 day before surgery. The response latency was examined 4 and 14 days after surgery. The second group was trained to learn the active avoidance task for 2 weeks before surgery. The avoidance rate was examined 3 and 14 days after surgery.

The MCA-occluded group showed significant failure of memory retention in both of these tasks (P < .01). The nonoperated group and sham-operated group showed no definite memory failure.

Retention of memory in the passive avoidance response and the active avoidance response was disturbed after left MCA occlusion in the rat. These results strongly suggest that this model can be used to assess memory disturbance after focal cerebral ischemia.
Prothrombotic states in young people with idiopathic stroke. A prospective study.
Authors: Barinagarrementeria F , Cantú-Brito C , De La Peña A , Izaguirre R
Published: June 2011

Although 4% of cerebral infarcts in the young can be attributed to hematologic disturbances that predispose to thrombosis, the frequency of cerebral infarcts caused by prothrombotic states is not known. Recently, the association between cerebral infarction and deficiencies of elements of the natural anticoagulant system has been recognized.

Thirty-six consecutive patients under 40 years of age with cerebral infarction of undetermined cause were prospectively studied. Quantitation of natural anticoagulants was done at least 3 months after the cerebral infarction. The following activity tests were performed, all by the chromogenic method: antithrombin III, protein C, plasminogen, tissue plasminogen activator, and inhibitor of tissue plasminogen activator. Protein S was quantified by the Laurell rocket method. All patients underwent a complete cardiological examination, including two-dimensional echocardiography, as well as four-vessel cerebral angiography. Some patients were also studied by transesophageal echocardiography.

Of 36 patients, 17 were male, with a mean age of 28 years. Mean age for women was 25 years. Nine patients (25%; 5 women, 4 men) had a deficiency of one natural anticoagulant and constituted group I. In these patients, isolated protein S deficiency was detected in five cases (13.8%); in one case, we observed the association between protein S deficiency and antiphospholipid antibodies; and deficiency of protein C was seen in one case (2.7%), of antithrombin III in one case (2.7%), and of plasminogen in one case (2.7%). Instances of cerebral infarction without natural anticoagulant deficiency (group II) included 12 women and 15 men. There were no differences in clinical and radiological findings between the two groups.

Considering the importance of prothrombotic state, especially caused by deficiency of protein S, in the development of cerebral infarcts, we suggest that it should be looked for in every young patient affected by this pathological entity and in whom no etiologic factors can be determined.
Medical and neurological complications during inpatient stroke rehabilitation.
Authors: Dromerick A , Reding M
Published: June 2011

We sought to assess the type, frequency, and clinical predictors of neuromedical complications occurring during inpatient rehabilitation after stroke.

One hundred consecutive patient records were reviewed. All medical and neurological complications requiring a physician's order for further evaluation or treatment were recorded.

Complications were urinary tract infection (44 cases), depression (33), musculoskeletal pain (31), urinary retention (25), falls (25), fungal dermatitis (24), hypotension (19), diabetes mellitus (16), hypertension (15), and other neuromedical problem (194). The mean +/- SD numbers of medical and neurological complications per patient were 3.6 +/- 2 and 0.6 +/- 0.8, respectively. Complications were independently related to both the severity of functional disability as judged by Barthel score (r = -.42, P < .001) and length of rehabilitation hospital stay (r = .54, P < .001). Cardiac complications were predicted by New York Heart Association class 3 or 4 symptomatology on admission (P < .05). The age, sex, interval from stroke to rehabilitation hospital admission, and ischemic versus hemorrhagic etiology of the stroke were unrelated to the number of complications observed. Thirteen patients required transfer back to an acute-care hospital, one of whom died within 24 hours of transfer. There were no deaths on the rehabilitation unit.

We have defined the type and frequency of neuromedical complications during inpatient rehabilitation after stroke. Their frequency varies with the severity of stroke, cardiovascular comorbidity, and length of stay.
Usefulness of an intravenous contrast medium in the characterization of high-grade internal carotid stenosis with color Doppler-assisted duplex imaging.
Authors: Sitzer M , Fürst G , Siebler M , Steinmetz H
Published: June 2011

The remaining limitations of ultrasonographic imaging in accurately quantifying internal carotid stenosis or diagnosing internal carotid occlusion may be overcome by enhancing the echogenicity of flowing arterial blood with contrast agents. This study assessed the usefulness of the intravenous (transpulmonary) contrast medium SH U 508 A in improving the characterization and quantification of severe internal carotid stenosis.

We examined 32 patients (30 had vessels with a stenosis of greater than 70% luminal narrowing and 2 had vessel occlusions) using a 7.5-MHz linear-array transducer for color Doppler-assisted duplex imaging before and after injection of the contrast medium.

The SH U 508 A-induced increase in carotid blood echogenicity began 11 +/- 2 (mean +/- SD) seconds after the start of the bolus injection, peaked at 21 +/- 2 dB, and showed a half-life of 75 seconds. Quantitative vascular measurements (cross-sectional luminal area reduction and plaque length, respectively) obtained before and after contrast application were highly correlated (r > .90). Visualization of the entire length of the intrastenotic residual flow lumen, however, was significantly improved by contrast enhancement (52% versus 83%, P = .01).

This pilot study on patients with extracranial carotid artery disease suggested that ultrasonic contrast media may be most useful in improving the ultrasonography-based diagnosis of internal carotid occlusion.
Tissue-type plasminogen activator improves neurological functions in a rat model of thromboembolic stroke.
Authors: Sakurama T , Kitamura R , Kaneko M
Published: June 2011

The capacity of an intravenous infusion of double-stranded tissue-type plasminogen activator to salvage neurological functions in a rat model of thromboembolic stroke was studied.

The model of thromboembolic stroke was induced by the intracarotid injection of 2-hour-old homologous blood clots to rats. Neurological functions were scored on a 5-point scale 48 hours after the injection of the clots. Infarction size was determined by triphenyltetrazolium chloride staining, and cerebral hemorrhage was examined macroscopically.

Intravenous infusion of tissue-type plasminogen activator (1 or 5 x 10(5) IU/kg) within 3 hours after embolization significantly improved neurological functions (P < .01) and reduced infarction size (P < .05). Tissue-type plasminogen activator treatment 6 hours after embolization failed to attenuate the neurological status score. Treatment with tissue-type plasminogen activator did not increase the incidence of intracerebral hemorrhage and was not associated with a systemic fibrinolytic state. In comparison with tissue-type plasminogen activator treatment, although urokinase treatment (5 x 10(5) IU/kg) improved neurological functions, it was associated with a systemic fibrinolytic state and a tendency to increase the incidence of intracerebral hemorrhage.

These findings in this model suggest that tissue-type plasminogen activator should be given early after the onset of ischemic symptoms to effectively prevent or limit pathological infarction and improve neurological functions without an increase in the incidence of cerebral hemorrhage.
Effects of clentiazem on cerebral ischemia induced by carotid artery occlusion in stroke-prone spontaneously hypertensive rats.
Authors: Kikkawa K , Yamauchi R , Suzuki T , Banno K , Murata S , Tetsuka T , Nagao T
Published: June 2011

We examined metabolic and functional changes when forebrain ischemia was induced in stroke-prone spontaneously hypertensive rats by bilateral carotid artery occlusion. In addition, the protective effect of clentiazem was evaluated in this model.

Rats were anesthetized with urethane. Cerebral blood flow was measured with a laser Doppler flowmeter. Cerebral high-energy phosphates and intracellular pH were measured by phosphorus magnetic resonance spectroscopy. Electroencephalographic activity was evaluated as the summation of its amplitude. These parameters were monitored during a 30-minute period of ischemia and recirculation. Clentiazem was given orally as pretreatment (10 mg/kg twice a day for 3.5 days).

Bilateral carotid occlusion caused a decrease in cerebral blood flow to approximately 5% of the preischemic level and the disappearance of electroencephalographic activity. Occlusion also caused a decrease in ATP and phosphocreatine (to 48.7 +/- 4.3% and 23.7 +/- 2.2% of preischemic levels, respectively) as well as intracellular pH (from 7.3 +/- 0.1 to 6.0 +/- 0.1). During recirculation the reversal of these changes was variable: high-energy phosphates were partially restored, but electroencephalographic activity and intracellular pH showed little improvement. Hypoperfusion (55.7 +/- 11.5% of the preischemic flow) developed after reactive hyperemia. Pretreatment with clentiazem lessened the decrease in cerebral blood flow (control, 4.8 +/- 1.4%; clentiazem, 14.1 +/- 4.1% of the preischemic level; P < .05) and prevented the disappearance of electroencephalographic activity in some rats during ischemia. Clentiazem also prevented postischemic hypoperfusion and accelerated the restoration of high-energy phosphates, intracellular pH, and electroencephalographic activity during recirculation.

Carotid artery occlusion induced stable forebrain ischemia in stroke-prone spontaneously hypertensive rats. Clentiazem improved the metabolic and functional disturbances that occurred in this ischemic model, and its beneficial effect appeared to be due mainly to the relative preservation of cerebral blood flow during carotid occlusion.
Variations in the anatomy of the rabbit cervical carotid artery.
Authors: Lee J S , Hamilton M G , Zabramski J M
Published: June 2011

A model for cerebral ischemia that requires injection of emboli into the internal carotid artery of the rabbit is commonly used. However, in our experience we have found the anatomy of the cervical carotid to be highly variable. If not appreciated, this may result in unexpectedly high variability in the severity of ischemic injury. We undertook this experimental protocol to determine whether it was possible to characterize the anatomy of the rabbit cervical carotid artery.

We examined and recorded the architecture of the cervical carotid arteries of 105 consecutive rabbits involved in experimental protocols to evaluate the role of tissue-type plasminogen activator during embolic stroke.

Two basic patterns of origin of the internal carotid artery were identified: lateral origin, classified as type I, and dorsomedial origin, classified as type II. In addition, there were three subsequent variations in the origin and morphology of the occipital artery in relation to the internal carotid artery: origin from the external carotid artery (subtype A); origin proximal on the internal carotid artery (subtype B); and origin distal on the internal carotid artery (subtype C).

The classification of the anatomy of the cervical carotid artery of the rabbit into these easily recognized types will assist those attempting to use this embolization model. Failure to recognize the origin of the occipital artery from the internal carotid artery can result in the misdirection of embolic material into the occipital artery and significantly reduce the effectiveness of this stroke model.
Effects of cocaine on carotid vascular reactivity in swine after balloon vascular injury.
Authors: Núñez B D , Miao L , Ross J N , Núñez M M , Baim D S , Carrozza J P , Morgan J P
Published: June 2011

The use of cocaine has been associated with stroke. To evaluate carotid vasospasm as a potential mechanism of cocaine-induced stroke, we studied 12 swine immediately and 10 weeks after angioplasty.

We compared the short- and long-term vasoconstrictor responses of normal and injured arterial segments to nitroglycerin, histamine, and cocaine in vivo by carotid angiography. We also compared the isometric contractile force responses to different vasoactive substances in normal and injured vascular rings in vivo, and we tested the direct action of cocaine on both arterial segments.

In in vivo studies, immediately after angioplasty, luminal diameter in the control segment decreased by 30% with histamine 30 micrograms/kg and by 23% with cocaine 10 mg/kg (P < .001). In contrast, neither histamine nor cocaine produced vasoconstriction in the angioplasty segment. Thus, a transient loss of vasoconstriction occurred at the angioplasty site. Ten weeks later, histamine 30 micrograms/kg significantly (P < .001) decreased luminal diameter by 34% in the control and by 33% in the angioplasty segment; similarly, cocaine 10 mg/kg significantly (P < .001) decreased luminal diameter by 26% in the control and by 34% in the angioplasty segment. Thus, 10 weeks after angioplasty, the transitory loss of carotid vasoconstriction in response to histamine and cocaine reverted, and a moderate generalized vasoconstriction occurred in both segments without localized vasospasm. In vitro, the maximal isometric tension responses to KCl, acetylcholine, histamine, and phenylephrine were similar in vascular rings from normal and angioplasty segments. The median effective doses to histamine and phenylephrine were similar. In contrast, cocaine in concentrations from 10(-7) to 10(-3) mol/L failed to produce any isometric contraction in vitro.

Cocaine in vivo produced a generalized carotid vasoconstriction without evidence of localized vasospasm; since there was no response to cocaine in vitro, the in vivo effect was most likely mediated by neurohumoral factors rather than by a direct action of cocaine on vascular smooth muscle.
Effect of nilvadipine on the development of neurological deficits in stroke-prone spontaneously hypertensive rats.
Authors: Takakura S , Furuichi Y , Yamamoto T , Ogawa T , Satoh H , Mori J
Published: June 2011

Several types of antihypertensive drugs have been reported to protect stroke-prone spontaneously hypertensive rats from stroke. However, the clinical relevance remains unclear. This study was performed to investigate the effect of nilvadipine, a calcium channel blocker, on the development of neurological deficits in stroke-prone spontaneously hypertensive rats. In addition, plasma levels of nilvadipine were measured to determine the clinical relevance.

Salt-loaded stroke-prone spontaneously hypertensive rats were orally administered nilvadipine mixed with a powder diet (0.01% and 0.03%, wt/wt). Non-salt-loaded rats were maintained on tap water. Chronological changes in neurological deficit scores and systolic blood pressure were recorded. After 6 weeks of medication, measurement of plasma levels of nilvadipine, serum biochemical analysis, and pathological observation of both the brain and the kidney were performed.

In the salt-loaded control group, both severe hypertension and neurological deficit developed, and the final survival rate was 30%. Systolic blood pressure decreased significantly in the high-dose nilvadipine-treated group but not in the low-dose nilvadipine-treated group. However, the development of neurological deficit was almost completely inhibited in both nilvadipine-treated groups that had no deaths (P < .01). The mean plasma levels of nilvadipine in the low-dose group and in the high-dose group at the time of death were 0.21 ng/mL and 0.61 ng/mL, respectively.

Nilvadipine inhibited the development of neurological deficit in stroke-prone spontaneously hypertensive rats at plasma concentrations lower than that in clinical use. Thus, nilvadipine might prevent cerebral vascular disorders at doses routinely used for essential hypertension.