bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of CP101,606, a Novel NR2B Subunit Antagonist of the
N
-Methyl-
d
-Aspartate Receptor, on the Volume of Ischemic Brain Damage and Cytotoxic Brain Edema After Middle Cerebral Artery Occlusion in the Feline Brain
Authors: Di Xiao , Bullock Ross , Watson Joe , Fatouros Panos , Chenard Bertrand , White Frost , Corwin Frank
Published: June 2011

Background and Purpose
The purpose of this study was to test the hypothesis that the neuroprotective compound CP101,606 will ameliorate the increase in lactate, retard the development of cytotoxic edema, and decrease the infarct volume after ischemic stroke.

Methods
Seventeen adult cats were allocated to control (n=7) and CP101,606-treated groups (n=10). Transorbital middle cerebral artery occlusion was performed under anesthesia. Extracellular fluid lactate by microdialysis as well as infarct volume measurement by triphenyltetrazolium chloride (TTC)–stained section, with and without neuroprotective agents, was used to determine the value of these potential “surrogate markers” of ischemic damage.

Results
The control group showed an increased dialysate lactate (15.5% increase) at 30 minutes and a peak (332.0% increase) in dialysate lactate at 1 hour after middle cerebral artery occlusion compared with the drug-treated group. Significant differences between control and drug-treated groups were seen in the rate of fall of the apparent diffusion coefficient at both 1 and 5 hours. A close correlation was seen between the 1- and 5-hour apparent diffusion coefficient maps and the TTC-stained sections. There was a significantly smaller lesion in the CP101,606-treated group (62.9% reduction in infarct size compared with the control group;
P
<.001).

Conclusions
CP101,606 ranks very highly among the current neuroprotection candidates for clinical trials, and its excellent safety record in both animals and phase II studies in conscious, moderate head injury patients suggests that it will be highly effective in human occlusive stroke.
Diffusion-Weighted MRI in Transient Global Amnesia Precipitated by Cerebral Angiography
Authors: Woolfenden Andrew R. , O’Brien Michael W. , Schwartzberg Ross E. , Norbash Alexander M. , Tong David C.
Published: June 2011

Background
Transient global amnesia is a well-described complication of cerebral angiography. Speculation about the pathophysiology exists but is as yet unsubstantiated. Diffusion-weighted MRI is a new imaging technique that is very sensitive in detecting acute ischemia. Its use in the evaluation of transient amnesia precipitated by cerebral angiography has not previously been reported.

Case Description
A 44-year-old man underwent posterior circulation cerebral angiography for the investigation of episodic vertigo. Shortly after completion of the procedure, he was noted to have symptoms of transient global amnesia. Diffusion-weighted MRI at 6 and 44 hours after the procedure demonstrated increased signal in the right hippocampus and other areas within the posterior circulation bilaterally consistent with ischemia from emboli. Abnormalities on conventional MRI images performed at the same time points were noted only in retrospect. A follow-up MRI at 2 months was normal.

Conclusions
Ischemia from cerebral emboli may cause transient global amnesia precipitated by cerebral angiography. Diffusion-weighted MRI may be useful in defining the pathophysiology.
Surgical Closure of Patent Foramen Ovale in Cryptogenic Stroke Patients
Authors: Homma Shunichi , Di Tullio Marco R. , Sacco Ralph L. , Smith Craig , Mohr J. P.
Published: June 2011

Background and Purpose
Patent foramen ovale (PFO) is associated with stroke of unknown etiology or cryptogenic stroke. However, optimal treatment to prevent recurrence in cryptogenic stroke patients with PFO is not clearly defined. Since PFO represents a surgically repairable lesion, interest in closing it is high. This report reviews our experience with cryptogenic stroke patients with PFO who underwent surgical PFO closure and were followed for recurrence of neurological events.

Methods
We followed 28 cryptogenic stroke patients (17 men, 11 women; mean age, 41±13 years) with transesophageal echocardiograpy–defined PFO who had undergone PFO closure by open thoracatomy. All patients selected for surgery refused, could not take, or failed warfarin therapy. They were followed by physician visits and telephone interviews.

Results
There were no surgical complications. With a mean follow-up of 19 months, four patients experienced neurological event recurrence, one stroke, and three transient ischemic attacks. Kaplan-Meier survival analysis demonstrated that the actuarial rate of recurrence was 19.5% (95% confidence limit 2.2-36.8%) at 13 months of follow-up. None of the 17 patients (0%) younger than 45 years suffered a recurrence, whereas four of 11 patients (35%) aged 45 or older experienced a recurrence of neurological event (
P
<.02). Using a proportional hazards regression model, the increase in relative risk with increasing age was 2.76 per 10 years (95% confidence interval 1.07 to 7.16).

Conclusions
Although PFO is easily repairable in patients with cryptogenic stroke, its closure does not consistently prevent recurrence of ischemic events. The recurrence appears to occur more frequently in older cryptogenic stroke patients.
Poststroke Apathy and Regional Cerebral Blood Flow
Authors: Okada Kazunori , Kobayashi Shotai , Yamagata Shingo , Takahashi Kazuo , Yamaguchi Shuhei
Published: June 2011

Background and Purpose
Although apathy has been reported as one of the neuropsychiatric symptoms following stroke, there have been no studies on regional cerebral blood flow (rCBF) in patients with apathy. In this study we estimated the severity of apathy using the Apathy Scale and examined its relationship to rCBF in 40 stroke patients (mean age, 71.4 years).

Methods
Neuropsychiatric batteries were performed including the Apathy Scale, verbal intelligence and frontal function tests, a depression scale, and an assessment of activities of daily living. The cortical rCBFs were measured by the
133
Xe inhalation method.

Results
Twenty patients (50%) showed apathy. These patients showed significantly lower scores on verbal intelligence and frontal function tests and a significantly higher depression score than the nonapathetic group. On MRI images there was no relationship between the apathy score and specific regional distribution of lesions. The rCBFs of the bilateral hemisphere were significantly lower in the apathetic group than in the nonapathetic group. The apathetic group showed a significantly reduced rCBF in the right dorsolateral frontal and left frontotemporal regions. Furthermore, the apathy score for all patients was significantly negatively correlated with rCBF in the same regions.

Conclusions
These findings demonstrate that apathy is a frequent symptom among elderly stroke patients and may be accompanied by cognitive impairments, depressive state, and frontal dysfunction. The hypoactivity in the frontal lobe and anterior temporal regions may contribute to symptoms of apathy after stroke.
Trends in Case-Fatality of Stroke in Finland During 1983 to 1992
Authors: Immonen-Räihä Pirjo , Mähönen Markku , Tuomilehto Jaakko , Salomaa Veikko , Kaarsalo Esko , Narva Erkki V. , Salmi Kalervo , Sarti Cinzia , Sivenius Juhani , Alhainen Kari , Torppa Jorma
Published: June 2011

Background and Purpose
Stroke mortality has been declining in Finland during the past 20 years. It is not known, however, whether this favorable development is attributable to the decline in the incidence or case-fatality of stroke. For this reason we examined the trends in case-fatality of stroke, including trends by subtype of stroke.

Methods
The analyses were carried out using data of the community-based FINMONICA Stroke Register, which was operating in three geographic areas of Finland during 1983 to 1992. All stroke events (n=11 171) in persons aged 35 to 74 years were included in this register.

Results
The 28-day case-fatality of stroke fell yearly by 3.6% (
P
=.01) in men and by 2.6% (
P
=.2) in women. At the end of the study period, the average 28-day case-fatality of all strokes was 20% in men and 21% in women. Considerable differences by subtype of stroke were observed. The 28-day case-fatalities at the end of the study period were in men—56% for subarachnoid hemorrhage, 42% for intracerebral hemorrhage, and 14% for cerebral infarction. In women, the corresponding figures were 49%, 49%, and 14%. The 28-day case-fatality of subarachnoid hemorrhage did not change during the study period, but for intracerebral hemorrhage, a significant decline was observed in men and there was a declining trend also in women. The 28-day case-fatality of cerebral infarction declined significantly in both genders.

Conclusions
With the exception of subarachnoid hemorrhage, the 28-day case-fatality of stroke has fallen in Finland. It is likely that this fall has contributed to the decline in stroke mortality.
Timing of Carotid Endarterectomy After Stroke
Authors: Pritz Michael B.
Published: June 2011

Background
Timing of carotid endarterectomy after stroke in a patient with a fixed neurological deficit remains an important but unresolved question. Early surgery has been associated with cerebral hemorrhage and infarct extension. Delayed endarterectomy exposes the patient to recurrent stroke and carotid occlusion. This review investigates the hypothesis that timing of surgery after stroke influences outcome and complications.

Summary of Review
This analysis critically evaluates peer-reviewed reports that retrospectively examined outcome after surgery performed “early” and “late” after stroke. The basis for intracerebral hemorrhage after endarterectomy is discussed. Clinical features that influence outcome are investigated.

Conclusions
Patients undergoing carotid endarterectomy are considered a heterogeneous group based on the following features: presence of low density on cranial CT, vascular territory of the infarct, brain shift, and level of consciousness. While critical review of these retrospective studies suggests that some patients with an acute stroke can safely undergo endarterectomy shortly after the diagnosis is made, direct answers to these questions of timing of endarterectomy after stroke are best addressed by prospective studies. Nevertheless, the present review provides a basis for decision making in certain patients and for the design of future investigations.
Atrial Fibrillation and Stroke
Authors: Kaarisalo Minna M. , Immonen-Räihä Pirjo , Marttila Reijo J. , Salomaa Veikko , Kaarsalo Esko , Salmi Kalervo , Sarti Cinzia , Sivenius Juhani , Torppa Jorma , Tuomilehto Jaakko
Published: June 2011

Background and Purpose
Atrial fibrillation (AF) is a risk factor for stroke. This study was undertaken to determine the influence of AF on the mortality of stroke patients and on the causes of death after a stroke event.

Methods
Patients with first ischemic stroke who were 35 to 74 years old and registered in the FINMONICA stroke register during 1982 through 1992 were analyzed (n=6912). There were 642 patients with AF (9.3%) (mean age, 67 years) and 6270 patients without AF (90.3%) (mean age, 63 years). The association between AF and stroke mortality was investigated by use of logistic regression and Cox proportional hazards models.

Results
Mortality was higher in the AF group both at 28 days (19.5% versus 14.4%,
P
<.001) and 1 year after the attack (30.5% versus 21.8%,
P
<.001). After adjustment for age and sex, the odds ratio for 28-day case fatality (AF versus non-AF) was 1.27 (95% CI, 1.03 to 1.56;
P
=.003), and that for 1-year mortality was 1.36 (95% CI, 1.14 to 1.63;
P
<.001). In the proportional hazards model, AF was a significant independent risk factor for 1-year mortality (hazard ratio, 1.26; 95% CI, 1.09 to 1.46;
P
=.002). Cardiac causes of death were more common in the AF group at the acute stage. In the course of 1 year, there were no differences in the distributions of causes of death.

Conclusions
Stroke patients with AF are at high risk of death both at the acute phase of stroke and during the subsequent year after the first acute stroke event. Mortality from cardiac diseases prevailed in the AF group during the acute phase of stroke. Careful cardiac evaluation and treatment are essential in patients with AF and stroke.
Spreading of Vasogenic Edema and Cytotoxic Edema Assessed by Quantitative Diffusion and T2 Magnetic Resonance Imaging
Authors: Loubinoux I. , Volk A. , Borredon J. , Guirimand S. , Tiffon B. , Seylaz J. , Méric P.
Published: June 2011

Background and Purpose
The apparent diffusion coefficient (ADC) of water should be sensitive to the cytotoxic edema triggered by energy failure during ischemia. Elevated values of T2, the nuclear MR transverse relaxation time of water, seen on T2 nuclear MR images detect vasogenic edema and infarcted areas. The temporal and spatial changes in ADC and T2 abnormalities after occlusion of the middle cerebral artery (MCAO) were therefore estimated by these two quantitative techniques.

Methods
Permanent MCAO was performed on rats. Quantitative ADC and T2 maps of brain water were obtained, from which the ischemic volumes were calculated at various times up to 48 hours after MCAO.

Results
The areas of decreased ADC represented 36±7% of the final infarct volume (24 hours) at 0.5 hours and 64±4% at 5 hours after MCAO, suggesting that there is recruitment of peripheral areas with disturbed energy metabolism and cytotoxic edema. The ADC and T2 contours closely matched at 3.5, 24, and 48 hours after MCAO.

Conclusions
T2 imaging can assess ischemic insults as well as ADC imaging, but only 3.5 hours after the onset of ischemia. Assessment of edematous swelling (≈24.5% of total infarcted volume) demonstrates that ADC and therefore T2 imaging detect all the tissue that will become infarcted approximately 7 hours after occlusion. The spread of ADC and T2 abnormalities would therefore stop at approximately 7 hours, and any further increase in volume observed on the images would be mainly due to edematous swelling.
Role of Potassium Channels in Relaxations of Isolated Canine Basilar Arteries to Acidosis
Authors: Kinoshita Hiroyuki , Katusic Zvonimir S.
Published: June 2011

Background and Purpose
Concentration of hydrogen ions is an important regulator of cerebral arterial tone under physiological and pathological conditions. Previous studies demonstrated that in cerebral arteries, relaxations to hypercapnia are due to decrease in extracellular pH. The present study was designed to determine the role of potassium channels in mediation of cerebral arterial relaxations induced by extracellular acidosis.

Methods
Rings of canine basilar arteries without endothelium were suspended for isometric force recording. Acidosis (pH 7.3 to 7.0) was produced by incremental addition of hydrochloric acid (1.0N). The concentration of hydrogen ions was continuously monitored with a pH meter.

Results
During contractions to UTP, acidosis (pH 7.3 to 7.0) induced pH-dependent relaxations. These relaxations were abolished in arteries contracted by potassium chloride (20 mmol/L). A nonselective potassium channel inhibitor, BaCl
2
(10
−3
and 10
−4
mol/L), and an ATP-sensitive potassium channel inhibitor, glyburide (5×10
−6
mol/L), significantly reduced relaxations to acidosis. Furthermore, BaCl
2
(10
−3
mol/L) and glyburide (5×10
−6
mol/L) abolished relaxations to an ATP-sensitive potassium channel opener, cromakalim (10
−8
to 3×10
−5
mol/L). However, these potassium channel inhibitors did not affect relaxations to a voltage-dependent calcium channel inhibitor, diltiazem (10
−8
to 10
−4
mol/L), and glyburide (5×10
−6
mol/L) did not alter relaxations to a nitric oxide donor, SIN-1 (10
−9
to 10
−4
mol/L). A calcium-activated potassium channel inhibitor, charybdotoxin (10
−7
mol/L), and a delayed rectifier potassium channel inhibitor, 4-aminopyridine (10
−3
mol/L), did not affect relaxations to acidosis.

Conclusions
These results suggest that extracellular acidosis causes relaxations of cerebral arteries in part by activation of potassium channels. ATP-sensitive potassium channels appear to contribute to acidosis-induced decrease in cerebral arterial tone.
Duplex Ultrasound Criteria for the Identification of Carotid Stenosis Should Be Laboratory Specific
Authors: Kuntz Karen M. , Polak Joseph F. , Whittemore Anthony D. , Skillman John J. , Kent K. Craig
Published: June 2011

Background and Purpose
Published criteria for the determination of carotid stenosis have been widely applied by vascular laboratories. We compared two vascular laboratories and their duplex ultrasound (DU) machines in terms of their overall diagnostic performance and the optimal criteria to identify patients who have a 70% to 99% stenosis of the internal carotid artery.

Methods
Measurements of stenosis by DU and angiography were compared for 123 carotid arteries (60 arteries, laboratory A; 63 arteries, laboratory B). Receiver operating characteristic (ROC) curves were created, and the areas under the ROC curves and the optimal criteria for determining a 70% to 99% stenosis were compared. Multiple regression analysis was used to measure the effect of laboratory on the relationship between angiographic stenosis and DU velocity parameters.

Results
Areas under the ROC curves were similar for both laboratories (0.89 to 0.90, laboratory A; 0.90 to 0.92, laboratory B). However, the optimal criterion for the identification of a 70% to 99% carotid stenosis was different for each laboratory. For most velocity parameters, based on regression analyses, the predicted percent angiographic stenosis for laboratory A was significantly greater than that for laboratory B. In addition, performance differed between the laboratories when established criteria from the literature were applied.

Conclusions
Two vascular laboratories with similar diagnostic accuracy by ROC analysis have markedly different “optimal” DU criteria. For a given angiographic stenosis, velocities in one laboratory were consistently greater than those in the other laboratory. Laboratory-specific criteria rather than published criteria should be used to identify patients with internal carotid artery stenoses.
Subdural Hematoma and Lupus Anticoagulants
Authors: Moll Stephan , McCloud Michael , Ortel Thomas L.
Published: June 2011

Background and Purpose
Patients with lupus anticoagulants do not typically have a bleeding tendency. However, a few reports of hemorrhage in patients with lupus anticoagulants in the absence of known risk factors for bleeding have been published, raising the question of an etiologic connection between lupus anticoagulants and certain types of hemorrhage. The presentation of three patients with subdural hematoma and lupus anticoagulants within only 1 year at our institutions and the report of two such patients in the literature led us to conduct a retrospective study to determine whether patients with lupus anticoagulants may have an increased risk for the development of subdural hematoma.

Case Descriptions
All patients with a discharge diagnosis of nontraumatic subdural hematoma and lupus anticoagulant at three medical institutions between 1985 and 1996 were identified, and their medical histories and laboratory evaluations were reviewed. Of 733 patients with a discharge diagnosis of nontraumatic subdural hematoma, 5 were diagnosed as having a lupus anticoagulant (0.7%). All had known risk factors for the development of subdural hematoma: thrombocytopenia, hypoprothrombinemia, intracerebral venous hemorrhage, warfarin therapy, and advanced age with a history of a fall.

Conclusions
This study suggests that presence of a lupus anticoagulant by itself is not associated with an increased incidence of nontraumatic subdural hematoma.
Hospitalization and Case-Fatality Rates for Subarachnoid Hemorrhage in Canada From 1982 Through 1991
Authors: Østbye Truls , Levy Adrian R. , Mayo Nancy E.
Published: June 2011

Background and Purpose
Subarachnoid hemorrhage (SAH) has a different epidemiological profile from other types of stroke and a different etiology. Although there has been a general decline in overall stroke incidence since the 1950s, secular trends for SAH have been modest. In contrast to other stroke types, changes in incidence over the last few decades have been less clear. The purpose of this study was to estimate hospitalization and case-fatality rates of SAH according to age, sex, calendar year, and season.

Methods
Data were obtained for each of Canada’s 10 provinces for the 10 fiscal years 1982 through 1991. All hospitalizations of persons 15 years of age or older with a primary diagnosis at discharge coded 430 according to the
International Classification of Diseases, 9th Revision,
were included. Rates of SAH per 100 000 population were calculated for men and women for 5-year age groups, by calendar year, and by season. Annual age- and sex-specific (hospital) case-fatality rates up to 30 days were also calculated. Additionally, hospital deaths from this study were related to national SAH mortality statistics.

Results
A total of 14 145 women and 8995 men were discharged with a primary diagnosis of SAH during the 10-year period. In contrast to other types of stroke, the rates of SAH were higher for women than for men at all ages. The age-standardized rates of SAH in 1991-1992 were 11.2 per 100 000 women and 8.0 per 100 000 men. For women, there was a 6% (95% confidence interval [CI], −12% to 0%) decline in hospitalization rates over that period; for men, the decline was 15% (95% CI, −21% to −8%). The peak season for SAH among women was winter; for men the peaks were in the fall and spring. For both sexes, the lowest occurrence was in the summer. Over this period, 30-day case-fatality rates declined somewhat (statistically significant only in the age group of 35 to 44 years). The number of deaths enumerated from hospital discharges was 20% to 50% lower than the number recorded on national mortality statistics, indicating that a proportion of SAH deaths occurred before (or after) the hospital stay.

Conclusions
Although rates of hospitalization for SAH declined over this period, SAH remains an important neurological event affecting individuals at relatively young ages. The rates were higher for women than for men at all ages. Total (in-hospital) case-fatality rate remains high.
Isoprostanes: Free Radical–Generated Prostaglandins With Constrictor Effects on Cerebral Arterioles
Authors: Hoffman Stuart W. , Moore Sandra , Ellis Earl F.
Published: June 2011

Background and Purpose
Isoprostanes are generated by cyclooxygenase-independent free radical attack of arachidonic acid and are potent constrictors of the peripheral vasculature. Traumatic brain injury stimulates oxygen radical production and is associated with cerebral blood flow reduction. However, no specific vasoconstrictor has been identified as the cause of posttraumatic blood flow reduction. The purpose of this study was to determine whether isoprostanes constrict cerebral arterioles.

Methods
The effects of 10
−9
to 10
−5
mol/L 8-iso-prostaglandin F
2α
(8-iso-PGF
2α
), 8-iso-prostaglandin E
2
(8-iso-PGE
2
), and prostaglandin F
2α
(PGF
2α
) on pial arteriolar diameter were measured in anesthetized rats using a closed cranial window and in vivo microscopy.

Results
All prostanoids produced vasoconstriction. Of these, 8-iso-PGF
2α
produced the greatest vasoconstriction (34%±2), followed by 8-iso-PGE
2
(25%±4) and PGF
2α
(20%±2). After six cerebrospinal fluid washouts of the cranial window, both 8-iso-PGF
2α
– and 8-iso-PGE
2
–treated vessels remained slightly constricted, whereas the PGF
2α
-treated vessels returned to control diameter. Coapplication of the semiselective thromboxane A
2
/prostaglandin H
2
receptor antagonist SQ29548 completely blocked the vasoconstriction induced by 8-iso-PGF
2α
and 8-iso-PGE
2
.

Conclusions
Isoprostanes are potent constrictors of cerebral arterioles and appear to act at a receptor that is similar to the thromboxane A
2
/prostaglandin H
2
receptor. Isoprostanes may play a role in the reduction of cerebral blood flow that occurs after brain injury and subsequent oxygen radical production.
Characterization of Ionotropic Glutamate Receptor–Mediated Nitric Oxide Production In Vivo in Rats
Authors: Bhardwaj Anish , Northington Frances J. , Ichord Rebecca N. , Hanley Daniel F. , Traystman Richard J. , Koehler Raymond C.
Published: June 2011

Background and Purpose
Glutamate receptor activation can stimulate nitric oxide (NO) production and possibly play a role in long-term potentiation and excitotoxic-mediated injury. We studied the differential effect of agonist-induced activation of ion channel–linked
N
-methyl-
d
-aspartate (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subtypes on NO production in vivo in rat hippocampus. We also studied whether dantrolene, a ryanodine calcium channel inhibitor previously shown to attenuate metabotropic glutamate receptor stimulation of NO production, also attenuated ionotropic glutamate receptor–mediated stimulation of NO production.

Methods
Microdialysis probes were placed bilaterally into the CA3 region of the hippocampus of pentobarbital-anesthetized adult Sprague-Dawley rats and were perfused for 5 hours with artificial cerebrospinal fluid (CSF) containing 3 μmol/L [
14
C]
l
-arginine. Recovery of [
14
C]
l
-citrulline in the effluent was used as a marker of NO production. In 13 groups of rats, increases in [
14
C]
l
-citrulline recovery were compared between right- and left-sided probes perfused with no additional drugs versus combinations of NMDA, AMPA, the NO synthase inhibitor
N
ω
-nitro-
l
-arginine methyl ester (L-NAME), the noncompetitive glutamate receptor blocker MK-801, the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and dantrolene.

Results
Recovery of [
14
C]
l
-citrulline during perfusion with artificial CSF progressively increased to 272±73 fmol/min (±SEM) over 5 hours. Contralateral perfusion with 1 mmol/L L-NAME inhibited [
14
C]
l
-citrulline recovery. Perfusion with 1 mmol/L MK-801 or 1 mmol/L CNQX reduced [
14
C]
l
-citrulline recovery compared with contralateral perfusion with CSF alone. Perfusion with 1 mmol/L NMDA enhanced [
14
C]
l
-citrulline recovery, and this enhancement was attenuated by L-NAME, MK-801, and CNQX but not by dantrolene. Perfusion with 1 mmol/L AMPA enhanced [
14
C]
l
-citrulline recovery, and this enhancement was also attenuated by L-NAME, MK-801, and CNQX but not by dantrolene.

Conclusions
Through an indirect method of assessing NO production in vivo, results with MK-801 and CNQX indicate that NMDA and AMPA receptor activation contribute to basal NO production in the rat hippocampus. Enhanced NO production with NMDA and AMPA agonists appears to involve a complex neuronal interaction because the effect of NMDA was attenuated by both MK-801 and CNQX and because the effect of AMPA was attenuated by both CNQX and MK-801. In contrast to metabotropic glutamate receptor activation, release of calcium from intracellular ryanodine calcium channels does not appear to be a prominent mediator of ionotropic glutamate receptor stimulation of NO production.
Characterizing the Target of Acute Stroke Therapy
Authors: Fisher Marc
Published: June 2011

Background
The development of effective therapies for acute ischemic stroke presumes the existence of potentially salvageable ischemic tissue when therapy is initiated because it is widely assumed that the effectiveness of most acute stroke therapies under development is related to reducing ultimate infarct size to promote functional improvement. Such salvageable ischemic tissue was previously labeled the ischemic penumbra and must be distinguished from irreversible injury.

Summary of Review
Pathological identification of irreversibility (infarction) appears to lag behind the actual development of this condition, and reversible injury after focal ischemia should be differentiated from infarction. Imaging and biochemical markers apparently can provide clues for distinguishing potentially salvageable from irreversibly injured ischemic tissue in experimental and clinical stroke. Recent positron emission tomography and MRI studies suggest that these clinically available imaging technologies will be useful for determining the presence of ischemic penumbra in individual stroke patients. The progression from potentially reversible to irreversible injury after focal brain ischemia has many potential mechanisms that may be synergistic and vary among individuals.

Conclusions
Delineating and prioritizing these mechanisms provides the opportunity to develop multiple potential acute stroke therapies that ultimately will be used in combination, perhaps directed by imaging technology.
Neurological Signs and Frontal White Matter Lesions in Vascular Parkinsonism
Authors: Yamanouchi Hiroshi , Nagura Hiroshi
Published: June 2011

Background and Purpose
The clinical characteristics and the pathological lesions of so-called vascular parkinsonism (VP) are still debatable. The purpose of this study was to define the core signs and symptoms and assess the cerebrovascular lesions in pathologically confirmed VP.

Methods
In the present study, VP was defined as the presence of parkinsonism and pathological evidence of cerebrovascular lesions but no depigmentation or Lewy bodies at the substantia nigra. We compared the clinical signs and symptoms of 24 VP patients with those of 30 age-matched patients with pathologically confirmed Parkinson’s disease. We compared the brain pathology in VP patients with that in 22 age-matched patients with Binswanger’s disease (BD) who had no parkinsonism according to clinical records.

Results
VP was characterized clinically by a short-stepped or frozen gait, lead-pipe rigidity, absence of resting tremor, and negative response to levodopa. Half or more of VP patients demonstrated pyramidal tract signs and pseudobulbar palsies. There was no significant difference in the extent of vascular lesions at the basal ganglia between patients with VP and with BD without parkinsonism. The extent of frontal white matter pallor tended to be less broad in VP than in BD without parkinsonism. In VP patients, the number of oligodendrocytes in the frontal white matter was significantly less than that in age-matched normal control subjects and significantly more than in those with BD.

Conclusions
The core signs and symptoms of autopsy-proved VP differ from those of typical Parkinson’s disease, and most VP patients had diffuse cerebral white matter lesions as well as basal ganglia lesions. VP might be related to frontal white matter lesions.
Low-Velocity Graded Treadmill Stress Testing in Hemiparetic Stroke Patients
Authors: Macko R. F. , Katzel L. I. , Yataco A. , Tretter L. D. , DeSouza C. A. , Dengel D. R. , Smith G. V. , Silver K. H.
Published: June 2011

Background and Purpose
Coronary artery disease is prevalent in stroke patients and is an important factor affecting rehabilitation and health outcomes. However, the presence of neurological deficits in gait and balance has discouraged systematic application of exercise testing and prescription in the stroke population. We evaluated a novel graded treadmill stress test in paretic stroke patients and tested floor walking as a predictor of adequate neurological function to perform the treadmill test.

Methods
Patients (n=31) with residual paretic gait deficits after ischemic stroke were evaluated with graded treadmill at gait velocities individualized to functional mobility observed during an initial zero-incline treadmill tolerance test.

Results
Most patients (30/31) tolerated testing, achieving mean heart rates of 129±14 beats per minute (mean±SD), representing 84±10% of maximal age-predicted heart rate. Evidence for asymptomatic myocardial ischemia was found in 29% of those without known coronary artery disease. Exercise termination was more often due to generalized fatigue than cardiopulmonary intolerance (23/31 versus 4/31;
P
<.0001) or hemiparetic leg fatigue (1/31;
P
<.0001). Floor walking across a wide range of velocities (0.25 to 2.5 mph) demonstrated a strong linear relation with treadmill velocities (n=24;
r
=.80;
P
<.0001); all patients floor walking at ≥0.5 mph had adequate neuromotor function to perform the exercise test.

Conclusions
These findings suggest that graded treadmill exercise testing, with proper safety precautions, can be used to assess cardiopulmonary function in paretic stroke patients. A simple floor-walking test predicts adequate neurological function to perform the exercise test. Exercise capacity is most limited by generalized fatigue and not by the paretic limb, supporting a rationale for endurance training in this population.
In Vivo Association Between Low Wall Shear Stress and Plaque in Subjects With Asymmetrical Carotid Atherosclerosis
Authors: Gnasso Agostino , Irace Concetta , Carallo Claudio , De Franceschi Maria Serena , Motti Corradino , Mattioli Pier Luigi , Pujia Arturo
Published: June 2011

Background and Purpose
It is known that atherosclerosis does not involve both carotid arteries to the same extent. Pathological investigations have demonstrated that lesions develop in regions of low wall shear stress. The aims of the present study were to verify the degree of carotid atherosclerosis asymmetry in a population-based study and to evaluate whether wall shear stress is lower in carotids with atherosclerotic lesions than in carotids without lesions.

Methods
Participants in a cardiovascular disease prevention campaign (n=1166) were screened for carotid atherosclerosis by echo-Doppler examination. Of these, 23 subjects who presented plaque in the common carotid or bulb of one side and no plaque in the contralateral carotid tree were enrolled for common carotid wall shear stress measurement. Shear stress was calculated according to the following formula: Shear Stress=Blood Viscosity×Blood Velocity/Internal Diameter.

Results
Of the 1166 subjects screened, 400 (34%) had plaque and/or stenosis in the carotids. Ninety subjects had lesions exclusively in the right carotid, 111 had lesions exclusively in the left, 70 had lesions in both carotids but with different degrees of severity, and only 129 had similar lesions in both carotids. In the 23 subjects in whom wall shear stress was measured, peak shear stress was 18.7±4.1 and 15.3±4.0 dynes·cm
−2
(mean±SD) (
P
<.0001) in the side without and the side with plaque, respectively. Mean shear stress yielded similar results.

Conclusions
The present results demonstrate that the atherosclerotic involvement of carotid arteries is usually asymmetrical and that wall shear stress is lower in the carotid arteries where plaques are present than in plaque-free arteries. These findings provide in vivo evidence for a strong association between shear stress and atherosclerotic lesions.
Ischemic Cerebral Infarction After rt-PA and Heparin Therapy for Acute Myocardial Infarction
Authors: Sloan Michael A. , Price Thomas R. , Terrin Michael L. , Forman Sandra , Gore Joel M. , Chaitman Bernard R. , Hodges Morrison , Mueller Hiltrud , Rogers William J. , Knatterud Genell L. , Braunwald Eugene
Published: June 2011

Background and Purpose
Ischemic cerebral infarction (CI) is a serious complication of acute myocardial infarction (MI). Little information exists on CI after thrombolytic therapy for MI.

Methods
Of 3924 MI patients treated with recombinant tissue plasminogen activator (rt-PA) and heparin, 29 (0.7%) developed CI after treatment. All CI patients had detailed neurological evaluations, and 27 (93%) had CT scans centrally reviewed.

Results
Age range was 40 to 74 years (mean, 60 years); 25 patients (86%) were men, and 22 (76%) were white. The electrocardiographic location of MI was anterior in 22 (76%) and nonanterior in 7 (24%). Five CIs occurred within 6 hours, 4 between 6 to 24 hours, 8 during the remainder of the first week, 10 during the second week, and 2 others distributed over the 4 weeks after study entry. Six of 29 CIs did not involve the cerebral cortex; 9 patients (31%) had multiple CIs. Of 28 CIs thought to be embolic in origin, 17 showed strong evidence for at least one cardiac abnormality (mural clot, wall-motion abnormality, aneurysm, or atrial fibrillation) known to be associated more specifically with embolism than MI. Eight of 27 CIs (30%) with CT scans had hemorrhagic transformation of varying degrees; 5 were symptomatic.

Conclusions
The time of occurrence and sites of CI after rt-PA and heparin therapy for acute MI are similar to those reported during the prethrombolytic era.
Psychosocial Stressors in Patients With Major Depression and Silent Cerebral Infarction
Authors: Fujikawa Tokumi , Yanai Ichiro , Yamawaki Shigeto
Published: June 2011

Background and Purpose
We previously found that silent cerebral infarction (SCI) was present in most of the patients older than 50 years with major depression who were examined. The present study was designed to clarify the relationship between psychosocial stressors and SCI in patients with major depression.

Methods
Forty-two patients with unipolar depression underwent MRI and were classified as SCI-negative (n=19) or SCI-positive (n=23). The SCI-positive group was subclassified into those with moderate SCI (n=16) and those with severe SCI (n=7). The relationship between the patients’ DSM-III-R axis IV scores and SCI was evaluated.

Results
The axis IV score was significantly lower in the SCI-positive group than in the SCI-negative group (
P
<.05). Within the SCI-positive group, the mean axis IV score was significantly lower in those with severe SCI than in those with moderate SCI (
P
<.05).

Conclusions
Our findings suggest that depression in patients with SCI involves more neurological factors than psychosocial stressors.
Cerebral Vascular Malformations Adjacent to Sensorimotor and Visual Cortex
Authors: Schlosser Michael J. , McCarthy Gregory , Fulbright Robert K. , Gore John C. , Awad Issam A.
Published: June 2011

Background and Purpose
It is not known how cerebral vascular malformations affect the function of the surrounding brain. Functional magnetic resonance imaging (fMRI) can provide information about normal functional neuroanatomy and its alteration by vascular lesions and therapeutic intervention.

Methods
We performed fMRI studies in 24 patients harboring vascular malformations adjacent to primary somatosensory, motor, and visual cortex. The fMRI studies consisted of the acquisition of an image time series coupled with functional activation of motor, sensory, or visual cortex in both hemispheres. Activated voxels were identified using frequency domain analyses, and their number and anatomic location were compared between the affected and unaffected hemispheres.

Results
Every patient capable of performing the desired task showed functional activation. Eight patients without neurological deficits showed a symmetrical pattern of activation between the hemispheres. Each had a vascular malformation located one or more gyri from the functional region imaged. Three patients showed hemispheric symmetry in the location of activated cortex but with a marked asymmetry in the number of activated voxels. Each harbored vascular malformations located within one gyrus of the functional region and showed either subtle or no neurological deficit. Eleven patients showed hemispheric asymmetry in the location of activated cortex. In 6, the anatomic displacement appeared to be due to a mass effect of the lesion. In 5, the activation occurred at a different anatomic locale, and the patients exhibited gross neurological deficit in the respective function. Posttherapeutic changes in functional activation reflected elimination of the mass effect or recovery of clinical function.

Conclusions
Systematic fMRI studies are possible in patients with vascular malformations in brain regions adjacent to primary somatosensory, motor, and visual cortex. Displacement of the activated region and hemispheric asymmetry in the number of activated voxels in the functional regions appear to reflect the anatomic and physiological impact of the vascular malformation. Changes in fMRI findings after intervention reflect the consequences of therapy and parallel clinical recovery.
Retrospective Assessment of Initial Stroke Severity With the Canadian Neurological Scale
Authors: Goldstein Larry B. , Chilukuri Vani
Published: June 2011

Background and Purpose
The severity of the initial neurological deficit is a critical determinant of outcome after acute stroke. Retrospective outcome studies are generally limited by a lack of quantitative data relating to this initial stroke severity. We evaluated the validity and reliability of measuring initial stroke severity retrospectively with the Canadian Neurological Scale (CNS).

Methods
The CNS was used to prospectively score the initial neurological deficit in a series of patients with acute ischemic stroke (n=24). An algorithm was devised for applying the CNS retrospectively on the basis of information in the patient’s hospital discharge summary. Those dictating the discharge summaries were not aware of the study, and the retrospective scoring was performed without reference to other scores. The level of agreement between the prospective and retrospective scores (validity) and both intraobserver and interobserver reliability for the retrospective scores were determined.

Results
Agreement was high between retrospective and prospective scores (
r
=.84,
R
2
=.71,
P
<.0001), between two sets of retrospective scores obtained by one rater (
r
=.95,
R
2
=.91,
P
<.0001), and between retrospective scores obtained by different raters (
r
=.91,
R
2
=.82,
P
<.0001). Weighted kappa statistics (κ
w
) for prospectively versus retrospectively scored items varied from almost perfect (κ
w
>0.81 for level of consciousness and orientation) to substantial (κ
w
=0.68 for speech) and moderate (κ
w
=0.41 to 0.60 for facial weakness, proximal arm, distal arm, proximal leg, and distal leg strength). Using the retrospective algorithm, there was almost perfect intraobserver and interobserver reliability for each of the individual CNS items (κ
w
=0.81 to 1.00).

Conclusions
These data show that retrospective scoring of initial stroke severity using an algorithm based on the CNS is valid and can be reliably performed using information available in hospital discharge summaries.
In Vivo Angioplasty Prevents the Development of Vasospasm in Canine Carotid Arteries
Authors: Megyesi Joseph F. , Findlay J. Max , Vollrath Bozena , Cook David A. , Chen Ming H.
Published: June 2011

Background and Purpose
To study the effects of in vivo transluminal balloon angioplasty (TBA) on the structure and function of the arterial wall, a canine model of hemorrhagic cerebral vasospasm of the high cervical internal carotid artery (ICA) was used. This model was also used to determine whether TBA performed before clot placement could prevent the development of vasospasm.

Methods
Twelve dogs underwent surgical exposure of both distal cervical ICAs, followed by baseline angiography. One randomly selected ICA in each dog was then subjected to in vivo TBA and repeated angiography. Both distal ICAs were then surrounded with blood clots held by silicone elastomer sheaths. Seven days later angiography was repeated, and all animals were killed. The ICAs in four animals were perfusion-fixed in situ for morphological analysis by electron microscopy, and the arteries in the remaining eight animals were removed and immediately immersed in oxygenated Krebs’ solution. Contractile responses of isolated arterial rings from each ICA were recorded after treatment with KCl, noradrenaline, serotonin, and prostaglandin F
2α
, while relaxations in response to the calcium ionophore A23187 and papaverine were recorded after tonic contraction to noradrenaline had been established. The morphology and pharmacological responses of ICAs that had been exposed to blood with or without prior TBA were compared with data obtained from control arterial segments of intact, more proximal regions of the ICAs from each animal.

Results
TBA resulted in immediate angiographic enlargement of the ICA lumen that was still evident 7 days later despite the placement of clotted blood around the artery. Scanning and transmission electron microscopy demonstrated flattening of the intima and internal elastic lamina in these dilated arteries, associated with patchy losses of endothelial cells. In contrast, ICAs that had been exposed to clotted blood but had not undergone prior TBA developed consistent angiographic and morphological vasospasm. In comparison with control vessels and nondilated vasospastic vessels, vessels dilated with TBA and then exposed to clotted blood showed significantly diminished responses to all compounds tested, with the exception of prostaglandin F
2α
.

Conclusions
These results indicate that in vivo TBA results in a degree of functional impairment of vascular smooth muscle that persists for at least 7 days. This result is consistent with previous observations of the acute effects of TBA in isolated arteries. Furthermore, these results support the hypothesis that normal smooth muscle function is required for the development of vasospasm. Finally, these results indicate that TBA performed before the onset of vasospasm prevents its development.
Neural Grafting to Experimental Neocortical Infarcts Improves Behavioral Outcome and Reduces Thalamic Atrophy in Rats Housed in Enriched but Not in Standard Environments
Authors: Mattsson Bengt , Sørensen Jens Christian , Zimmer Jens , Johansson Barbro B.
Published: June 2011

Background and Purpose
The purpose of this study was to evaluate whether grafting of fetal neocortical tissue 1 week after focal brain ischemia improved behavioral outcome and reduced secondary thalamic atrophy.

Methods
One week after distal ligation of the right middle cerebral artery in spontaneously hypertensive male rats, blocks of fetal neocortex (embryonic day 17) were homografted to rats housed in standard or enriched environments. Control infarcted nongrafted rats were housed in the enriched environment. Behavioral outcome was repeatedly tested until the rats were killed 20 weeks after the ligation. Ten days earlier, a mixture of 2% Fluoro-Gold and 10% biotinylated dextran amine was injected into the transplants for retrograde and anterograde tracing of graft-host connections.

Results
Grafted and nongrafted rats with enriched housing performed significantly better than grafted rats with standard housing on a rotating pole and a prehensile traction test. Grafted “enriched” rats were moreover significantly better than grafted “standard” rats and nongrafted enriched rats in a rotation test and a postural and locomotor tail position test. In the latter test, nongrafted enriched rats performed significantly better than grafted standard rats. The lesion-induced atrophy in posterior thalamus with its major sensorimotor cortex relay nuclei was significantly reduced in grafted enriched rats compared with nongrafted enriched rats. Afferent and efferent graft-host connections were identified in both grafted groups. Graft volumes did not differ.

Conclusions
Neural grafting enhanced functional outcome and reduced thalamic atrophy only when combined with housing in enriched environments.