bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence from comparative investigations that impaired platelet activation is not specific for stroke-prone spontaneously hypertensive rats.
Authors: Klee A , Vater S , Schmid-Schönbein G W , Seiffge D
Published: June 2011

Platelet behavior of Sprague Dawley (SD), Wistar (WI), Wistar-Kyoto (WKY), spontaneously hypertensive (SHR), and stroke-prone spontaneously hypertensive rats (SHRSP) was studied in vivo to evaluate the importance of hypertension-related hemostatic disorders.

The study was based on the model of stimulus-induced pulmonary microembolization of labeled platelets. After injection of 51Cr-labeled homologous platelets into urethane-anesthetized rats, the organ distribution of the platelets was continuously monitored by gamma detectors. Count rates of two detectors--one placed above the animals' thoraxes (C1), the other above their abdomens (C2)-and the ratio of C1:C2 were calculated. The following platelet activators were applied intravenously: adenosine diphosphate (ADP; 50 micrograms/kg), collagen (100 micrograms/kg), and thrombin (50 IU/kg).

All three substances caused a reversible pulmonary accumulation of the labeled platelets and hence an increase in C1/C2 (delta C1/C2%). ADP induced a shift of 75% in SD, 52% in WI, 32% in WKY, 30% in SHR, and 31% in SHRSP. Thrombin-mediated shift was 79% in SD, 64% in WI, 58% in WKY, 48% in SHR, and 54% in SHRSP. Collagen induced a shift of 85% in SD, 96% in WI, 84% in WKY, 56% in SHR, and 62% in SHRSP.

Because indistinguishable results were observed in both hypertensive strains, we conclude that impaired platelet aggregation is not specific for SHRSP. Hence, it may not primarily be responsible for the increased occurrence of stroke in these animals.
Improved posthypoxic recovery of synaptic transmission in gerbil neocortical slices treated with a calpain inhibitor.
Authors: Hiramatsu K , Kassell N F , Lee K S
Published: June 2011

Among the various calcium-induced biologic events occurring in hypoxic neurons, activation of the calcium-activated neutral proteinase (calpain) is a likely mediator of neuronal degeneration. In this study, we assessed the protective effects of a calpain inhibitor (Cbz-Val-Phe-H) against hypoxic damage to the neocortex.

An in vitro neocortical slice model from gerbils was used to study the delay to hypoxic depolarization during hypoxia and the recovery of synaptic responses after hypoxia. These responses were examined in control slices and slices treated with Cbz-Val-Phe-H.

The delay to hypoxic depolarization did not differ between treated and control groups. In contrast, synaptic recovery after a fixed period of hypoxia (15 minutes) was significantly improved in the Cbz-Val-Phe-H-treated slices (P < .01). Concentrations of Cbz-Val-Phe-H of 50 mumol/L or greater were significantly more protective than a concentration of 20 mumol/L (P < .01).

The data indicate that calcium-activated proteolysis plays a critical role in hypoxic damage to the neocortex and that calpain inhibitors may be useful therapeutic agents.
Subarachnoid blood causes pial arteriolar constriction in newborn pigs.
Authors: Parfenova H , Shibata M , Leffler C W
Published: June 2011

The present study was designed to determine in newborn animals the delayed effect of subarachnoid blood on pial arteriolar diameter and eicosanoid concentrations in cortical periarachnoid fluid.

Forty-eight to 96 hours after subarachnoid blood installation, closed cranial windows were implanted over the cerebral area exposed to blood in anesthetized, artificially ventilated newborn piglets. All pial arterioles greater than 60 microns in diameter were measured, and cortical periarachnoid fluid was collected for the determination of eicosanoids.

Subarachnoid blood resulted in a 20% to 30% decrease in the average diameter of pial arterioles exposed to blood for 48 to 96 hours, a decreased number of large pial arterioles (greater than 200 microns), and an increased number of small arterioles (60 to 100 microns). No changes in dilator prostanoids (prostacyclin [as 6-keto-prostaglandin F1 alpha] and prostaglandin E2) were detected. Concentrations of vasoconstrictor prostanoids in cortical cerebrospinal fluid increased. Thromboxane B2 increased to 430 +/- 70 pg/mL, and prostaglandin F2 alpha increased to 1370 +/- 180 pg/mL compared with 250 +/- 20 and 860 +/- 70 pg/mL, respectively, in the control group. The concentration of peptidoleukotrienes increased to 400 to 600 pg/mL 72 to 96 hours after blood installation, while the level in the control group was less than 80 pg/mL.

The altered balance between vasodilator and vasoconstrictor eicosanoids could contribute to cerebral vasoconstriction after subarachnoid blood installation in newborn pigs.
Interleukin-1 beta mRNA expression in ischemic rat cortex.
Authors: Liu T , McDonnell P C , Young P R , White R F , Siren A L , Hallenbeck J M , Barone F C , Feurestein G Z
Published: June 2011

Interleukin-1 beta is a proinflammatory cytokine produced by blood-borne and resident brain inflammatory cells. The present study was conducted to determine if interleukin-1 beta mRNA was produced in the brain of rats subjected to permanent focal ischemia.

Rat interleukin-1 beta cDNA, synthesized from stimulated rat peritoneal macrophage RNA by reverse transcription and polymerase chain reaction and cloned in plasmid Bluescript KS+, was used to evaluate the expression of interleukin-1 beta mRNA in cerebral cortex from spontaneously hypertensive rats and normotensive rats subjected to permanent middle cerebral artery occlusion. Interleukin-1 beta mRNA was quantified by Northern blot analysis and compared with rat macrophage RNA standard. To correct for gel loading, blots were also analyzed with cyclophilin cDNA, which encodes an abundant, conserved protein that was unchanged by the experimental conditions.

Interleukin-1 beta mRNA produced in the ischemic zone was significantly increased from 6 hours to 120 hours, with a maximum of 211 +/- 24% of interleukin-1 beta reference standard, ie, 0.2 ng stimulated rat macrophage RNA, mRNA compared with the level in nonischemic cortices (4 +/- 2%) at 12 hours after ischemia (P < .01; n = 6). Interleukin-1 beta mRNA at 12 hours after ischemia was markedly elevated in hypertensive rats over levels found in two normotensive rat strains. Neurological deficits were also apparent only in the hypertensive rats.

Brain interleukin-1 beta mRNA is elevated acutely after permanent focal ischemia and especially in hypertensive rats. These data suggest that this potent proinflammatory and procoagulant cytokine might have a role in brain damage following ischemia.
Interobserver reliability of a clinical classification of acute cerebral infarction.
Authors: Lindley R I , Warlow C P , Wardlaw J M , Dennis M S , Slattery J , Sandercock P A
Published: June 2011

The Oxfordshire Community Stroke Project (OCSP) clinical classification of subtypes of cerebral infarction (total and partial anterior circulation infarction, lacunar infarction, and posterior circulation infarction) can be used to predict early mortality, functional outcome, and whether the infarct was likely due to large- or small-vessel occlusion. The OCSP classification was originally developed and tested by neurologists as part of a community-based study of first-ever stroke, in which some cases were seen after the acute phase. We examined the interobserver reliability of the classification when used in everyday clinical practice in patients seen during the acute phase of stroke shortly after admission to the hospital.

Two clinicians independently assessed consecutive patients admitted to the hospital with an acute stroke and recorded both the neurological features and their opinion of the subtype of infarct.

Eighty-five patients were assessed. Interobserver agreement for the classification was moderate to good (kappa = 0.54; 95% confidence interval, 0.39 to 0.68). Differences in the assessment of the commonly elicited neurological signs explained many of the disagreements: interobserver agreement was good for some signs (hemiparesis [kappa = 0.77], dysphasia [kappa = 0.70]), moderate for some (hemianopia [kappa = 0.39]), and poor for others (sensory loss [kappa = 0.15]).

The classification was simple and practicable (and could be widely used in routine clinical practice, randomized controlled trials, and audit), and interobserver reliability was satisfactory.
Factors associated with early presentation of acute stroke.
Authors: Feldmann E , Gordon N , Brooks J M , Brass L M , Fayad P B , Sawaya K L , Nazareno F , Levine S R
Published: June 2011

Patients with stroke symptoms commonly delay many hours before seeking medical attention. We sought to explore the factors associated with early presentation of stroke patients to physicians.

We prospectively studied 100 consecutive acute stroke patients presenting to three large, urban medical centers. Using a standardized, structured interview and chart review, we assessed patient education about stroke, risk factors, clinical features of the stroke, source of stroke recognition, and timing of presentation. We did not study the distance from the site of stroke onset to the site of physician contact.

Stroke onset time was known in 96 of the patients. Mean patient age was 71.3 years, 79% had at least one stroke risk factor, 26% had prior transient ischemic attack, 19% had prior stroke, 74% had some high school education, and 86% had regular physicians. Only 8% had been previously educated about stroke symptoms. Eighty one percent of strokes were ischemic. The mean time to physician contact was 13.4 +/- 2.3 hours (median, 4.0 hours) and to neurologist contact was 21.2 +/- 2.9 hours. A skewed distribution of presentation times accounts for the mean-median differences. A small number of patients presenting very late could have an effect on the correlations between presentation time and the variables studied. Early presentation time was associated with increased age, the sudden onset of a stable deficit, and recognition that the symptoms signified stroke. Only the sudden onset of a stable deficit correlated independently with early presentation time (P = .0048). There was no correlation between presentation time and prior transient ischemic attack or stroke, headache, vomiting, loss of consciousness or seizures at onset, or stroke subtype, but a type II error could not be excluded.

Despite their education level, regular health care, and risk factors, especially prior stroke and transient ischemic attack, these patients were not knowledgeable about stroke and delayed many hours before contacting physicians. The course of symptoms and recognition that they signified stroke were associated with earlier presentation. Patient education focused on groups at risk may hasten the presentation and treatment of acute stroke.
Lacunar infarcts and white matter attenuation. Ophthalmologic and microcirculatory aspects of the pathophysiology.
Authors: Schneider R , Rademacher M , Wolf S
Published: June 2011

By means of neurological and ophthalmologic examinations we considered whether there is a microcirculatory disorder not related to hypertension and diabetes in patients with lacunar infarcts and whether there are microcirculatory differences in patients with lacunar infarcts compared with those with white matter attenuation.

Eighty neurological patients with a lacunar infarct underwent computed tomography and, based on the results, were prospectively assigned to subgroups as follows: (1) patients without changes; (2) patients with white matter attenuation but without lacunar infarcts; (3) patients with lacunar infarcts alone; and (4) patients with both lacunar infarcts and white matter attenuation. Clinical and ophthalmologic parameters were monitored. The retinal microcirculation was studied by videofluorescence angiography. These neurological patients were compared with control ophthalmologic patients matched for age, sex, hypertensive and diabetic ocular fundus changes, and smoking habits.

On average, the 80 patients with lacunar infarcts had a significantly (P = .0001) slower arteriovenous passage time (2.6 +/- 0.7 seconds) than the ophthalmologic control subjects (1.6 +/- 0.6 seconds). Arteriovenous dye passage time through the retinal microcirculation was nearly normal (2.2 +/- 0.8 seconds) in patients with white matter attenuation alone, but was significantly prolonged in patients with lacunar infarcts (2.9 +/- 0.8 seconds, P = .00085) or both white matter attenuation and lacunar infarcts (2.8 +/- 0.4 seconds, P = .008).

Patients with lacunar infarcts are characterized by an additional disorder of retinal microcirculation independent of arterial hypertension and diabetes. Our data suggested that white matter attenuation and lacunar infarcts may be phenomena with only weak interdependence.
Ultrasound findings in spontaneous extracranial vertebral artery dissection.
Authors: Sturzenegger M , Mattle H P , Rivoir A , Rihs F , Schmid C
Published: June 2011

In this study we analyzed the value of ultrasound examination for diagnosis of vertebral artery dissection.

The vertebrobasilar arterial system was assessed in 14 patients using transcranial and extracranial pulsed-wave Doppler and duplex sonography.

The dissections were verified by angiography (in 1 patient), magnetic resonance imaging (in 5), or both (in 8). The dissected segments were atlantoaxial (V-3) in 6, V-3 and intertransverse (V-2) in 3, V-3 and intracranial (V-4) in 3, and V-2 in 2 patients. Extracranial and transcranial Doppler examination of the atlas loop, involved in 12 patients, showed absent flow signal in 5, low bidirectional flow signal in 1, and poststenotic low blood flow velocities in 3 patients. Seven of these patients had high-grade stenosis or occlusion. The stenotic segment with increased flow signal could be identified directly in 2 patients. Duplex examination of the intertransverse segment confirmed absent flow in 4 patients, making technically insufficient examination unlikely. In the 2 patients with directly detected stenosis, duplex examination showed low flow velocities before the stenosis. The combined use of extracranial and transcranial Doppler and duplex sonography increases the diagnostic yield to detect vertebral artery pathology. If any abnormal sonographic finding was considered, the yield was 86%; relying only on definitively abnormal findings (absent flow signal, severely reduced vertebral artery blood flow velocities, no diastolic flow, bidirectional flow, and a stenosis signal), the yield was 64%.

In most cases, there is no pathognomonic ultrasound finding for vertebral artery dissection. However, if a patient presents with suggestive symptoms, ultrasound may corroborate the clinical suspicion and aid in the decision regarding early anticoagulant treatment. A definite diagnosis can be made noninvasively when magnetic resonance imaging demonstrates hematoma in the vessel wall. Angiography yields additional information such as nature of underlying vascular disease, site and extent of dissection, intracranial extension, and presence of pseudoaneurysm.
Nitric oxide and S-nitroso-L-cysteine as endothelium-derived relaxing factors from acetylcholine in cerebral vessels in cats.
Authors: Kukreja R C , Wei E P , Kontos H A , Bates J N
Published: June 2011

The predominant view is that the endothelium-derived relaxing factor generated by acetylcholine from blood vessels is nitric oxide. However, there is evidence suggesting that certain nitric oxide-containing compounds such as nitrosothiols resemble the endothelium-derived relaxing factor generated by acetylcholine more closely than does nitric oxide itself. Accordingly, we compared the effects of nitric oxide and S-nitroso-L-cysteine on cerebral arteriolar caliber in relation to the associated increments in nitrite concentration in the effluent.

Acetylcholine, nitric oxide, and S-nitroso-L-cysteine were administered by continuous superfusion in oxygen-free solution through the space under a cranial window in anesthetized cats. Nitrite concentration was measured in the effluent. The degree of vasodilation induced was evaluated in relation to the increment in nitrite concentration.

All agents induced dose-dependent vasodilation and dose-dependent increments in nitrite concentration in the effluent. For any given degree of vasodilation, the increments in nitrite concentration were equivalent during acetylcholine or S-nitroso-L-cysteine infusion, whereas the nitrite concentrations were 10 times higher during nitric oxide infusion. After administration of nitroarginine, a competitive inhibitor of nitric oxide synthesis from arginine, there was depression in the vasodilation as well as the increment in nitrite concentration induced by acetylcholine.

S-Nitroso-L-cysteine resembles endothelium-derived relaxing factor from acetylcholine more closely than does nitric oxide.
Effect of a novel thromboxane A2 receptor antagonist, S-1452, on postischemic brain injury in rats.
Authors: Matsuo Y , Izumiyama M , Onodera H , Kurosawa A , Kogure K
Published: June 2011

Arachidonate metabolites have been implicated in the development of cerebral injury after ischemia. Particular importance has been placed on the balance of thromboxane A2 and prostaglandin I2 because of its regulative activity on platelet functions and arterial tone. The purpose of the present study was to shed light on the role of thromboxane A2 in postischemic brain injury.

We evaluated the effects of S-1452, a novel thromboxane A2 receptor antagonist, on brain edema, infarct areas, and survival rate in rats with middle cerebral artery occlusion. A transient middle cerebral artery occlusion model was produced by inserting a piece of silicon-coated nylon thread into the internal carotid artery.

The ratio of plasma thromboxane B2 to 6-keto-prostaglandin F1 alpha significantly rose at 0 hour (P < .05), 1 hour (P < .01), 3 hours (P < .05), and 12 hours (P < .05) and then nearly returned to the normal level at 24 hours after reperfusion following 1-hour occlusion. Pretreatment with S-1452 (5, 10, or 50 mg/kg PO) significantly attenuated the increase in postischemic water content in the cerebral cortex perfused by the anterior cerebral artery and the cerebral cortex perfused by the middle cerebral artery in a dose-dependent manner but slightly attenuated it in the caudate putamen 24 hours after reperfusion following 1-hour occlusion. Pretreatment with S-1452 (10 mg/kg PO) also significantly decreased the areas of infarction in the front parts of the cerebrum. The survival rate of animals after 2 hours of occlusion tended to be improved by treatment with S-1452 (10 mg.kg-1.d-1 PO), although there was no statistical significance.

Our results suggest that thromboxane A2 is closely related to postischemic brain injury in the early phase of recirculation and that S-1452 may have a protective effect on postischemic brain injury.
Hemibody tremor related to stroke.
Authors: Dethy S , Luxen A , Bidaut L M , Goldman S
Published: June 2011

Hemibody tremor is an uncommon manifestation of stroke. We describe a case investigated by both brain magnetic resonance imaging and positron emission tomography using [18F]fluorodeoxyglucose.

Three months after a pure motor stroke, a 65-year-old man developed a right arm and leg tremor. The tremor was of large amplitude, intermittent at rest; its frequency was 5 to 6 Hz. Neither rigidity nor akinesia was detected, and administration of L-dopa was ineffective. Brain magnetic resonance imaging revealed an ischemic lesion in the left centrum semiovale and a left caudate lacunar infarction. We suspected that the resting unilateral tremor was related to this lacunar lesion. Positron emission tomography demonstrated glucose hypermetabolism in the left sensorimotor cortex.

This case suggests that unilateral tremor may be related to a lacunar stroke in the caudate nucleus and may be accompanied by an increased glucose metabolism in the contralateral sensorimotor cortex.
Recovery of functional status after stroke. A postrehabilitation follow-up study.
Authors: Ferrucci L , Bandinelli S , Guralnik J M , Lamponi M , Bertini C , Falchini M , Baroni A
Published: June 2011

Information on predictors of long-term change in functional capacity after a rehabilitation program in stroke patients is scant. This study describes the long-term evolution of self-reported functional ability after discharge from rehabilitation and its relation with age, level of neural impairment at discharge, and changes in neural impairment during follow-up.

Fifty patients (31 men and 19 women; mean +/- SD age, 66.0 +/- 9.9 years; range, 47-86 years) with a first unilateral stroke and no severe cognitive impairment were consecutively enrolled. Self-reported disability in activities of daily living and neural impairment measured by the Fugl-Meyer Scale were evaluated after discharge from a rehabilitation program and 3 and 6 months later.

Functional disability was significantly reduced after 3 and 6 months. Attenuation of disability occurred mainly among those patients with more severe baseline neural impairment. In this group, patients aged > or = 65 years were more disabled at baseline than younger individuals, but they had the same rate of improvement. In patients aged < 65 years, changes in disability over time could be attributed to changes in neural function, whereas older patients' functional recovery was greater than that expected from their improvement in neural impairment alone.

These results suggest that in stroke patients with severe neural damage further functional improvement occurs even after completion of a rehabilitation program. There is evidence that older patients may be more likely to employ compensatory strategies to overcome some of the neural impairment that remains after stroke.
Secular trend of mortality from cerebral infarction and cerebral hemorrhage in Taiwan, 1974-1988.
Authors: Chang C C , Chen C J
Published: June 2011

Pathological patterns of stroke are different in various races, with the predominant stroke type in the Chinese being intracerebral hemorrhage. A total of 31,078 deaths from cerebral infarction and 77,773 deaths from cerebral hemorrhage in Taiwan were reported for groups of subjects aged 40-79 years during the period 1974-1988 to elucidate their secular trends.

Vital statistics and demographic data were collected for analyzing the truncated age-adjusted mortality rates. Poisson regression analysis was used to estimate the relative risk and 95% confidence interval.

The mortality rates for cerebral hemorrhage were greater than those for cerebral infarction. The mortality rates increased exponentially with age for both subtypes. The decline in age-specific mortality for the period 1974-1983 was much more striking for cerebral hemorrhage than for cerebral infarction. Mortality from cerebral infarction and hemorrhage increased with age for all birth cohorts except the cerebral hemorrhage mortality of the oldest cohort. Male/female ratios for both cerebral infarction and hemorrhage were greater in the younger age groups. The cerebral hemorrhage/infarction ratio during the period 1984-1988 was highest for the younger age groups and lowest for the oldest age groups.

The different secular trends of mortality from cerebral infarction and hemorrhage imply that these two patterns of stroke may be associated with some different risk factors.
Increased thromboxane biosynthesis in patients with acute cerebral ischemia.
Authors: Koudstaal P J , Ciabattoni G , van Gijn J , Nieuwenhuis H K , de Groot P G , Sixma J J , Patrono C
Published: June 2011

Clinical and experimental studies suggest that platelets have a major role in the pathogenesis of cerebral ischemia. However, ex vivo both platelet aggregation studies and measurements of platelet-derived products in patients with cerebral ischemia have shown inconsistent results. The present study was designed to resolve this inconsistency.

We have measured the urinary excretion of a thromboxane metabolite, 11-dehydro-thromboxane B2, by a previously validated radioimmunoassay technique in 51 patients with acute cerebral ischemia who had experienced either a transient ischemic attack (14 patients) or an ischemic stroke (37 patients) and in 20 control patients with nonvascular neurological disorders. The median time between the onset of symptoms and urine sampling was 24 hours (range, from 2 hours to 8 days).

The excretion rate of immunoreactive 11-dehydro-thromboxane B2 ranged between 39 and 478 pmol/mmol creatinine in patients with a transient ischemic attack and between 23 and 5,916 pmol/mmol creatinine in stroke patients, with 29% (p = 0.18) and 51% (p = 0.004) of the urine samples, respectively, exceeding the upper limit of the control samples (251 pmol/mmol creatinine [mean +/- 2 SD]) (p = 0.01). In stroke patients, metabolite excretion was not related to the type (cortical or "lacunar") or site of cerebral infarction. Low-dose aspirin (50 mg per day for 7 days) reduced the urinary excretion by approximately 85% in 11 consecutive stroke patients.

We conclude that 1) episodes of enhanced thromboxane biosynthesis are detected infrequently in patients with a transient ischemic attack, 2) aspirin-suppressible episodes of increased thromboxane formation can be detected during the early phase of acute ischemic stroke, and 3) this finding may provide a rationale for testing the efficacy and safety of this drug in this setting.
Excitotoxicity affects membrane potential and calmodulin kinase II activity in cultured rat cortical neurons.
Authors: Churn S B , Sombati S , Taft W C , DeLorenzo R J
Published: June 2011

Glutamate-induced excitotoxicity has been implicated as a causative factor for selective neuronal loss in ischemia and hypoxia. Toxic exposure of neurons to glutamate results in an extended neuronal depolarization that precedes delayed neuronal death. Because both delayed neuronal death and extended neuronal depolarization are dependent on calcium, we examined the effect of glutamate exposure on extended neuronal depolarization and calcium/calmodulin-dependent protein kinase II (CaM kinase II) activity.

Three-week-old cortical cell cultures from embryonic rats were exposed to 500 microM glutamate and 10 microM glycine or to control medium for 10 minutes. Cells were examined for neuronal toxicity, electrophysiology, and biochemical alterations. In one set of experiments, whole-cell current clamp recording was performed throughout the experiment. In a parallel experiment, cortical cultures were allowed to recover from glutamate exposure for 1 hour, at which time the cells were homogenized and CaM kinase II activity was assayed using standard techniques.

Excitotoxic exposure to glutamate resulted in extended neuronal depolarization, which remained after removal of the glutamate. Glutamate exposure also resulted in delayed neuronal death, which was preceded by significant inhibition of CaM kinase II activity. The excitotoxic inhibition of CaM kinase II correlated with neuronal loss, was N-methyl-D-aspartate receptor-mediated, and was not due to autophosphorylation of the enzyme.

Glutamate-induced delayed neuronal toxicity correlates with extended neuronal depolarization and inhibition of CaM kinase II activity. Because inhibition of CaM kinase II activity significantly preceded the histological loss of neurons, the data suggest that modulation of CaM kinase II activity may be involved in the cascade of events resulting in loss of calcium homeostasis and delayed neuronal death.
Possible association of ischemic stroke with phentermine.
Authors: Kokkinos J , Levine S R
Published: June 2011

Some commonly used anorexiants, including methamphetamine and phenylpropanolamine, have been associated with stroke. Because phentermine is an anorexiant with a chemical structure similar to that of amphetamines, similar side effects might be expected.

Two patients using phentermine (one was also using phendimetrazine) developed ischemic cerebrovascular disease. One suffered a cerebral infarct with angiographic evidence of vasculopathy involving multiple vascular beds. The other patient developed headache and a hemisensory disturbance of 7 days' duration.

Phentermine, and possibly phendimetrazine, should be considered an anorexiant and sympathomimetic drug that can be associated with ischemic cerebrovascular disease.
Carotid artery intraplaque hemorrhage and stenotic velocity.
Authors: Beach K W , Hatsukami T , Detmer P R , Primozich J F , Ferguson M S , Gordon D , Alpers C E , Burns D H , Thackray B D , Strandness D E
Published: June 2011

One of the proposed mechanisms for sudden expansion of a carotid bifurcation plaque is hemorrhage within the lesion. It has been postulated that the sudden increase in plaque size will acutely reduce blood flow to the ipsilateral hemisphere and induce either a transient ischemic attack or a stroke. In this study, the relation between peak systolic velocity at the site of narrowing and its potential role in the development of intraplaque hemorrhage were investigated.

Ten patients who had carotid endarterectomy were examined by duplex Doppler sonography before surgery to determine the peak systolic velocity at the site of maximal narrowing. The excised carotid plaques were sectioned at 1-mm intervals and examined for histological evidence of intraplaque hemorrhage. The recorded peak systolic velocities in patients with intraplaque hemorrhage were compared with the velocities in cases in which no hemorrhage was identified.

Five of the ten patients had intraplaque hemorrhage. Four of the five patients with intraplaque hemorrhage had a peak systolic velocity of > 420 cm/sec and diastolic velocities of > 160 cm/sec; none of the patients without intraplaque hemorrhage had such high values.

Peak systolic velocity is significantly higher in patients with intraplaque hemorrhage. The specificity and sensitivity of a peak systolic velocity of > 420 cm/sec in predicting intraplaque hemorrhage remains to be determined.
Hemodynamic and metabolic effects of flunarizine in experimental subarachnoid hemorrhage in dogs.
Authors: De Ley G , Eechaute W , Strijckmans K , Goethals P , Lemahieu I , Van de Velde E , Weyne J
Published: June 2011

Cerebral blood flow and oxygen metabolism were measured and a cerebral angiography was performed in dogs with experimental subarachnoid hemorrhage to assess the relation between arterial narrowing (vasospasm) and the fall of blood flow. Cerebral blood volume and the cerebrovascular CO2 reactivity were also measured to estimate the cerebrovascular reserve. Several groups of dogs were treated with flunarizine in different regimens to assess its possible therapeutic effect.

The experiments were performed in the three-hemorrhage canine model for subarachnoid hemorrhage. Cerebral blood flow and cerebral oxygen metabolism were measured in anesthetized (nitrous oxide) dogs using positron emission tomography in combination with the 15O steady-state method. Basilar artery diameter was evaluated by digital subtraction angiography.

In normal dogs, cerebral blood flow, oxygen consumption, and oxygen extraction ratio were 46.4 +/- 9.0 ml/100 ml per minute, 3.65 +/- 0.76 ml/100 ml per minute, and 39.9 +/- 3.4%, respectively; basilar artery diameter was 1.33 +/- 0.25 mm. Repeated subarachnoid blood injection (3 x 5 ml) reduced basilar artery diameter to < 20% of normal (p < 0.01). Cerebral blood flow was reduced by only 25% (p < 0.001); oxygen consumption was preserved at a low normal level by a 29% compensatory increase of the oxygen extraction (p < 0.001). Cerebral blood volume and cerebrovascular CO2 reactivity remained nearly normal. Early (after the first blood injection) peroral treatment with flunarizine (0.5 mg/kg daily) resulted in less severe basilar artery narrowing (56% of normal; p < 0.05 versus untreated). However, this treatment had no effect on cerebral blood flow, blood volume, oxygen consumption, and extraction.

The observed fall of cerebral blood flow in experimental subarachnoid hemorrhage is not related to arterial narrowing but to an increased cerebrovascular resistance at the level of the small parenchymal vessels, and the latter, in contrast to arterial narrowing, is unaffected by flunarizine.
Hydroxyl radical-dependent inactivation of guanylate cyclase in cerebral arterioles by methylene blue and by LY83583.
Authors: Kontos H A , Wei E P
Published: June 2011

Methylene blue and 6-anilino,5,8-quinolinedione (LY83583) are used extensively to block activation of guanylate cyclase. Both agents generate oxygen radicals. Therefore, it appeared profitable to investigate whether the generation of oxygen radicals by these agents is responsible for the blockade of responses to nitrodilators that act via activation of guanylate cyclase to relax vascular smooth muscle and cause vasodilation.

We tested in anesthetized cats equipped with cranial windows responses to topical application of nitroglycerin, nitroprusside, and adenosine before and during topical application of methylene blue (5 microM). Responses to the vasoactive agents were tested during application of methylene blue after permeabilization of the cell membrane with a detergent to allow methylene blue to enter vascular smooth muscle. Responses were also tested in the presence of superoxide dismutase, catalase, deferoxamine, or dimethyl sulfoxide to scavenge reactive products of oxygen metabolism or to eliminate catalytic iron. In additional experiments we tested the effects of topical application of nitroprusside or adenosine before and after application of LY83583. The responses to the vasoactive agents were also tested in the presence of superoxide dismutase, catalase, or dimethyl sulfoxide in addition to LY83583. We also tested responses to calcitonin gene-related peptide before and in the presence of LY83583 with or without superoxide dismutase.

Methylene blue eliminated the arteriolar dilation in response to nitroprusside and nitroglycerin after permeabilization of the cell membrane with a detergent but not before. The responses to adenosine were unaffected. The blockade induced by methylene blue was reversed by superoxide dismutase, catalase, or dimethyl sulfoxide but not by deferoxamine. LY83583 blocked responses to nitroprusside but not to adenosine. The blockade was eliminated by superoxide dismutase, catalase, or dimethyl sulfoxide. LY83583 blocked the vasodilation induced by calcitonin gene-related peptide. This blockade was reversed by superoxide dismutase.

Methylene blue and LY83583 prevent the activation of soluble guanylate cyclase by nitrodilators or by calcitonin gene-related peptide by generating oxygen radicals. The mediator of this response is the hydroxyl radical. Methylene blue does not enter the vascular smooth muscle of cerebral arterioles unless the cell membrane is permeabilized.
Brain pHi, cerebral blood flow, and NADH fluorescence during severe incomplete global ischemia in rabbits.
Authors: Tomlinson F H , Anderson R E , Meyer F B
Published: June 2011

The aim of this experiment was to study the serial changes in brain intracellular pH, cerebral blood flow, and the oxidation/reduction level of intramitochondrial nicotinamide adenine dinucleotide fluorescence across the cortical surface during severe incomplete global ischemia.

Reduced nicotinamide adenine dinucleotide fluorescence and brain intracellular pH using the pH-sensitive indicator umbelliferone were measured with in vivo panoramic fluorescence imaging of the cortical surface. Cerebral blood flow was measured with the clearance of both umbelliferone and xenon-133. Fifteen minutes of severe incomplete global ischemia was produced by temporary occlusion of the innominate, left carotid, and subclavian arteries in five fasted New Zealand White rabbits.

Baseline brain intracellular pH was homogeneous over the exposed cortex, measuring 7.00 +/- 0.02, while cerebral blood flow was 48.0 +/- 2.6 ml/100 g/min. During 15 minutes of ischemia, cerebral blood flow measured 6.3 +/- 1.8 ml/100 g/min and brain pH declined to 6.61 +/- 0.02 (p < 0.005); in addition, there were acidotic foci with pH measuring 6.40 +/- 0.10. During reperfusion, there was an initial normalization of brain intracellular pH without an alkaline shift followed by a recurrent cortical acidosis of pH 6.88 +/- 0.06. There was a heterogeneous pattern of fluorescence that increased significantly following 60 minutes of reperfusion, coinciding with a postischemic hypoperfusion. The hypoperfusion was a uniform reduction in cerebral blood flow over the brain's surface, with reductions of 42.5% and 44.2% at 30 and 45 minutes, respectively.

During incomplete global ischemia there is a heterogeneous pattern of brain intracellular pH and reduced nicotinamide adenine dinucleotide changes that do not correlate with changes in cortical blood flow. The acidotic foci that were approximately 0.2 pH units more acidotic than the surrounding cortex may be the result of continued glucose delivery under anaerobic conditions. The degree of reduced nicotinamide adenine dinucleotide fluorescence suggests that the cortex is most vulnerable to metabolic failure after 60 minutes of reperfusion following severe incomplete global ischemia. The heterogeneous pattern of brain intracellular pH and reduced nicotinamide adenine dinucleotide changes suggest that there may be a selective vulnerability of cortical tissue to an ischemic challenge.
Fulminant cerebral infarctions with membranous nephropathy.
Authors: Chaturvedi S
Published: June 2011

Arterial thromboses, including cerebral infarction, are a rare complication of the nephrotic syndrome.

A 37-year-old woman presented with right upper extremity ischemia, left middle cerebral artery thrombosis, and right cerebellar infarction. She quickly herniated, and postmortem evaluation revealed membranous nephropathy. Increased fibrinogen and decreased free protein S levels were noted.

Membranous nephropathy can lead to rapidly progressive cerebral infarctions, with possible fatality. There is not a unifying hematologic explanation for the strokes seen with nephrotic syndrome.
Evidence for embolization from a posterior cerebral artery thrombus by transcranial Doppler monitoring.
Authors: Diehl R R , Sliwka U , Rautenberg W , Schwartz A
Published: June 2011

Transcranial Doppler monitoring enables the detection of emboli passing through intracranial arteries. Comparison of the different intracranial vessels with respect to emboli detection can be of use in identifying the source of embolism.

We report the case of a patient with an acute posterior cerebral artery (PCA) infarct on the right side, with evidence for high-degree ipsilateral PCA narrowing on admission. During transcranial Doppler monitoring 3 days later, we found frequent emboli-like signals in the power spectrum of the right PCA distal to the stenosis but not in any other intracranial vessels. Four days later, angiography and transcranial Doppler failed to show PCA narrowing, and transcranial Doppler monitoring of the right PCA showed no further emboli-like signals. A stenosis of the right vertebral artery was regarded as the possible source of thromboembolic narrowing of the PCA.

We assume that in our patient a thrombotic clot in the PCA was resolved autolytically through detachment of small emboli into the distal part of the PCA. We speculate that in the early course of autolysis a larger fragment of the clot had occluded one of the distal branches, thus leading to the small PCA territory infarct.
Current role of electroencephalography in cerebral ischemia.
Authors: Faught E
Published: June 2011

The electroencephalogram has been largely supplanted by neuroimaging techniques for the diagnosis and localization of ischemic stroke. However, because of its close correlation with cerebral metabolism and its ability to detect brief transient alterations in cortical function, the electroencephalogram may still be useful for certain diagnostic applications in stroke.

The relation of electroencephalographic phenomena to cerebral blood flow and metabolism is reviewed. Ten clinical questions that can be addressed by the electroencephalogram in patients with stroke are posed. The presence of seizures, confirmation of diagnosis, intraoperative monitoring, and level of consciousness are areas of proven usefulness. The electroencephalogram provides less worthwhile information about the time course, prognosis, and localization of strokes. Computerized techniques are of potential but unproven value.

The electroencephalogram retains a worthwhile place in the evaluation of patients with cerebral ischemia when it is used to answer specific questions. All patients with strokes do not need electroencephalograms, but the test can provide uniquely useful data in some.
Intracellular pH during reperfusion influences evoked potential recovery after complete cerebral ischemia.
Authors: Maruki Y , Koehler R C , Eleff S M , Traystman R J
Published: June 2011

Increasing ischemic duration delays recovery of intracellular pH and depresses recovery of somatosensory evoked potentials. We tested whether manipulation of the rate of pH recovery influences evoked potential recovery after complete ischemia.

Four groups of eight anesthetized dogs underwent 12 minutes of complete ischemia followed by 4 hours of reperfusion with either 1) normocapnia, 2) normocapnia and acetazolamide (25 mg/kg at reperfusion plus 12.5 mg/kg per hour, 3) hypocapnia, or 4) hypercapnia. Intracellular pH was measured by phosphorus magnetic resonance spectroscopy, and intracellular bicarbonate was calculated using sagittal sinus partial pressure of CO2 during reperfusion.

In the normocapnic control group, intracellular pH decreased from 7.10 +/- 0.04 (+/- SEM) to 6.13 +/- 0.08 during ischemia and recovered to 6.90 +/- 0.08 by 30 minutes of reperfusion. Bicarbonate also largely recovered (9.9 +/- 1.6 mM). With acetazolamide pH (6.51 +/- 0.10) and estimated bicarbonate (4.8 +/- 1.3 mM) remained depressed at 30 minutes and did not fully recover until 60-75 minutes. However, percent recovery of somatosensory evoked potential amplitude at 4 hours of reperfusion was less with acetazolamide (23 +/- 4%) than in the control group (52 +/- 5%). With hypercapnic reperfusion, which delayed pH recovery but not bicarbonate recovery, evoked potential recovery was also depressed (27 +/- 5%). With hypocapnic reperfusion, which delayed bicarbonate recovery but not pH recovery, evoked potential recovery (52 +/- 6%) was not depressed compared with controls. Recovery of adenosine triphosphate and oxygen consumption was similar among groups.

Delayed recovery of intracellular pH with or without delayed recovery of bicarbonate during reperfusion further impairs somatosensory evoked potential recovery independent of recovery of high-energy phosphates. Persistence of acidosis during reperfusion can contribute to postischemic electrophysiological deficit.
Effects of dimethylthiourea on selective neuronal vulnerability in forebrain ischemia in rats.
Authors: Pahlmark K , Folbergrová J , Smith M L , Siesjö B K
Published: June 2011

Attempts have been made to characterize conditions under which oxygen free radicals contribute to ischemic brain damage. According to one hypothesis, free radicals are likely mediators of damage only when ischemia is of such long duration that infarction develops or when either preischemic hyperglycemia or hyperthermia is present. The objective of the present study was to explore whether 15 minutes of forebrain ischemia, an insult that leads to selective neuronal vulnerability but not to infarction, is accompanied by production of pathogenetically important free radicals.

Using a histopathological end point, we studied amelioration of damage by a free radical scavenger, dimethylthiourea, administered in a dose of 750 mg/kg i.p. 60 minutes before ischemia. To study whether this insult leads to detectable protein oxidation we assessed the activity of glutamine synthetase and of carbonyl compounds in the soluble protein fraction.

In control animals, the transient ischemia resulted in the expected damage to vulnerable neurons in hippocampus, caudoputamen, and neocortex after 7 days of recovery. Glutamine synthetase activity in caudoputamen and hippocampus and carbonyl content in the soluble protein fraction after 90 minutes of recovery were not affected. However, dimethylthiourea significantly reduced damage to hippocampus and caudoputamen (p < 0.001) and neocortex (p < 0.005).

Lack of evidence of protein oxidation supports the notion that 15 minutes of forebrain ischemia results in a limited insult, confined to the neurons. Provided that unspecific effects can be excluded, the results obtained with dimethylthiourea suggest that free radicals contribute to selective neuronal necrosis.
Acute ischemic stroke from fibrocartilaginous embolism to the middle cerebral artery.
Authors: Toro-González G , Navarro-Román L , Román G C , Cantillo J , Serrano B , Herrera M , Vergara I
Published: June 2011

Fibrocartilaginous embolism from the nucleus pulposus has been reported as a rare cause of spinal cord ischemia. We were unable to find previous reports of embolism from this source to cerebral arteries.

A previously healthy 17-year-old girl fell during a basketball game. Left hemiparesis and unresponsiveness developed followed by signs of right uncal herniation and death over a 3-day period. There was no evidence of neck, head, or spine trauma, and cardiac evaluation was normal. Neuropathological examination showed extensive ischemic infarction of the right middle cerebral artery territory, brain edema, and herniation. Complete embolic occlusion of the right middle cerebral artery by fibrocartilaginous material, consistent with nucleus pulposus, was documented. Small, terminal coronary artery branches also showed embolism by the same material and limited areas of myocardial infarction.

Acute cerebral embolism after minor trauma in a young patient may be rarely due to fibrocartilaginous embolism from the nucleus pulposus. The pathogenesis of this problem remains poorly understood, but systemic embolism appeared to have occurred in this case.
Denial of illness in stroke.
Authors: Ellis S J , Small M
Published: June 2011

The effects of stroke on classically nondominant hemisphere functions have received less attention than those on the dominant hemisphere, but visuospatial neglect and denial of illness both produce significant morbidity.

The early literature on denial of illness is discussed and the etiological theories are examined. These are explanations based on deficits of higher mental function, impaired sensory input (especially proprioceptive), an abnormal representation of body image, psychodynamic defense mechanisms, and/or premorbid personality factors.

Denial of illness is an important consequence of stroke. No explanation thus far proposed is entirely satisfactory. The consequences on rehabilitation and strategies for therapy have not been adequately investigated.