bluuebunny/crossref_metadata_2025 huggingface dataset:
Paraplegia following thoracic aortic cross-clamping in dogs. No difference in neurological outcome with a barbiturate versus isoflurane.
Authors: Mutch W A , Graham M R , Halliday W C , Teskey J M , Thomson I R
Published: June 2011

We compared the incidence and severity of paraplegia following thoracic aortic cross-clamping in dogs for two anesthetic regimens. Animals were randomly assigned to receive methohexital (group M; n = 9) or isoflurane (group I; n = 9). We expected a better neurological outcome in animals administered methohexital because of superior neuronal protection and greater spinal cord perfusion pressure (mean arterial pressure below the cross-clamp site minus mean cerebrospinal fluid pressure).

After surgical preparation and a 30-minute stabilization period, dogs in group M received 14 +/- 6 mg.kg-1 i.v. methohexital to induce an isoelectric electroencephalogram followed by a continuous infusion of methohexital at 20 mg.kg-1 x h-1. Dogs in group I received 1.4 +/- 0.2% end-tidal isoflurane (1 minimum alveolar concentration). The thoracic aorta was then occluded 2.5 cm distal to the left subclavian artery for 30 minutes and then released. Hemodynamics and cerebrospinal fluid pressure were measured at (1) baseline, (2) 2 minutes after aortic cross-clamping, (3) 20 minutes after aortic cross-clamping, (4) 5 minutes after aortic unclamping, and (5) 30 minutes after resuscitation. At 24 hours a neurological assessment was performed. After the clinical assessment the dogs were killed and the spinal cord removed immediately for histopathologic study.

There were no differences in nasopharyngeal temperature, PaCO2, pH, or hemoglobin at any time between groups. With cross-clamping, the spinal cord perfusion pressure decreased precipitously. However, there was no difference in spinal cord perfusion pressure between groups at any time (P = .5555). The neurological outcome, assessed at 24 hours after thoracic aortic cross-clamping by a veterinarian unaware of the anesthetic protocol, was not different between groups (P > .5, two-tailed Mann-Whitney rank-sums test). When anesthetized with methohexital 5 of 9 dogs were paraplegic; with isoflurane 7 of 9 dogs were paraplegic. By Spearman's rank test, a strong inverse correlation between the Tarlov score and the ratio of dead to total lumbar anterior spinal cord neurons was seen (Spearman's correlation coefficient = -.8358; P = .0001).

We conclude that no advantage was offered by the choice of anesthesia to neurological outcome after 30 minutes of thoracic aortic cross-clamping in this canine model.
Apathy following cerebrovascular lesions.
Authors: Starkstein S E , Fedoroff J P , Price T R , Leiguarda R , Robinson R G
Published: June 2011

Although apathy has been reported to constitute a frequent sequela of stroke lesions, there have been no prospective studies on the frequency and correlates of apathy after stroke lesions. In the present study, we examined the frequency and correlates of apathy in a consecutive series of 80 patients with cerebrovascular lesions.

We included patients within the first 10 days after a stroke lesion. Patients were examined with a comprehensive neuropsychiatric battery that included the Apathy Scale.

Eighteen patients (22.5%) showed apathy, nine of whom were also depressed. On the other hand, 18 patients (22.5%) showed depression in the absence of apathy. Although depression and apathy may exist independent of one another, major depression (but not minor depression) was associated with an increased frequency of apathy. Apathy was also significantly associated with older age, cognitive impairments, and deficits in activities of daily living. Finally, apathy was significantly associated with lesions in the posterior limb of the internal capsule.

These findings demonstrate that apathy is a frequent finding among patients with acute stroke lesions and may coexist with important emotional and cognitive poststroke disturbances.
The impact of cardiac index on cerebral hemodynamics.
Authors: Saha M , Muppala M R , Castaldo J E , Gee W , Reed J F , Morris D L
Published: June 2011

Current noninvasive testing allows accurate assessment of cerebrovascular hemodynamics. The cardiovascular influence on the noninvasive assessment of cerebrovascular studies has not been defined. This study was designed to determine the effect of cardiac index (CI) on cerebral blood flow velocities, ocular pulse amplitude, ophthalmic systolic pressure, and ocular blood flow (OBF) as currently estimated by noninvasive laboratories.

Based on a retrospective study of 181 patients, we prospectively evaluated 45 patients undergoing right heart catheterization for hemodynamic monitoring to correlate the relation between CI, transcranial Doppler sonography, and ocular pneumoplethysmography. Patients with hemodynamic instability, severe carotid stenoses, massive cerebral infarct, or sepsis were ineligible for the study. Simultaneous recordings of systemic blood pressure, ophthalmic systolic pressure, heart rate, ocular pulse amplitude, middle cerebral artery blood flow velocities, and cardiac output were obtained on all patients. OBF was calculated from the heart rate and ocular pulse amplitude.

The relation between OBF and CI is expressed by the equation CI = 2.36 + 0.61 x OBF (r = .47, P = .0010). The middle cerebral artery peak systolic velocities and CI had a correlation of .36 (P = .0181). The equation, derived from the linear relation between OBF and CI, was then validated on a sample of 15 patients. With the apparent linear relation between OBF and CI, we used the derived equation to predict CI from OBF. The OBF determination predicted CI within 30% in all patients and within 20% in 53.3% of the patients.

We demonstrated that OBF and middle cerebral artery systolic velocity decrease with diminishing CI. Our findings suggest that CI may be potentially estimated in selected patients by noninvasive assessment of OBF using ocular pneumoplethysmography.
Cerebral hypoperfusion in stroke prognosis and brain recovery.
Authors: Davis S M , Chua M G , Lichtenstein M , Rossiter S C , Binns D , Hopper J L
Published: June 2011

The value of acute cerebral blood flow measurements in stroke prognosis is controversial. No previous study has determined whether acute perfusion deficits independently add to a validated clinical prognostic score. We aimed to compare the value of acute hypoperfusion deficits with a quantitative clinical score in stroke prognosis and to correlate the changes in perfusion with brain recovery.

Volumetric analysis of regional hypoperfusion was performed in 38 patients with middle cerebral infarction within 72 hours of onset by use of single photon emission computed tomography and 99mTc hexamethylpropylene amine oxime. Stroke severity was assessed by the Canadian Neurological Score and Barthel Index. Allen's prognostic score was determined acutely in all patients. Clinical outcome was evaluated in 36 of 38 patients, of whom 18 had repeat blood flow studies.

Acute hypoperfusion correlated with both the outcome Barthel Index (P < .001, r = -.61) and Canadian Neurological Score (P < .001, r = -.64). Allen's score correlated better with both the outcome Barthel Index (P < .001, r = .80) and Canadian Neurological Score (P < .001, r = .81). Acute hypoperfusion deficits, after allowing for Allen's score, independently predicted neurological but not functional outcome. Despite overall neurological improvement, mean hypoperfusion increased on the repeat blood flow studies (P < .05).

Volumetric analysis of acute regional hypoperfusion within 72 hours of onset predicts stroke outcome after 3 months, but Allen's score is a better prognostic method. Neurological recovery is not associated with chronic infarct reperfusion.
Neuroprotection by excitatory amino acid antagonist augments the benefit of thrombolysis in embolic stroke in rats.
Authors: Sereghy T , Overgaard K , Boysen G
Published: June 2011

The effects of delayed thrombolysis with alteplase and neuroprotection with an excitatory amino acid receptor antagonist and their combination were tested in an embolic stroke model.

In 61 rats the carotid artery territory was embolized with arterial-like fibrin-rich clots. Hemispheric cerebral blood flow before and after embolization was measured by intra-arterial 133Xe injection method. The animals were assigned to one of the following treatments: (1) vehicle-treated controls (n = 15); (2) dizocilpine 1 mg/kg i.v. 5 minutes after embolization (n = 16); (3) alteplase 20 mg/kg as an intravenous continuous infusion starting 2 hours after embolization (n = 16); and (4) both agents (n = 14). Carotid angiography displayed the site of occlusion of the cerebral arterial tree immediately after and 3 hours after embolization, and the clinical neurological score was assessed after the rats recovered from anesthesia and before the rats were killed. Brains were fixed after 2 days and evaluated neuropathologically; infarct volume affecting cortical and deep brain structures was measured separately.

Both alteplase and dizocilpine reduced the total infarct volume (P = .05 and P = .04, respectively, Mann-Whitney tests). Dizocilpine reduced the incidence of cortical infarctions by 48% (P < .001, Fisher's test). Only the combined treatment significantly reduced deep brain infarctions (P = .03, Mann-Whitney test). The combined treatment also improved the clinical score by 83% compared with controls, by 75% compared with the group treated by dizocilpine alone, and by 50% compared with the group treated by alteplase alone. Sixty-seven percent of thrombolytic-treated animals recanalized completely compared with 39% of those given no thrombolytics (P = .05, Fisher's test). The clinical outcome correlated with infarct size (P < .01, Spearman test).

Our results document comparable efficacy of delayed thrombolysis and excitatory amino acid receptor antagonism in this model and suggest that combination of these two therapeutic approaches may yield additional benefit in treatment of thromboembolic stroke, particularly in cases where deep brain (end-artery-supplied) structures are affected.
Hemiplegia due to posterior cerebral artery occlusion.
Authors: North K , Kan A , de Silva M , Ouvrier R
Published: June 2011

Hemiplegia is a rare manifestation of posterior cerebral artery occlusion. The acute clinical picture may be difficult to differentiate from occlusion of the middle cerebral artery. A mechanism for the hemiplegia has not been conclusively determined.

We describe a patient with hemiplegia secondary to posterior cerebral artery occlusion by an embolized fragment of a prosthetic valve. Computed tomographic scan showed the foreign body just distal to the origin of the posterior cerebral artery with infarction of its vascular territory. These findings were later confirmed at autopsy. There was no radiological or autopsy evidence of involvement of the other cerebral arteries or their territories.

The patient provides further evidence that occlusion of the posterior cerebral artery just distal to its junction with the posterior communicating artery may produce contralateral hemiplegia without oculomotor nerve nucleus involvement.
Upper limb somatosensory evoked potentials as a predictor of rehabilitation progress in dominant hemisphere stroke patients.
Authors: Keren O , Ring H , Solzi P , Pratt H , Groswasser Z
Published: June 2011

The aim of this study was to determine the predictive yield of upper limb short latency somatosensory evoked potential (USEP) in patients with first stroke in the dominant hemisphere.

Nineteen patients (average age, 58 years) were evaluated twice: on arrival at the rehabilitation center, approximately 3 weeks after the stroke, and again approximately 10 weeks later. The clinical assessment included a quantitative evaluation of motor ability, independence in activities of daily living, and communication ability. USEP was recorded during the week of the initial clinical evaluation. Special attention was paid to the relations between USEP parameters and the dynamics of the clinical condition.

The seven patients in whom no cortical potential could be detected showed the worst outcomes; however, the existence of cortical potentials in the remaining 12 patients did not provide a precise prediction of their "rehabilitative capacity" (ie, the extent of their progress). A correlation was established between the amplitude of the potentials recorded over both hemispheres and changes in communication ability. Additional findings included an association between shortened central conduction time over the damaged hemisphere during the first month after stroke and improvement in motor ability.

USEP can serve as an adjuvant tool for predicting the recovery progress of stroke patients.
Regular light-to-moderate intake of alcohol and the risk of ischemic stroke. Is there a beneficial effect?
Authors: Palomäki H , Kaste M
Published: June 2011

To evaluate the association between different patterns of alcohol consumption and the risk of ischemic stroke in young or middle-aged men.

One hundred fifty-six patients and 153 control subjects were included in this case-control study. The pattern and the estimated average weekly intake of alcohol were assessed using a structured questionnaire. The pattern of drinking was defined as regular (daily or almost daily) or irregular (up to three times per week), and the weekly amount of consumption was defined as nondrinking, light-to-moderate drinking (up to 150 g/wk), moderate drinking (> 150 to 300 g/wk), and heavy drinking (> 300 g/wk). Multiple stepwise logistic regression models were used, and adjustments were carried out for potential confounders.

Heavy alcohol intake associated with an increased risk of stroke (odds ratio, 4.45; 95% confidence interval, 1.09 to 18.1), whereas the risk tended to be reduced in light-to-moderate drinkers (odds ratio, 0.54; 95% confidence interval, 0.28 to 1.05). Accounting for the pattern of alcohol intake in addition to the average weekly amount in grams, regular light-to-moderate drinking showed a significant inverse association with stroke (odds ratio, 0.12; 95% confidence interval, 0.02 to 0.65), and an irregular pattern of consumption attenuated this association. Based on the same multivariate analyses, other significant independent risk factors for stroke were arterial hypertension, coronary heart disease, and history of snoring, whereas the contributions of age, diabetes mellitus, smoking, and body mass index proved to be nonsignificant.

Light-to-moderate alcohol intake appears to have an inverse association with the risk of ischemic stroke. The beneficial effect appears to be most prominent if the consumption of alcohol is regular and evenly distributed throughout the week, whereas a sporadic or an occasional pattern of drinking seems to weaken the association. This study also supports the role of heavy drinking as an independent risk factor for ischemic stroke.
The J-curve phenomenon in stroke recurrence.
Authors: Irie K , Yamaguchi T , Minematsu K , Omae T
Published: June 2011

The relation of poststroke blood pressure to stroke recurrence remains undetermined, and the optimal control of blood pressure has not been established. We performed the present study to resolve these issues.

We analyzed 368 stroke patients with a history of hypertension (mean age, 62 years) who were admitted within 3 months after stroke onset and observed for 6 months or more. We determined stroke recurrence rate in relation to baseline (or initial) blood pressure, mean values of poststroke blood pressure, stroke subtypes, age, antihypertensive treatment, and other clinical features.

The recurrence rate had a J-curve relation to poststroke diastolic blood pressure but not to poststroke systolic blood pressure and baseline diastolic and systolic blood pressures. The stroke recurrence rate was 3.8% per patient-year in 94 patients who had a poststroke diastolic blood pressure of 80 to 84 mm Hg, significantly lower than the rates of 9.2% per patient-year (P < .05) and 11.4% per patient-year (P < .01) in those with a lower and higher poststroke diastolic blood pressure, respectively. The range of poststroke diastolic blood pressure accompanying the lowest stroke recurrence rate was higher in patients with atherothrombotic (85 to 89 mm Hg) than in those with lacunar infarction (80 to 84 mm Hg). Neither antihypertensive therapy nor patients' age affected this phenomenon.

The present study suggests that lower blood pressure does not always result in favorable effects on stroke recurrence. The effects of poststroke blood pressure and antihypertensive therapy on stroke recurrence may be complicated by the J-curve phenomenon.
Clinical analysis of incidentally discovered unruptured aneurysms.
Authors: Ujiie H , Sato K , Onda H , Oikawa A , Kagawa M , Takakura K , Kobayashi N
Published: June 2011

We analyzed the risk factors for rupture of an intracranial aneurysm based on a retrospective angiographic study of ruptured and unruptured aneurysms.

The 44 cases of asymptomatic aneurysms were selected from 1612 patients whose lesions had been discovered fortuitously by angiography (2.7%) during the period from 1980 to 1989. All these patients were free from any sign of intracranial aneurysm. The variations in age, sex, and location of the aneurysms were analyzed compared with 638 ruptured aneurysms that had been treated in our institute during the same period. The size, shape, and arterial geometry of the unruptured aneurysms were examined angiographically.

Unruptured aneurysm was discovered fortuitously in 44 (2.7%) of 1612 patients, with greater incidence in women aged older than 60 years. Unruptured aneurysms were less likely to occur in the anterior communicating artery (12.8%) and the middle cerebral artery (6.4%). However, they were frequently found in the internal carotid artery, with an incidence of 10.6% in cavernous portion of the internal carotid artery, 19.1% in the internal carotid-ophthalmic artery, 19.1% in the internal carotid-posterior communicating artery, and 12.8% in the internal carotid-anterior choroidal artery. Seven of the nine internal carotid-posterior communicating artery aneurysms showed a hypoplastic or aplastic posterior communicating artery. The mean diameter of the unruptured aneurysms was 4.8 mm, and 80% were smaller than 6 mm.

Intracranial aneurysms are formed not only at the bifurcation of an artery but also at its branching and bending points. However, an aneurysm located at the bifurcation, such as the anterior communicating artery and the middle cerebral artery, bleeds easily in contrast with lateral aneurysms such as those found at the branching and bending points on the internal carotid artery.
Computer-assisted three-dimensional image analysis of cerebral amyloid angiopathy.
Authors: Maeda A , Yamada M , Itoh Y , Otomo E , Hayakawa M , Miyatake T
Published: June 2011

Microaneurysms and fibrinoid necrosis of cerebral cortical arteries have been reported to be related to the pathogenesis of intracerebral hemorrhage associated with cerebral amyloid angiopathy. To elucidate the pathogenesis of such vascular lesions, we conducted the present study.

Five hundred serial sections from brain tissue of a patient with severe amyloid angiopathy and intracerebral hemorrhage were analyzed histologically and immunohistochemically. Three-dimensional reconstructions of the vascular lesions were performed using a computer-assisted image analysis system.

The microaneurysms were found to develop in small cortical arteries with diameters of about 40 to 50 microns. They were spindle-shaped dilatations, with a maximum diameter of about 200 microns, and appeared within vascular segments bearing severe amyloid deposition. In the walls of the aneurysms, the intima was thickened, and the media and adventitia showed thinning and disruption. Fibrinoid necrosis was found in the vascular walls of the most dilated, middle portions of the aneurysm. The vascular walls undergoing fibrinoid necrosis did not show any beta/A4 or cystatin C but presented with fibrinogen-like immunoreactivities, indicating invasion of plasma components.

These results suggested the following sequential events for the pathogenesis of the cerebral amyloid angiopathy-associated vascular lesions leading to hemorrhage: (1) damage of the media and adventitia due to severe amyloid deposition results in dilatation of the cortical arteries, (2) the vascular dilatation progresses and is accompanied by thickening of the intima and disruption of the media and adventitia (microaneurysm formation), (3) plasma components invade to the vascular wall (fibrinoid necrosis), and (4) finally, hemorrhage develops.
Cerebral venous thrombosis associated with pregnancy and puerperium. Review of 67 cases.
Authors: Cantú C , Barinagarrementeria F
Published: June 2011

Cerebral venous thrombosis is characterized by its clinical pleomorphism and pathogenetic variability. We studied 67 patients with cerebral venous thrombosis associated with pregnancy and puerperium and compared them with 46 other cases unrelated to obstetric causes to disclose differences in their clinical presentation, neuroradiological findings, clinical course, and prognosis.

In this retrospective study, we analyzed the clinical, laboratory, and neuroimaging findings of 113 patients collected consecutively at our institute. The diagnosis of cerebral venous thrombosis was confirmed by angiography, magnetic resonance imaging, or neuropathological study.

Patients with cerebral venous thrombosis associated with pregnancy and puerperium were younger (average age, 26 versus 36 years), and in most, the onset of symptoms was acute (82% versus 54%; P = .003). The evolution of symptoms reached a plateau within 10 days in 70% of patients with thrombosis from obstetric causes, compared with only 45% in those from other causes (P = .01). Anemia was more frequent in the obstetric group (64% versus 26%; P = .00001). There were no differences regarding neurological and neuroradiological findings. Although the initial severity of illness was similar in both groups, the final outcome was considered good in 80% of patients with obstetric causes, compared with 58% of patients with other causes (P = .01); mortality rates were 9% and 33%, respectively (P = .002).

Cerebral venous thrombosis associated with pregnancy and puerperium has a more acute onset and a better prognosis than thrombosis due to other causes. These findings might be helpful in the diagnostic and therapeutic strategies for patients with cerebral venous thrombosis.
Correlations between morphological changes in platelet aggregates and underlying endothelial damage in cerebral microcirculation of mice.
Authors: Said S , Rosenblum W I , Povlishock J T , Nelson G H
Published: June 2011

The aim of this study was to test the hypothesis that, once formed, platelet aggregates may injure underlying cerebrovascular endothelium. Such injury could make the same site selectively attractive to the next wave of passing emboli or activated platelets. This vicious circle could account for repetitive, stereotypic symptoms in transient ischemic attacks.

In pial arterioles, minor endothelial injury was produced by a laser/dye technique. After various periods of platelet aggregation at the damaged site, the vessels were fixed in situ for electron microscopic study. The degree of platelet activation (rounded and/or degranulated forms) was evaluated by counting these forms in the electron photomicrographs. These counts were related to the degree of endothelial damage ascertained in the micrographs. Other statistical relations were also examined.

Endothelial damage progressed in parallel with the duration of platelet aggregation and the degree of platelet degranulation at the site. Correlations were number of activated platelets versus degree of damage, r = .43, P < .03; duration of aggregation versus damage, r = .52, P < .01; and number of degranulated platelets versus the degree of endothelial damage, r = .83, P < .001. If an aggregate embolized, endothelial damage did not appear to progress. No correlation existed between the duration of exposure to the laser and the degree of injury.

The parallel between changes in platelets and endothelial damage could represent either an effect of endothelium on platelets or an effect of platelets on endothelium. Although the former alternative cannot be totally ruled out, the observations seem to fit best the hypothesis that progressive endothelial damage can result from increasing activation and degranulation of overlying platelets.
Effect of phorbol myristate acetate on cerebral blood flow in normal and neutrophil-depleted rats.
Authors: Uhl M W , Kochanek P M , Schiding J K , Nemoto E M
Published: June 2011

Recent evidence suggests a possible role for leukocytes in ischemic brain injury. This study examined the effect of activation of endogenous circulating leukocytes on cerebral blood flow in normal and neutrophil-depleted rats.

Leukocytes were activated by rapid injection of either 50 micrograms/kg phorbol 12-myristate 13-acetate, a protein kinase C activator, or an equimolar amount of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine, into the right carotid artery. Control rats received an equal volume of dimethyl sulfoxide in saline vehicle. H2-clearance cerebral blood flow was measured in each of the three groups and in vinblastine-treated, neutrophil-depleted rats after carotid artery injection of phorbol.

Phorbol 12-myristate 13-acetate dramatically decreased circulating leukocyte and platelet counts from 5 to 120 minutes after infusion and decreased regional cerebral blood flow in the ipsilateral parietal cortex from a baseline of 119 +/- 14 mL.min-1.100 g-1 (mean +/- SEM) to 49 +/- 5 mL.min-1.100 g-1 at 30 minutes (P < .05). Decreased flow persisted for the 2-hour study. Neither N-formyl-methionyl-leucyl-phenylalanine or vehicle had an effect on cerebral blood flow. In the neutrophil-depleted rats the initial decrease in cerebral blood flow at 30 and 60 minutes after infusion of phorbol was observed, but cerebral blood flow was restored to 70% to 80% of its baseline value (P > .05 versus baseline) by 90 to 120 minutes.

The early phorbol 12-myristate 13-acetate-induced decrease in cerebral blood flow may be due to the effects of protein kinase C activation on vascular smooth muscle or on platelet aggregation, whereas the persistent decrease in cerebral blood flow appears to be mediated in part by neutrophil activation.
Acidic foci within the ischemic penumbra of the New Zealand white rabbit.
Authors: Tomlinson F H , Anderson R E , Meyer F B
Published: June 2011

In vivo panoramic imaging of reduced nicotinamide adenine dinucleotide (NADH), intracellular brain pH (pHi), and cortical blood flow was used to characterize the ischemic penumbra during focal ischemia. During global ischemia, hypoxia, and status epilepticus, the development of cortical acidic foci has been observed. The hypothesis tested was that during focal ischemia, acidic foci develop, which may lead to recruitment of the ischemic penumbra into infarction.

Five fasted New Zealand White rabbits underwent middle cerebral artery (MCA) occlusion under 1.5% halothane anesthesia through a retro-orbital approach, and five animals served as controls. Brain pHi and cerebral blood flow were measured with in vivo umbelliferone fluorescence.

Baseline brain pHi was 6.98 +/- 0.05, whereas cortical blood flow and NADH fluorescence measured 52.2 +/- 8.7 mL/100 g per minute and 35.5 +/- 3.7 gray-scale units, respectively. Fifteen minutes after MCA occlusion, overall brain pHi and cortical blood flow of the ischemic penumbra measured 6.61 +/- 0.06 and 31.9 +/- 9.2 mL/100 g per minute. Over 3 hours there was normalization of pHi in the majority of the penumbra due to increases in cortical blood flow. Within the ischemic penumbra acidic foci developed with an initial pHi of 6.35 +/- 0.09 and cortical blood flow of 18.0 +/- 5.7 mL/100 g per minute. These foci remained acidic with increased NADH fluorescence despite being surrounded by cortex that was recovering from ischemia. On light microscopy, these acidic foci had a mixed pattern of neuronal injury.

Within the ischemic penumbra, acidic foci develop that do not follow a vascular distribution and have microscopic evidence of ischemic neuronal injury. This suggests that there is a cortical selective vulnerability regarding pHi regulation and these acidic foci may lead to recruitment of the ischemic penumbra into infarction.
Comparative effects of angiotensin-(1-7) and angiotensin II on piglet pial arterioles.
Authors: Meng W , Busija D W
Published: June 2011

Recent investigations indicated that degradation fragments of angiotensins could be involved in the regulation of the cerebral circulation and that their effects might be mediated by prostaglandins. The present study was designed to examine the effect of angiotensin-(1-7), a major endogenous heptapeptide fragment, on cerebral arteriolar diameter and compare it with the octapeptide angiotensin II, and further to determine whether prostaglandins mediate their effects.

Newborn, anesthetized pigs were equipped with a closed cranial window, and the diameter of one pial arteriole was measured using intravital microscopy.

Topical application of angiotensin-(1-7) (n = 9) increased the diameter by 6.8 +/- 5.3% (mean +/- SEM), 10.4 +/- 5.2%, 14.3 +/- 5.9%, and 17.5 +/- 7.7% (P < .05) at 10(-7), 10(-6), 10(-5), and 10(-4) mol/L, respectively (baseline, 94 +/- 3 microns). Topical application of angiotensin II (n = 8) increased the diameter by 9.6 +/- 7.0%, 9.6 +/- 7.6%, 11.3 +/- 8.4% (P < .05), and 5.5 +/- 7.9% at 10(-7), 10(-6), 10(-5), and 10(-4) mol/L, respectively (baseline, 94 +/- 5 microns). After administration of indomethacin (5 mg/kg IV), which did not significantly change the baseline arteriolar diameter, neither angiotensin-(1-7) at 10(-4) mol/L nor angiotensin II at 10(-5) mol/L caused significant vasodilation.

The results indicate that angiotensin-(1-7) is a modest dilator in the cerebral circulation, as is angiotensin II, and that prostaglandins may mediate responses.
Effect of cerebral blood flow generated during cardiopulmonary resuscitation in dogs on maintenance versus recovery of ATP and pH.
Authors: Eleff S M , Kim H , Shaffner D H , Traystman R J , Koehler R C
Published: June 2011

Cardiopulmonary resuscitation with external chest compression generates low perfusion pressures that may be inadequate for restoring cerebral metabolism and may worsen intracellular pH. We tested the hypothesis that cerebral reperfusion with a low perfusion pressure after arrest restores brain adenosine triphosphate (ATP) and pH to levels attained at the same perfusion pressure without preceding complete ischemia.

Brain ATP and intracellular pH were measured by magnetic resonance spectroscopy, and cerebral blood flow was measured with microspheres in anesthetized dogs. External chest compressions were begun in group A (n = 6) immediately after the onset of arrest (ie, arrest time zero) and in group B (n = 10) after 6 minutes of arrest (ie, arrest time 6 minutes). In both groups, mean cerebral perfusion pressure was regulated at 30 mm Hg for 70 minutes by adjustment of inflation pressure of a pneumatic thoracic vest.

At 12 minutes of resuscitation, cerebral blood flow was 27 +/- 4 mL/min per 100 g in group A and 21 +/- 4 mL/min per 100 g in group B, but ATP in group B (58 +/- 10% of prearrest) was less than in group A (105 +/- 6%). With prolonged resuscitation, ATP deteriorated to near zero levels in dogs in group B, with blood flow less than 15 mL/min per 100 g. Dogs with greater blood flow never achieved complete metabolic recovery. In group B, intracellular pH was unchanged from the 6.3 value at the start of resuscitation, even in those dogs with extremely low blood flows.

Levels of cerebral perfusion pressure sufficient to maintain cerebral oxidative metabolism without complete ischemia during cardiopulmonary resuscitation are not sufficient to restore metabolism after complete ischemia during cardiopulmonary resuscitation. However, low "trickle" blood flow did not worsen intracellular acidosis.
Anatomic variation of the middle cerebral artery in the Sprague-Dawley rat.
Authors: Fox G , Gallacher D , Shevde S , Loftus J , Swayne G
Published: June 2011

The aim of this study was to record and analyze the anatomy of the middle cerebral artery in the rat in an attempt to identify a potential source of variation of quantitative infarct measurements in commonly used models of focal cerebral ischemia.

Over a period of 22 months, as part of ongoing studies, we routinely induced focal cerebral ischemia in 263 Sprague-Dawley rats. This was achieved by permanent occlusion of a length of the right middle cerebral artery approximately 1 to 5 mm distal to the point at which it traverses the rhinal fissure combined with 60 minutes of bilateral common carotid occlusion. The branching pattern of the middle cerebral artery was recorded for each animal by drawing and photography before occlusion and at the time of death.

Six distinct branching patterns were observed. The majority (82.9%) of middle cerebral arteries studied conformed to the typical bifurcating vessel commonly referred to in the literature. However, the remaining 17.1% were far more variable with major, atypical branching, introducing, we believe, unnecessary and avoidable variation into quantitative measurements of ischemia in this and similar models.

Middle cerebral artery anatomy should be routinely recorded in models of focal cerebral ischemia in which this artery is occluded distal to the olfactory tract, thus allowing improved analysis of data.
Accelerated brain infarction in hypertension complicated by hereditary heterozygous protein C deficiency.
Authors: Kazui S , Kuriyama Y , Sakata T , Hiroki M , Miyashita K , Sawada T
Published: June 2011

Protein C deficiency leads to reduced inhibition of coagulation and an increased likelihood of thrombosis. It is widely accepted that the most common syndromes associated with protein C deficiency are venous thrombosis and pulmonary thromboembolism, whereas arterial thrombosis is rare. Here we describe two patients with hypertension and hereditary heterozygous protein C deficiency who developed multiple lacunar infarcts.

Patient 1 was a 46-year-old man with a history of hypertension who developed a right upper quadrantanopia and gradually progressive intellectual and behavioral deterioration. Patient 2 was a 61-year-old man with history of hypertension and two episodes of right-sided motor weakness who developed left sixth and seventh cranial-nerve palsies and reduced pinprick sensation in the right extremities. In both patients, magnetic resonance imaging revealed multiple small lesions in the pons as well as the bilateral basal ganglia, thalamus, corona radiata, and other subcortical structures, which are consistent with lacunar infarcts. Protein C activity and antigen levels were reduced to approximately one half of normal in these two patients, as well as in some of their family members who had no other serological or coagulation abnormalities. A diagnosis of heterozygous protein C deficiency type 1 was thus established.

Although it remains uncertain whether protein C deficiency itself increases the risk of cerebral artery thrombosis, it may predispose a patient to develop multiple brain infarctions in association with hypertension.
Congenitally abnormal plasminogen in juvenile ischemic cerebrovascular disease.
Authors: Nagayama T , Shinohara Y , Nagayama M , Tsuda M , Yamamura M
Published: June 2011

Congenitally abnormal plasminogen is characterized by markedly decreased fibrinolytic activity and has been reported mainly in association with venous occlusive disease.

We found three young adult patients (34, 45, and 27 years old at onset) with ischemic cerebrovascular disease, all of whom had congenital plasminogen abnormalities but no other known risk factors. Hemostatic tests of all three patients revealed plasma plasminogen activities at almost one half of the normal level despite normal plasma plasminogen antigen levels. They were found to be heterozygotes with abnormal plasminogen (normal Ala-601[GCT] to abnormal Thr-601[ACT]) by DNA sequence analysis after polymerase chain reaction.

Congenital plasminogen abnormalities could be one of the risk factors of juvenile ischemic cerebrovascular disease of the arterial as well as venous type.
Postpartum cerebral angiopathy. Is there a role for sympathomimetic drugs?
Authors: Raroque H G , Tesfa G , Purdy P
Published: June 2011

Postpartum cerebral angiopathy is associated with the use of of ergot alkaloids. The exact mechanism is unclear but may be related to their sympathomimetic properties, as evidenced in patients already on other ergot derivatives who deteriorated only after taking additional sympathomimetic drugs. We postulate that sympathomimetic agents, independent of ergot alkaloids, may produce the same complication.

A postpartum patient, initially presenting with headaches, subsequently manifested rapid neurological deterioration after ingesting isometheptene, a sympathomimetic drug. She was not on any ergot derivative but presented similar clinical and radiological manifestations. She experienced increased headache severity, visual disturbance, and seizures associated with multiple segmental cerebral vasoconstriction on angiography and increased T2-weighted signal in the occipital areas on magnetic resonance imaging.

This case is additional evidence that sympathomimetic actions of some drugs, such as ergot derivatives and isometheptene, may lead to postpartum cerebral angiopathy. Documentation of medication used by postpartum women suffering similar complications is needed to verify these findings.
The use of expected value as an aid to decisions regarding anticoagulation in patients with atrial fibrillation.
Authors: Nadeau S E
Published: June 2011

The method described provides a rational means for determining whether to institute chronic anticoagulation to prevent stroke in patients with chronic atrial fibrillation under a variety of clinical circumstances.

The concept of expected value is used in conjunction with data from clinical studies to define the net value of anticoagulation to the patient. A full year of anticoagulation is warranted in patients with recent stroke or transient ischemic attack thought to be due to cardiogenic embolism who feel that stroke is a very serious event with nearly as much disvalue as death. If stroke has a lesser degree of negative value to the patient, or it is uncertain whether the stroke was in a large-vessel distribution, or it is uncertain whether a large-vessel distribution stroke was due to cardiogenic embolism, 6 months or less of anticoagulation may be warranted. Indefinite anticoagulation is justifiable in most patients with chronic atrial fibrillation without a history of stroke or transient ischemic attack but may be contraindicated in certain patients at extremely low risk for embolism and in patients who place a low value on stroke relative to death and who have a modest increase in risk for fatal hemorrhage.

The method described provides a means readily usable by clinicians to make anticoagulation decisions in patients with chronic atrial fibrillation that will address risk-benefit tradeoffs with somewhat greater precision than current approaches.
Distribution of atherosclerosis and risk factors in atherothrombotic occlusion.
Authors: Yasaka M , Yamaguchi T , Shichiri M
Published: June 2011

The present study was performed to determine the relation between distribution of atherosclerosis and risk factors in Japanese patients with atherothrombotic occlusion.

We studied 154 patients with atherothrombotic occlusion of the extracranial internal carotid artery (n = 75, ICA group), the horizontal portion of the middle cerebral artery (n = 47, MCA group), and the basilar artery (n = 32, BA group), all of which were confirmed by cerebral angiography. We investigated the distribution of atherosclerosis of the three sites and compared the risk factors for atherosclerosis between the three groups. We used 113 subjects without stroke as the control group.

A strong correlation was present between atherosclerosis of the extracranial internal carotid artery and that of the basilar artery. However, only a weak correlation existed between atherosclerosis of the middle cerebral artery and that of the other vessels. Although the prevalence of smoking and hypertension was higher and high density lipoprotein cholesterol levels were lower in the three groups than in the control subjects, no significant differences were found in age, sex, prevalence of smoking and hypertension, serum levels of triglycerides, and high density lipoprotein cholesterol among the three groups. The prevalence of coronary heart disease and diabetes mellitus and the serum levels of hemoglobin A1c, total cholesterol, and low density lipoprotein cholesterol were higher in the ICA and BA groups than in the MCA group. The prevalence of electrocardiographic evidence of left ventricular hypertrophy was higher in the MCA group than in the other groups.

In addition to smoking, hypertension, and low concentration of high density lipoprotein cholesterol, diabetes mellitus and hypercholesterolemia seem to be associated with atherosclerosis of the extracranial internal carotid artery and the basilar artery, and advanced hypertension may play a role in the development of middle cerebral artery occlusion.
Neuropathologic changes in the gerbil brain after chronic hypoperfusion.
Authors: Kudo T , Takeda M , Tanimukai S , Nishimura T
Published: June 2011

An animal model has been developed to elucidate the pathological changes in brain cytoskeletal proteins during chronic hypoperfusion.

Newly designed coiled clips were placed around both carotid arteries of Mongolian gerbils (n = 10) to cause stenosis without occlusion. Those gerbils showing impaired learning ability by the passive avoidance paradigm were killed for neuropathologic study after 12 weeks.

The brains showed ventricular dilatation, cortical atrophy, and rarefaction of the white matter. Immunoreactivity to anti-microtubule-associated protein 2 antibody in the cerebral cortex and the hippocampus was diminished, indicating dendritic changes of neurons. In the thalamic axonal regions, staining with anti-neurofilament 200K protein antibody was increased, suggesting increased amounts of neurofilament proteins or increased phosphorylation of the protein. Increased immunoreactivity to anti-glial fibrillary acidic protein antibody was observed in a wedge-shaped configuration, corresponding to the border zone of perfusion by small vessels.

These findings suggest that changes in the cytoskeletal proteins in dendrites, axons, and glial cells may cause neuronal death under conditions of chronic cerebral hypoperfusion.
Cerebral blood flow in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes.
Authors: Ooiwa Y , Uematsu Y , Terada T , Nakai K , Itakura T , Komai N , Moriwaki H
Published: June 2011

The precise mechanism of neurological symptoms with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) is still controversial. We investigated the correlation between strokelike episodes and cerebral blood flow in two patients with MELAS and discuss the pathogenesis of strokelike episodes with MELAS.

Cerebral dynamic computed tomography and cerebral angiography were used to measure cerebral circulation in the first case, that of a 20-year-old woman with MELAS. The second subject was a 13-year-old female who was studied with xenon-enhanced computed tomography. The cerebral blood flow studies were performed 3-72 hours after the onset of strokelike episodes. Serial cerebral angiography, dynamic computed tomography, and xenon-enhanced computed tomography showed vasodilation localized in the affected cerebral cortexes during strokelike episodes, without any reduction in regional cerebral blood flow.

Our study suggests that the strokelike episodes associated with MELAS are different in origin from ischemic stroke.
Aspirin response and failure in cerebral infarction.
Authors: Helgason C M , Tortorice K L , Winkler S R , Penney D W , Schuler J J , McClelland T J , Brace L D
Published: June 2011

The purpose of this study was to assess the biological effect of aspirin as measured by the inhibition of platelet aggregation in patients taking aspirin for stroke prevention and in patients with acute stroke.

We administered increasing doses of aspirin (325, 650, 975, and 1,300 mg daily) to 113 patients for stroke prevention and measured the inhibition of platelet aggregation in these patients and in 33 patients with acute stroke taking aspirin before stroke onset.

Eighty-five patients on < or = 325 and six on > or = 650 mg aspirin had complete inhibition of platelet aggregation. Increase of the dose by 325 mg in nine of the 22 patients with partial inhibition of platelet aggregation produced complete inhibition in five patients at 650 mg and in one at 975 mg. At 1,300 mg, three patients still had only partial inhibition of platelet aggregation (aspirin resistance). Of the 33 inpatients with acute stroke, 24 had platelet aggregation studies done before further administration of aspirin. Of these, 19 had complete inhibition of platelet aggregation and three had partial inhibition, with production of complete inhibition of platelet aggregation at dose escalation; one patient was aspirin-resistant and the other noncompliant.

How the inhibition of platelet aggregation relates to stroke prevention remains unclear. The ability of aspirin and the dose required to inhibit platelet aggregation may depend upon the individual.
Vascular dimensions of the cerebral arteries follow the principle of minimum work.
Authors: Rossitti S , Löfgren J
Published: June 2011

The principle of minimum work is a parametric optimization model for the growth and adaptation of arterial trees. It establishes a balance between energy dissipation due to frictional resistance of laminar flow (shear stress) and the minimum volume of the vascular system, implying that the radius of the vessel is adjusted to the cube root of the volumetric flow. The purpose of this study is to verify whether the internal carotid artery system obeys the principle of minimum work.

Measurements of the radius of parent and branch segments of the internal carotid, anterior, and middle cerebral arteries were performed on analog angiographs chosen at random from a set classified as normal. The branch angles were measured from lateral projections in bifurcations of the anterior cerebral artery. The relation of the calibers of parent and branch vessels was analyzed.

The area ratio of the bifurcations (N = 174) was 1.2 +/- 0.4 (mean +/- SD). The equation (r0)n = (r1)n + (r2)n was solved for n, resulting in n = 2.9 +/- 0.7 (mean +/- SD, N = 157). Optimum proportions between the radii of parent (r0) and branch (r1 and r2) vessels in the internal carotid artery system were verified in normal carotid angiographs up to four branch generations, according to the theoretical equation r0(3) = r1(3) + r2(3) (r = 0.989, N = 174). No clear correlation was found between the measured branch angles, the relative branch cross-sectional area, and the theoretical optimum angles.

This study demonstrates that the process of branching of the internal carotid artery system obeys the principle of minimum work, as the diameter exponent approximates 3. The principle of minimum work establishes strict functional relations between volumetric flow, flow velocity, and vessel radius. This model was extended to parametric optimization of branch angles, which has proved irrelevant in terms of functional optimization. Our results corroborate this finding. Shear stress-induced endothelial mediation seems to be the regulating mechanism for the maintenance of this optimum vessel design. The magnitude of wall shear stress is the same at every point in a vascular network obeying the principle of minimum work, because the flow rate influences the shear stress proportionally to the third power of the vessel radius. This observation has implications for understanding the remodeling of the cerebral vascular network in the presence of arteriovenous malformations and for the pathogenesis of saccular aneurysms.