bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion.
Authors: Nagasawa H , Kogure K
Published: June 2011

We describe a new focal ischemia model consisting of unilateral middle cerebral artery occlusion with a silicone rubber cylinder attached to a nylon surgical thread inserted through the internal carotid artery in rats. Recirculation was accomplished by pulling the thread out of the artery. We evaluated the reliability of this model and studied the influence of reperfusion of the brain by measuring regional cerebral blood flow in 30 rats and by using conventional neuropathologic methods after different periods of occlusion in 48 rats. The anterior neocortex and the lateral part of the caudate putamen, which were supplied by the occluded middle cerebral artery, were the regions most frequently damaged. After 1 hour of occlusion in five rats, in the cortex supplied by the occluded artery mean +/- SD blood flow was 0.19 +/- 0.08 ml/g/min (approximately 15% of that in the corresponding region of five sham-operated control rats), and mild scattered ischemic cell change was observed. Three (n = 5) or six (n = 5) hours of occlusion reduced blood flow more severely and caused severe ischemic cell changes in the cortex supplied by the occluded artery in proportion to the duration of ischemia. Characteristically, in five rats subjected to 3 hours of occlusion followed by 3 hours of recirculation, blood flow was restored and spongy edematous change was observed in the cortex supplied by the recirculated artery. This change resulted in hypoperfusion of the neighboring cortical region surrounding the recirculated area. Our model should be useful in various investigations of the influence of reperfusion on focal ischemic brain injury.
Occlusion of the middle cerebral artery due to cysticercotic angiitis.
Authors: Rodriguez-Carbajal J , Del Brutto O H , Penagos P , Huebe J , Escobar A
Published: June 2011

Three patients with cysticercosis developed a cerebral infarct secondary to the occlusion of the middle cerebral artery or its major branches. Histopathologic examination revealed a large subarachnoid cysticercus surrounding the occluded arteries in two patients and diffuse thickening of the leptomeninges in one. Blood vessels around the parasite showed inflammatory changes that caused either occlusive endarteritis or thrombosis due to disruption of the endothelium. Cysticercosis should be considered as a cause of occlusion of the major intracranial vessels, particularly in young patients living in areas where this disease is endemic.
Spontaneous intracranial carotid artery dissection.
Authors: Pessin M S , Adelman L S , Barbas N R
Published: June 2011

A previously healthy 46-year-old woman had the abrupt onset of aphasia and right hemiplegia from a large left-hemisphere infarct. At postmortem examination the cause of the infarct was dissection and occlusion of the intracranial carotid artery. No preexisting abnormality was found to account for the dissection. This uncommon cause of stroke and its pathogenesis are discussed.
Determinants of early recurrence of cerebral infarction. The Stroke Data Bank.
Authors: Sacco R L , Foulkes M A , Mohr J P , Wolf P A , Hier D B , Price T R
Published: June 2011

We studied 1,273 patients with ischemic cerebral infarction who were entered into the Stroke Data Bank, a prospective, observational study involving four university hospitals and the Biometry and Field Studies Branch of the National Institute of Neurological Disorders and Stroke. Forty patients had noniatrogenic recurrent stroke within 30 days after the index cerebral infarction. Using life tables, the 30-day cumulative +/- SE risk of early recurrence for all infarctions was 3.3 +/- 0.4%. The risk of early recurrence was greatest for atherothrombotic infarction (7.9 +/- 2.2%, eight of 113 patients) and least for lacunar infarction (2.2 +/- 1.2%, eight of 337 patients). Both cardioembolic infarction (4.3 +/- 0.9%, 10 of 246 patients) and infarction of undetermined cause (3.0 +/- 0.5%, 14 of 508 patients) had intermediate risks. History of hypertension and diabetes mellitus, as well as diastolic hypertension and elevated blood sugar concentration at admission, were associated with early recurrence. Logistic regression analysis estimated the risk of early recurrence to be 8.56% in those with coexisting hypertension and a glucose concentration of 300 mg/dl versus 0.77% in the absence of these two abnormalities. Early recurrence was associated with longer median duration of initial hospital stay (27 vs. 14 days) and a higher 30-day case-fatality rate (20% vs. 7.4%). Increased weakness scores were associated with early recurrent stroke. Identification of the determinants of early recurrent stroke may lead to better secondary prevention and may help select high-risk patients for further study.
Regional cerebral blood flow measurement with intravenous [15O]water bolus and [18F]fluoromethane inhalation.
Authors: Herholz K , Pietrzyk U , Wienhard K , Hebold I , Pawlik G , Wagner R , Holthoff V , Klinkhammer P , Heiss W D
Published: June 2011

In 20 patients with ischemic cerebrovascular disease, classic migraine, or angiomas, we compared paired dynamic positron emission tomographic measurements of regional cerebral blood flow using both [15O]water and [18F]fluoromethane as tracers. Cerebral blood flow was also determined according to the autoradiographic technique with a bolus injection of [15O]water. There were reasonable overall correlations between dynamic [15O]water and [18F]fluoromethane values for cerebral blood flow (r = 0.82) and between dynamic and autoradiographic [15O]water values for cerebral blood flow (r = 0.83). We found a close correspondence between abnormal pathologic findings and visually evaluated cerebral blood flow tomograms obtained with the two tracers. On average, dynamic [15O]water cerebral blood flow was 6% lower than that measured with [18F]fluoromethane. There also was a general trend toward a greater underestimation with [15O]water in high-flow areas, particularly in hyperemic areas, probably due to incomplete first-pass extraction of [15O]water. Underestimation was not detected in low-flow areas or in the cerebellum. Absolute cerebral blood flow values were less closely correlated between tracers and techniques than cerebral blood flow patterns. The variability of the relation between absolute flow values was probably caused by confounding effects of the variation in the circulatory delay time. The autoradiographic technique was most sensitive to this type error.
Blood-brain barrier sodium transport limits development of brain edema during partial ischemia in gerbils.
Authors: Betz A L , Ennis S R , Schielke G P
Published: June 2011

Sodium derived from the blood is known to accumulate in brain tissue during the early stages of incomplete ischemia. Our present studies were undertaken to determine the relation between blood-brain barrier sodium transport and the development of ischemic brain edema. Incomplete cerebral ischemia was produced in gerbils by ligation of the left common carotid artery under ether anesthesia. Following recovery from the anesthetic, the gerbis were evaluated for the presence of neurologic symptoms and were divided into symptomatic (n = 77) and asymptomatic (n = 94) groups. Tissue water, sodium, and potassium contents, tissue plasma volume, and brain uptake of 22Na were measured in both groups 1.5, 3, 6, 12, and 24 hours after carotid ligation. There was a progressive accumulation of sodium and water in the ipsilateral cerebral cortex of the symptomatic group compared with either the corresponding contralateral cortex of the same gerbils or with the asymptomatic group. Net changes in brain sodium and potassium concentrations appeared to be the main determinants of fluid accumulation. Brain edema was not due to opening of the blood-brain barrier because the unidirectional transport of 22Na remained low and was even reduced by 35-55% in the ischemic cortex. Nevertheless, this sodium transport activity appeared to be rate-limiting in the development of brain edema during the first 3 hours of ischemia because the rate of sodium accumulation in the tissue was the same as the rate of 22Na transport from the blood to the brain. We conclude that blood-brain barrier sodium transport is an important factor in the formation of ischemic brain edema.
Effect of enhanced capillary activity on the blood-brain barrier during focal cerebral ischemia in cats.
Authors: Shigeno T , Asano T , Mima T , Takakura K
Published: June 2011

We hypothesize that enhanced activity of capillary Na,K-ATPase promotes Na+ influx into the brain and causes early edema formation in focal cerebral ischemia. The pharmacologic suppression of brain capillary Na,K-ATPase as a means to ameliorate edema formation was examined using the middle cerebral artery occlusion model in 36 cats. With the help of a catheter inserted into the middle cerebral artery, the ischemic brain area was directly perfused with 10(-5) M ouabain. Perfusion was maintained as intermittent 15-second pulse injections given every 5 (n = 6) or 2 (n = 6) minutes. By this method, the naturally occurring circulatory conditions during ischemia were not altered. Four hours after ischemia, the cortical specific gravity at each of six locations over the ischemic area was compared with the corresponding ischemic blood flow measured by the H2 clearance technique. The results show that ouabain perfused every 2 minutes significantly ameliorated edema formation compared with six control cats perfused with Krebs-Ringer solution. In a separate series of experiments, the Na+ flux across the blood-brain barrier was studied by injecting 22NaCl together with an intravascular reference (cobalt-57-labeled microspheres 15 microns in diameter) into the ischemic area. The brain uptake index of 22Na was markedly increased in the ischemic cortex of six control cats; ouabain treatment in six cats suppressed the increase of Na+ influx. The results support our hypothesis that brain capillary Na,K-ATPase activity increases during early focal ischemia, leading to enhanced Na+ together with H2O flux across the blood-brain barrier.
Volume therapy in orthostatic transient ischemic attacks.
Authors: Pascual-Leone A , Anderson D C , Larson D A
Published: June 2011

We report the case of an 83-year-old man with recurrent orthostatic transient ischemic attacks despite anticoagulation and crystalloid therapy. An initial cerebral angiogram revealed a nearly occluded right carotid artery with a string sign. Following aggressive volume expansion with albumin, the patient became asymptomatic. A second angiogram demonstrated the resolution of the carotid string sign and unmasked a high-grade, very tight, surgically approachable stenosis. The role of a high intravascular volume status is discussed.
Action of magnesium sulfate in the treatment of preeclampsia-eclampsia.
Authors: Sadeh M
Published: June 2011

Recent evidence supports the concept that cerebral vasospasm is involved in the pathogenesis of eclampsia. Magnesium, which has a beneficial effect in eclampsia, may act by opposing calcium-dependent arterial constriction, thereby relieving vasospasm. Magnesium may also antagonize the increase in intracellular calcium concentration caused by ischemia and thus prevent cell damage and death. Magnesium might have a role in the treatment of cerebral vasospasm and ischemia, such as occurs in subarachnoid hemorrhage, ischemic stroke, and brain trauma.
Somatosensory evoked potentials in rat cerebral cortex before and after middle cerebral artery occlusion.
Authors: Sakatani K , Iizuka H , Young W
Published: June 2011

We recorded somatosensory evoked potentials in pentobarbital-anesthetized rats before and after middle cerebral artery occlusion. Trigeminal (vibrissae), median (forelimb), and sciatic (hind limb) nerve stimuli produced consistent, robust, and sharply localized responses in the trigeminal, forelimb, and hind limb regions of the somatosensory cortex of 18 rats. These regions are situated at sequentially greater distances from the center of infarcts produced by middle cerebral artery occlusion. In eight rats, occlusion 1-2 mm below the rhinal fissure abolished somatosensory evoked potentials in all three cortical region within minutes. Positive wavelets preceding the primary cortical response were also diminished by the occlusion, suggesting that ischemia affected the thalamocortical white matter. Four of these eight rats did not show histologically apparent ischemic involvement of the hind limb cortical region at 3 hours after occlusion; sciatic nerve evoked potentials recovered substantially in all four rats, and the amplitudes exceeded baseline (129 +/- 30% at 1 hour, 173 +/- 33% at 3 hours) in three of the four rats. Three of the eight rats did not have gross ischemic involvement of the forelimb cortical region; median nerve evoked potentials recovered fully in all eight rats, but the amplitudes did not exceed baseline. All eight rats had evidence of ischemic damage in the trigeminal cortex; no rat showed full recovery in this region, and all but one had trigeminal evoked potentials that were less than 20% of baseline amplitudes by 3 hours after occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Cyclosporine A reduces cerebral vasospasm after subarachnoid hemorrhage in dogs.
Authors: Peterson J W , Nishizawa S , Hackett J D , Bun T , Teramura A , Zervas N T
Published: June 2011

The double subarachnoid hemorrhage canine model was used to test the prophylactic value of immunosuppression in the prevention of cerebral vasospasm after subarachnoid hemorrhage. Dogs treated with cyclosporine A following the regimen prescribed for organ transplant procedures in patients showed a significant reduction in the severity of angiographic constriction of cerebral arteries. While basilar artery diameter after double experimental subarachnoid hemorrhage in a series of untreated dogs (n = 34) averaged 65% of baseline diameter, arterial diameter in dogs treated prophylactically (n = 18) with 6 mg/kg/day cyclosporine A and adjunct low-dose steroid averaged 80% of baseline diameter, for a mean reduction in the severity of chronic arterial constriction of 42%. More important than the average effect, however, is the statistical observation that this mean improvement was obtained primarily by a dramatic reduction in the incidence of severe cerebral vasospasm, the situation most likely to account for morbidity and mortality after aneurysmal rupture.
Multiple cranial neuropathy as a feature of internal carotid artery dissection.
Authors: Panisset M , Eidelman B H
Published: June 2011

The traditional presentation of spontaneous internal carotid artery dissection includes ipsilateral hemicranial headache, oculosympathetic paresis, and contralateral focal cerebral ischemic deficits. However, we describe two cases with multiple cranial nerve involvement ipsilateral to the dissection as the principal feature. The first patient, a 36-year-old man, had involvement of the 9th, 10th, 11th, and 12th cranial nerves. The second case was a 53-year-old man with abnormalities of the 5th, 7th, 9th, 10th, and 12th cranial nerves. In both, magnetic resonance imaging revealed a ring-like area of abnormal signal intensity surrounding the carotid artery at the skull base. Carotid angiography was consistent with the suggestion of dissection on the magnetic resonance studies in both cases. The patients recovered without anticoagulation. Internal carotid artery dissection may thus present with multiple cranial nerve palsies, which could be mistaken for an infiltrating tumor of the skull base. Magnetic resonance imaging is useful in identifying the condition.
Thromboembolic complications in atrial fibrillation.
Authors: Petersen P
Published: June 2011

I review the present understanding of thromboembolic complications and their prevention in patients with nonrheumatic atrial fibrillation. Chronic atrial fibrillation carries an annual 3-6% risk of thromboembolic complications, which is 5-7 times greater than that of controls with sinus rhythm. Paroxysmal atrial fibrillation is associated with a lower risk of thromboembolic complications than chronic atrial fibrillation. Heart failure and systemic hypertension seem to be significant clinical risk factors for stroke in patients with atrial fibrillation, but disagreement persists, and, with few exceptions, subgroups at particular risk have not been convincingly identified. The risk of stroke in persons with thyrotoxic atrial fibrillation seems to be lower than believed previously. Clinical studies have shown that left atrial dilatation is a consequence of the duration of atrial fibrillation rather than a cause, but the relation of left atrial enlargement to stroke is uncertain. Cerebral blood flow may be reduced during atrial fibrillation but seems to increase after cardioversion to sinus rhythm. A high prevalence of silent cerebral infarction has been detected in patients with chronic atrial fibrillation, but there seems to be a low risk of silent cerebral infarction in persons with paroxysmal atrial fibrillation. The one prospective study published to date on stroke prevention in patients with nonrheumatic chronic atrial fibrillation showed that anticoagulation with warfarin significantly reduced the incidence of thromboembolic complications.
The measure of balance in sitting in stroke rehabilitation prognosis.
Authors: Sandin K J , Smith B S
Published: June 2011

To test the hypothesis that recovering stroke patients with initially good sitting balance or those who develop good sitting balance during rehabilitation have better Barthel Index-based functional assessment outcomes than recovering stroke patients with poor sitting balance, we prospectively studied 24 of 25 consecutive stroke patients admitted to a tertiary-care hospital rehabilitation unit. Sitting balance, a prerequisite for most functional activities, was scored using a four-point scale evaluating static and dynamic sitting balance on admission to the rehabilitation unit and weekly until discharge. Functional status was assessed using the Barthel Index 4 or 12 weeks after the stroke. We found a strong positive correlation between Barthel Index score and each weekly sitting balance score. Multiple evaluations over time identified those patients whose sitting balance improved during rehabilitation in our unit; after grouping the patients into those with normal, improved, and poor sitting balance, we found a significant difference in the Barthel Index scores among the three groups. The group of patients whose sitting balance improved had higher Barthel Index scores than the group whose sitting balance did not improve. Ongoing evaluation of sitting balance can be helpful in anticipating functional status at discharge in stroke patients undergoing comprehensive rehabilitation.
Stroke and its modification in Parkinson's disease.
Authors: Struck L K , Rodnitzky R L , Dobson J K
Published: June 2011

Previous studies have not agreed on the incidence of ischemic stroke in persons with Parkinson's disease. There are epidemiologic and neurochemical facets of Parkinson's disease that might confer some benefit or protection against ischemic stroke. We used a case-control method to determine the lifetime history of ischemic stroke in 200 patients with Parkinson's disease and 200 controls of a similar age range. Analysis was also carried out for myocardial infarction as a marker of generalized atherosclerotic disease and for stroke risk factors. The cumulative incidence of ischemic stroke was significantly less in the patients with Parkinson's disease than in the controls, as was the cumulative incidence of myocardial infarction. Among risk factors, significantly fewer patients with Parkinson's disease used tobacco than controls. The decreased incidence of ischemic stroke in the patients with Parkinson's disease appears to be related to their less severe generalized atherosclerosis, possibly due to their lower incidence of tobacco use. In view of the known potential for dopamine to exacerbate experimental ischemic tissue damage, the possibility that the dopamine deficiency in the central nervous system of persons with Parkinson's disease confers an additional specific protective benefit against ischemic stroke cannot be excluded and requires further study.
Acute and long-term changes in serum lipids after acute stroke.
Authors: Woo J , Lam C W , Kay R , Wong H Y , Teoh R , Nicholls M G
Published: June 2011

We studied serum lipid profiles in 171 patients less than or equal to 48 hours after the onset of acute stroke and 3 months later. The 83 patients suffering cerebral infarction had significantly higher serum concentrations of total cholesterol, low density lipoprotein-cholesterol, and apolipoprotein B and significantly lower serum concentrations of triglycerides and lipoprotein (a) less than or equal to 48 hours after ictus than 3 months later. The lipid profiles of the 53 patients suffering lacunar infarction were similar on both occasions, the only significant differences being higher total cholesterol and low density lipoprotein-cholesterol concentrations less than or equal to 48 hours after ictus. No significant changes were observed among the 35 patients suffering cerebral hemorrhage apart from a significantly higher concentration of high density lipoprotein3-cholesterol less than or equal to 48 hours after ictus. Our study, with many patients classified according to stroke subtype, gives results different from those of previous studies with much fewer patients. We conclude that in studies of serum lipid and lipoprotein concentrations as risk factors for cerebral infarction, comparing values obtained less than or equal to 48 hours after admission with control values may incorrectly identify certain lipid fractions as risk factors.
Progressive shrinkage of the thalamus following middle cerebral artery occlusion in rats.
Authors: Fujie W , Kirino T , Tomukai N , Iwasawa T , Tamura A
Published: June 2011

Permanent middle cerebral artery occlusion in rats results in infarction in the ipsilateral cortex and caudate nucleus-putamen. In this ischemia model, severe shrinkage of the ipsilateral half of the thalamus was observed several months after surgery. We examined the serial profile of this phenomenon in 40 rats at intervals from 2 weeks to 6 months after the operation. The area of the ipsilateral half of the thalamus as a percentage of the area of the contralateral half was 87% at 2 weeks, 77% at 1 month, 54% at 3 months, and 54% at 6 months. Such severe morphologic change distant from the original ischemic focus has not been reported in models of experimental focal ischemia. Retrograde degeneration is thought to play an important role in this phenomenon.
Etiologic importance of the intimal flap of the external carotid artery in the development of postcarotid endarterectomy stroke.
Authors: Moore W S , Martello J Y , Quiñones-Baldrich W J , Ahn S S
Published: June 2011

A technically unsatisfactory end point (transition from the removed diseased plaque to normal distal intima) leading to an intimal flap of the external carotid artery has been identified as a source of perioperative stroke. The mechanism involves thrombus formation with retrograde propagation of the thrombus and subsequent embolization of the internal carotid artery. This report describes three cases illustrating this mechanism and methods of identification and correction. This mechanism of postoperative stroke adds further justification for the routine use of intraoperative surveillance studies to document the technical result of endarterectomy involving the internal and external carotid arteries. When an unsatisfactory end point is identified in the external carotid artery, it should be corrected with the same sense of concern as a similar finding in the internal carotid artery.
Regression of intracardiac thrombus after embolic stroke.
Authors: Yasaka M , Yamaguchi T , Miyashita T , Tsuchiya T
Published: June 2011

Using two-dimensional echocardiography, we studied the pathophysiology of intracardiac thrombus regression accompanied by anticoagulant therapy in 82 consecutive patients with acute cardiogenic cerebral embolism. We noted intracardiac thrombus in 15 patients; nine of the 15 were started on anticoagulant therapy with warfarin potassium to maintain the prothrombin time between 2.5 and 3.5 (international normalized ratio). Serial two-dimensional echocardiograms were obtained for these nine patients before and after anticoagulation, with the plasma levels of fibrinopeptide A, fibrinopeptide B beta 15-42, and D-dimer measured at the same time. In eight of the nine patients the intracardiac thrombi gradually decreased in size while the plasma level of fibrinopeptide A fell to within the normal range and the plasma levels of fibrinopeptide B beta 15-42 and D-dimer remained above the normal ranges. In the other patient the thrombus disappeared, with embolization to the right arm immediately after starting anticoagulant therapy. Mobile or small thrombi regressed earlier than nonmobile or large ones. We conclude that regression of intracardiac thrombi after anticoagulation may be based on the relative predominance of plasma fibrinolytic activity over anticoagulation-inhibited thrombin activity.
Surgical experience with cerebral amyloid angiopathy.
Authors: Greene G M , Godersky J C , Biller J , Hart M N , Adams H P
Published: June 2011

Cerebral amyloid angiopathy can present as lobar intracerebral hemorrhage in an elderly person, presumably due to increased fragility of the vessels affected by amyloid deposition. For this reason, patients presenting with intracerebral hemorrhage and suspected of having cerebral amyloid angiopathy have often been treated nonsurgically. Since 1983 we have evaluated 11 patients with cerebral amyloid angiopathy (nine women and two men, mean age 73 years) who have undergone either intracerebral hematoma evacuation or brain biopsy. Nine of the 11 patients presented with intracerebral hemorrhage, which was unilobar in three patients and multilobar in six and involved the parietal lobes seven times, the frontal lobes four times, the temporal lobes four times, and the occipital lobes twice. These nine patients underwent hematoma removal, with no cases of abnormal intraoperative bleeding or recurrent hemorrhage. Six patients improved neurologically, and two were unchanged after hematoma evacuation; the remaining patient had a fatal cardiopulmonary arrest during the immediate postoperative period. During follow-up in seven patients (median 11 months, range 1 week to 74 months) none experienced a recurrent intracerebral hemorrhage and four continued to improve. Two of the 11 patients had cerebral amyloid angiopathy diagnosed by brain biopsy as part of an evaluation for dementia, also without surgical complications. This series suggests that patients with cerebral amyloid angiopathy may safely undergo operative procedures, and patients presenting with intracerebral hemorrhage may show neurologic improvement following evacuation of the hematoma.
Comparison of transcranial and cervical continuous-wave Doppler in the evaluation of intracranial collateral circulation.
Authors: Bass A , Krupski W C , Dilley R B , Bernstein E F , Otis S M
Published: June 2011

Adequate intracranial collateral circulation reduces risk of stroke in carotid artery surgery. To evaluate their relative accuracies in assessing intracranial collateral blood flow, we prospectively compared transcranial Doppler and continuous-wave Doppler of the cervical carotid arteries combined with compression of the common carotid artery in 28 consecutive patients before carotid endarterectomy. Ten healthy volunteers served as controls. Three patients (11%) were excluded from compression of arteries because of diffuse disease in the common carotid artery. A total of 199 compressions were performed without complications. Lack of a suitable transtemporal window precluded the performance of transcranial Doppler in three patients (12%). The anterior communicating artery was identified in all the normal volunteers and 80% of patients by both methods. The posterior communicating artery was identified by both methods in 16 of 20 attempts in controls. Continuous-wave Doppler identified the posterior communicating artery in 30 of 50 attempts in patients; transcranial Doppler identified the posterior communicating artery in 20 of 44 attempts in patients (p greater than 0.5). Detection of intracranial collaterals correlated with intraoperative carotid artery back pressure measurements in 23 of 25 patients (92%). We conclude that continuous-wave Doppler of the extracranial arteries combined with common carotid artery compression is a safe and easy way to detect intracranial collaterals, with an accuracy equivalent to transcranial Doppler.
Effect of intra-arterial tissue plasminogen activator and urokinase on autologous arterial emboli in the cerebral circulation of rabbits [corrected].
Authors: Benes V , Zabramski J M , Boston M , Puca A , Spetzler R F
Published: June 2011

We conducted a randomized, blinded controlled trial to test the efficacy of fibrinolytic therapy with tissue plasminogen activator and urokinase in the treatment of acute embolic stroke. Embolic stroke was simulated in rabbits by injecting three 0.5 x 0.5 mm fragments of autologous arterial thrombus harvested from a traumatized auricular artery. Thirty minutes after embolization the rabbits were blindly treated with tissue plasminogen activator (n = 21), urokinase (n = 20), or 0.9% saline (n = 20). At 6 hours the rabbits were sacrificed, and the cerebral vasculature was inspected for the location and number of emboli. The brain was then cut into 0.5-cm-thick coronal sections and stained with triphenyltetrazolium chloride to define areas of infarction. Treatment with either tissue plasminogen activator or urokinase significantly reduced the number of emboli present in the cerebral circulation (p less than 0.05). The area of ischemic injury was also significantly reduced (p less than 0.05) by acute fibrinolytic therapy with either tissue plasminogen activator or urokinase. However, only treatment with tissue plasminogen activator significantly reduced (p less than 0.05) the incidence of infarction. There was no evidence of intracerebral hemorrhage in any rabbit. Early fibrinolytic therapy improved outcome in this model of acute embolic stroke.
Moderate hypothermia after cardiac arrest of 17 minutes in dogs. Effect on cerebral and cardiac outcome.
Authors: Leonov Y , Sterz F , Safar P , Radovsky A
Published: June 2011

Moderate hypothermia (30 degrees C) induced before circulatory arrest is known to improve neurologic outcome. We explored, for the first time in a reproducible dog outcome model, moderate hypothermia induced during reperfusion after cardiac arrest (resuscitation). In three groups of six dogs each (N = 18), normothermic ventricular fibrillation cardiac arrest (no blood flow) of 17 minutes was reversed by cardiopulmonary bypass--normothermic in control group I (37.5 degrees C) and hypothermic to 3 hours in groups II (32 degrees C) and III (28 degrees C). Defibrillation was achieved in less than or equal to 5 minutes and partial bypass was continued to 4 hours, controlled ventilation to 20 hours, and intensive care to 96 hours. All 18 dogs survived. Electroencephalographic activity returned significantly earlier in groups II and III. Mean +/- SD best neurologic deficit between 48 and 96 hours was 44 +/- 8% in group I, 38 +/- 12% in group II, and 35 +/- 7% in group III (differences not significant). Best overall performance category 2 (good outcome) between 48 and 96 hours was achieved in none of the six dogs in group I and in four of the 12 dogs in the combined hypothermic groups II and III (difference not significant). Mean +/- SD brain total histologic damage score was 130 +/- 22 in group I, 93 +/- 28 in group II (p = 0.05), and 80 +/- 26 in group III (p = 0.03). Gross myocardial damage was greater in groups II and III than in group I--numerically higher overall and significantly higher in group III for the right ventricle alone (p = 0.02). Moderate hypothermia after prolonged cardiac arrest may or may not improve cerebral outcome slightly and can worsen myocardial damage.
Effect of ischemia induced by middle cerebral artery occlusion on superoxide dismutase activity in rat brain.
Authors: Michowiz S D , Melamed E , Pikarsky E , Rappaport Z H
Published: June 2011

Acute cerebral ischemia increases the generation of free radicals, causing cell damage, and theoretically may decrease the activity of the scavenging enzyme superoxide dismutase. To investigate the role of superoxide dismutase in cerebral ischemia, we used a model of middle cerebral artery occlusion in rats. In this model an infarct is produced in the pyriform and frontoparietal cortices, extending into the lateral basal ganglia. We measured superoxide dismutase activity by using the xanthine oxidase cytochrome c reduction assay in these areas of rat brains. Tissue samples were analyzed 20 minutes, 2, 6, or 24 hours, or 7 days after middle cerebral artery occlusion and 2 or 24 hours or 7 days after sham operation (n = 8-10 at each time). There was no significant change in superoxide dismutase activity relative to control values in any brain area at any time up to 24 hours after surgery. However, 7 days after middle cerebral artery occlusion a significant decline in superoxide dismutase activity, to 55%-68% (p less than 0.05) of that in unoperated controls, was observed in all brain areas. Our results do not support an important role for changes in the activity of endogenous superoxide dismutase during the acute phase of cerebral ischemia. However, the decrease in superoxide dismutase activity 7 days after ischemia could indicate ongoing additional damage to peri-infarct tissue.
Giant basilar aneurysm in the course of subacute bacterial endocarditis.
Authors: Calopa M , Rubio F , Aguilar M , Peres J
Published: June 2011

We describe a man aged 42 years with mitral valve regurgitation who suffered from subacute bacterial endocarditis caused by Streptococcus morbillorum. The clinical picture began with a toxic syndrome. Five months later, the patient had an embolic episode and a right rostral pontine stroke, which was followed a few days later by an adversive focal seizure on the right. Despite antibiotic treatment, he suffered complete third nerve palsy. Arteriography, magnetic resonance imaging, and computed tomography of the brain showed a giant aneurysm in the rostral end of the basilar artery; the aneurysm was clipped. We discuss the clinical features, radiology, and characteristics of this aneurysm as a unique case of a giant bacterial aneurysm in the vertebrobasilar system.
Coagulation-fibrinolysis abnormalities in acute and chronic phases of cerebral thrombosis and embolism.
Authors: Tohgi H , Kawashima M , Tamura K , Suzuki H
Published: June 2011

We assayed plasma concentrations of fibrinogen, fibrinopeptide A, plasmin-alpha 2 plasmin inhibitor complex, D dimer, and antithrombin III activity in 40 patients with cerebral thrombosis and nine patients with cerebral embolism during the acute (less than 7 days), subacute (7-27 days), and chronic (greater than or equal to 28 days) periods and compared these with 69 controls. In cerebral thrombosis, fibrinogen and fibrinopeptide A levels were elevated significantly in all stages (p less than 0.001), whereas plasmin-alpha 2 plasmin inhibitor complex and D dimer levels were elevated significantly in the subacute and chronic periods. The antithrombin III activity was significantly decreased in the acute stage. The elevation of fibrinogen and plasmin-alpha 2 plasmin inhibitor complex levels in the acute stage was significantly greater in patients with an infarct size greater than 10 mm2 compared to patients with an infarct size less than 10 mm2. We observed similar changes in patients with cerebral embolism. These results suggest that enhanced coagulation exists at all stages and endogenous fibrinolysis is activated in the subacute and chronic periods in a large proportion of patients with cerebral thrombosis and embolism.
Temperature modulation of ischemic neuronal death and inhibition of calcium/calmodulin-dependent protein kinase II in gerbils.
Authors: Churn S B , Taft W C , Billingsley M S , Blair R E , DeLorenzo R J
Published: June 2011

We used brief bilateral carotid artery occlusion in gerbils to examine the effects of temperature on ischemia-induced inhibition of calcium/calmodulin-dependent protein kinase II activity and neuronal death. In normothermic (36 degrees C) gerbils, ischemia induced a severe loss of hippocampal CA1 pyramidal neurons measured 7 days after ischemia (28.4 neurons/mm, n = 10; control density in 10 naive gerbils 262.1 neurons/mm) and a significant decrease in forebrain calcium/calmodulin-dependent protein kinase II autophosphorylation measured 2 hours after ischemia (12.9 fmol/min, n = 6; control phosphorylation in six naive gerbils 23.5 fmol/min). The effect of temperature on these indicators of ischemic damage was examined by adjusting intracerebral temperature before and during the ischemic insult. Hyperthermic (39 degrees C) gerbils showed almost complete loss of neurons in the CA1 region (3.0 neurons/mm, n = 11) and extension of neuronal death into the CA2, CA3, and CA4 regions. In addition, hyperthermia exacerbated ischemia-induced inhibition of calcium/calmodulin-dependent protein kinase II activity (4.2 fmol/min, n = 6). Hypothermia (32 degrees C) protected against ischemia-induced CA1 pyramidal cell damage (257.0 neurons/mm, n = 20) and inhibition of calcium/calmodulin-dependent protein kinase II activity (26.0 fmol/min, n = 6). Our results are consistent with the hypothesis that loss of calcium/calmodulin-dependent protein kinase II activity may be a critical event in the development of ischemia-induced cell death.
Sensory ataxic hemiparesis in thalamic hemorrhage.
Authors: Dobato J L , Villanueva J A , Giménez-Roldán S
Published: June 2011

Ataxic hemiparesis with cerebellar-like features has been reported following infarction or hemorrhage of the thalamus. We describe five patients with incoordination and corticospinal tract signs in the limbs opposite a dorsolateral thalamic hemorrhage. In four patients the hemorrhage extended superiorly into the lateral ventricle, the adjacent paraventricular region, and the upper and medial parts of the posterior limb of the internal capsule. Instead of cerebellar dysfunction, these patients exhibited directional errors of movement that improved distinctly when performed under visual guidance. We explain the incoordination on the basis of conscious deep sensory loss in the involved limbs. Perception of light touch, painful pinprick, and temperature were preserved in all patients. We use the term "sensory ataxic hemiparesis" to distinguish these patients from those with "classic" ataxic hemiparesis and cerebellar-like features, a distinction that may be important when planning functional rehabilitation.
Histologic assessment of neurons in rat models of cerebral ischemia.
Authors: Eke A , Conger K A , Anderson M , Garcia J H
Published: June 2011

We describe a method for typing neurons into four progressive stages of ischemic deterioration based on visual characterization of the nucleus in terms of its optical contrast, delineation along the nuclear-cytoplasmic interface, and its shape. Difficulty in assessing nuclear shape required the introduction of an angularity comparator chart to improve the investigator's accuracy. Three investigators typed neurons obtained from normal, ischemic, and ischemic-reperfused rat brains. Accuracy and reproducibility of the investigators' typing decisions with and without the angularity comparator charts were evaluated. The accuracy of subjective shape assessment was compared with objective digitizer measurements of the same. The angularity comparator charts reduced subjective shape classification error by two thirds, and group error (overall performance expressed by the coefficient of variance) decreased from 15.9% to 4.7% for Type I (normal cells), from 33.9% to 17.3% for Type II (cells with angular nuclei), from 15.5% to 14.1% for Type III (cells with smeared nuclei), and from 3.2% to 5.5% for Type IV (dead cells). Thus, Type I and IV neurons can be assessed at a higher reproducibility than the intermediate Types II and III. Our typing method can also be used to evaluate the effect of treatment regimes on ischemic neuronal damage.
Immunohistochemical characterization of cerebrovascular amyloid in 46 autopsied cases using antibodies to beta protein and cystatin C.
Authors: Maruyama K , Ikeda S , Ishihara T , Allsop D , Yanagisawa N
Published: June 2011

Using immunohistochemical staining methods with antibodies to amyloid beta protein and human cystatin C, we examined cerebrovascular amyloid protein in the brains from 46 cases with cerebral amyloid angiopathy (seven with Alzheimer's disease, one with Down's syndrome, 18 with intracranial hemorrhage, 10 with cerebral infarction, and 10 elderly patients without any neurologic disorder). All cerebrovascular amyloid deposits in these 46 cases were consistently immunoreactive to anti-beta protein antibody. However, in nine cases some vascular walls with strong beta protein immunoreactivity also reacted less intensely with the anti-cystatin C antiserum. Of these nine cases, seven showed relatively heavy cerebrovascular amyloid deposition, and all seven had suffered a fatal subcortical hemorrhage presumably caused by cerebral amyloid angiopathy. Previous limited studies have suggested that the amyloid protein seen in elderly individuals with cerebral amyloid angiopathy is composed of beta protein. However, subcortical hemorrhage rarely occurs in such individuals. Our study shows that aged patients with different brain disorders commonly suffer from beta protein-type cerebral amyloid angiopathy, and we also suggest that the severity of beta protein-type cerebrovascular amyloid deposition is a fundamental factor in cerebral amyloid angiopathy-induced brain hemorrhage in the elderly. The nature of the cystatin C-immunoreactive substance in some of these vascular lesions is uncertain, but it might conceivably play an additional important role in the pathogenesis of brain hemorrhage in these cases.
Effect of plasma glucose concentration on cerebral metabolism during partial ischemia in neonatal piglets.
Authors: Laptook A R , Corbett R J , Nunnally R L
Published: June 2011

We used neonatal piglets to determine the influence of plasma glucose concentration on cerebral energy metabolism during and immediately after partial ischemia. We assessed cerebral metabolism using in vivo phosphorus-31 magnetic resonance spectroscopy. Arterial plasma glucose concentration was increased in four piglets by systemic infusions of dextrose in water for comparison with infusions of saline in four controls or decreased in eight piglets by fasting for 24-48 hours for comparison with four fed piglets. Plasma glucose concentration showed a significant linear correlation with intracellular pH (r = -0.7, p less than 0.05). Piglets that developed hypoglycemia during partial ischemia had a smaller reduction in intracellular pH and a larger increase in inorganic phosphate content than piglets that were normoglycemic or hyperglycemic during ischemia. Similar differences persisted during the first 5 minutes of postischemic reperfusion. Subsequently, the cerebral concentrations of phosphorylated compounds returned to normal in all piglets. Our results demonstrate that 1) arterial plasma glucose concentration influences cerebral energy metabolism and intracellular pH during ischemia, 2) neonatal piglets can develop profound brain acidosis, and 3) brain acidosis during ischemia does not influence the restoration of cerebral phosphorylated compounds to control levels during the first 90 minutes after ischemia.
Effect of endothelin on cortical microvascular perfusion in rats.
Authors: Willette R N , Sauermelch C , Ezekiel M , Feuerstein G , Ohlstein E H
Published: June 2011

We used laser-Doppler flowmetry to study the effects of endothelin-1 on local cortical microvascular perfusion and resistance in 29 pentobarbital-anesthetized rats. Intravenous administration of 10-300 pmol endothelin-1 reduced arterial blood pressure and microvascular resistance and increased microvascular perfusion. However, intracarotid administration of low doses of endothelin-1 increased microvascular perfusion and reduced microvascular resistance and arterial blood pressure, whereas high doses (greater than or equal to 300 pmol) reduced microvascular perfusion and increased microvascular resistance and arterial blood pressure. Only the high dose/low flow response was associated with attenuation of the electrocorticogram. The low dose/high flow and high dose/low flow responses to endothelin-1 were not altered by blockade of muscarinic and adrenergic receptors. In addition, systemic metabolic changes (arterial pH, PaCO2, PaO2, and plasma glucose concentration) did not account for the cerebrovascular effects of endothelin-1. Platelet hyperaggregability also did not appear to be a causative factor in the high dose/low flow response to endothelin-1. In fact, ex vivo rat platelet aggregation was inhibited by intracarotid administration of 300 pmol endothelin-1. In conclusion, the cerebral vasculature exhibits extreme sensitivity to the vasodilator properties of endothelin-1 at low doses. The ischemic vasoconstrictor effects observed at high doses implicate endothelin-1 as an important mediator of cerebral vasospasm and/or postischemic hypoperfusion.
Chronic cerebral intracellular alkalosis following forebrain ischemic insult in rats.
Authors: Chopp M , Vande Linde A M , Chen H , Knight R , Helpern J A , Welch K M
Published: June 2011

We measured cerebral intracellular pH using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy during 1 week after forebrain ischemia or sham operation in eight and seven rats, respectively. Mean maximum pH was significantly higher (p less than 0.003) in the ischemic group than in the sham-operated group (7.34 +/- 0.03 and 7.19 +/- 0.02, respectively). The difference between mean maximum pH and baseline pH (7.08 +/- 0.01 in each group) was significantly greater (p less than 0.02) in the ischemic group than in the sham-operated group. In the ischemic group, alkalosis occurred primarily after 48-72 hours of recirculation. We speculate that brain tissue alkalosis occurring chronically after ischemia is associated with delayed ischemic neuronal death.
Impairment of metabolic recovery with increasing periods of middle cerebral artery occlusion in rats.
Authors: Selman W R , Crumrine R C , Ricci A J , LaManna J C , Ratcheson R A , Lust W D
Published: June 2011

We examined the consequences of reflow on metabolic recovery following increasing periods of focal ischemia. The middle cerebral artery of 21 Sprague-Dawley rats was occluded with a snare ligature for 1, 2, or 6 hours followed by 5, 4, or 0 hours of reflow, respectively (seven rats in each group). All animals were injected with neutral red for visual confirmation that the affected regions were reperfused. The brains were frozen in situ, and the concentrations of adenosine triphosphate, phosphocreatine, glycogen, and lactate were determined in those areas corresponding to the normally perfused medial ipsilateral cortex, the perifocal region, and the ischemic focus. Values for the 6 hours' occlusion with no reflow group served as a control to demonstrate restoration of metabolite concentrations. In both groups with reflow, the levels of high-energy phosphates were greater than control, but this effect of reflow was primarily significant for the group with 1 hour's occlusion (p less than 0.05). The levels of glycogen and lactate provided additional evidence that the extent of metabolite restoration was graded; following 2 hours of occlusion, metabolite recovery was compromised (p less than 0.05). Our data strongly support the concept that the window of opportunity for effective treatment of focal ischemia by reperfusion is narrow (of short duration).