The proteome of mouse cerebral arteries

The cerebral vasculature ensures proper cerebral function by transporting oxygen, nutrients, and other substances to the brain. Distribution of oxygenated blood throughout the neuroaxis takes place at the level of the circle of Willis (CW). While morphologic and functional alterations in CW arteries and its main branches have been reported in cerebrovascular and neurodegenerative diseases, accompanying changes in protein expression profiles remain largely uncharacterized. In this study, we performed proteomics to compile a novel list of proteins present in mouse CW arteries and its ramifications. Circle of Willis arteries were surgically removed from 6-month-old wild-type mice, proteins extracted and analyzed by two proteomics approaches, gel-free nanoLC-mass spectrometry (MS)/MS and gel-based GelLC-MS/MS, using nanoAcquity UPLC coupled with ESI-LTQ Orbitrap XL. The two approaches helped maximize arterial proteome coverage. Six biologic and two technical replicates were performed. In all, 2,188 proteins with at least 2 unique high-scoring peptides were identified (6,630 proteins total). Proteins were classified according to vasoactivity, blood–brain barrier specificity, tight junction and adhesion molecules, membrane transporters/channels, and extracellular matrix/basal lamina proteins. Furthermore, we compared the identified CW arterial proteome with the published brain microvascular proteome. Our database provides a vital resource for the study of CW cerebral arterial protein expression profiles in health and disease.     

Evaluation of cross-circulation through circle of Willis using an ultrasonic Doppler technique. Part I. Comparison between blood flow velocity by ultrasonic Doppler flowmetry and angiogram

In 24 patients with cerebrovascular disease and 6 without organic brain lesions, the increased velocity of blood flow in both the internal carotid and vertebral arteries during a contralateral carotid compression was compared with the angiographic appearance of the circle of Willis. The flow velocity was measured using ultrasonic Doppler flowmetry. It was not possible to investigate fully the relationship between the increase of velocity of blood flow in the internal carotid artery and the anatomical variations of the circle of Willis, specifically the anterior cerebral and communicating arteries. The velocity of flow in the patients with an aplastic proximal portion of the anterior cerebral artery showed no increase. There were no differences in the increase of velocity of flow in the vertebral artery in patients with hypoplastic, normal and fetal posterior communicating arteries. It is considered that although anatomical variations of the circle vessels influence the cross-circulation via the circle of Willis, peripheral vascular factors distal to the circle also play an important role in the quantity of cross-circulation through the circle.     

A model of the cerebral and cerebrospinal fluid circulations to examine asymmetry in cerebrovascular reactivity.

The authors examined the steal phenomenon using a new mathematical model of cerebral blood flow and the cerebrospinal fluid circulation. In this model, the two hemispheres are connected through the circle of Willis by an anterior communicating artery (ACoA) of varying size. The right hemisphere has no cerebrovascular reactivity and the left is normally reactive. The authors studied the asymmetry of hemispheric blood flow in response to simulated changes in arterial blood pressure and carbon dioxide concentration. The hemispheric blood flow was dependent on the local regulatory capacity but not on the size of the ACoA. Flow through the ACoA and carotid artery was strongly dependent on the size of the communicating artery. A global interhemispheric "steal effect" was demonstrated to be unlikely to occur in subjects with nonstenosed carotid arteries. Vasoreactive effects on intracranial pressure had a major influence on the circulation in both hemispheres, provoking additional changes in blood flow on the nonregulating side. A method for the quantification of the crosscirculatory capacity has been proposed.     

Magnetic resonance evaluation of the cerebral circulation in obstructive arterial disease

BACKGROUND: The aim of the current overview is to highlight the possibilities of magnetic resonance imaging (MRI) in the assessment of patients with obstructive arterial disease. The anatomic and hemodynamic aspects of the extra- and intracranial cerebral circulation were analyzed and show the importance of combining both aspects in studying cerebral hemodynamic changes. RESULTS: Three levels of cerebral circulation are distinguished: blood flow to the brain (level 1); the distribution of blood flow in the brain (level 2), and finally perfusion of the brain (level 3). To investigate the anatomy of the arteries in the neck and the circle of Willis, contrast-enhanced, time-of-flight and phase contrast MR angiography (MRA) are available. To evaluate the hemodynamics at the 1st and 2nd level of the cerebral circulation two-dimensional phase contrast (volume flow and flow direction) MRA can be used. In addition, the distribution of blood via the circle of Willis can be visualized with dynamic MRA. At the 3rd level, measurements of regional brain perfusion can be obtained by injecting gadolinium, dynamic susceptibility contrast MRI, or noninvasively with arterial spin labeling (ASL) MRI. In addition, selective ASL MRI is able to evaluate the perfused territories of individual brain-feeding arteries. CONCLUSION: The currently available MR techniques allow evaluation of the cerebral circulation from the aortic arch upwards towards the microvasculature and brain tissue perfusion in a comprehensive 20-min protocol. The combined use of the described MR methods in patients with steno-occlusive disease will further clarify the pathophysiological relations between the vasculature, perfusion and brain function.     

Cerebral hemodynamics in relation to patterns of collateral flow.

BACKGROUND AND PURPOSE: We sought to investigate the relation between collateral flow via different pathways and hemodynamic parameters measured by dynamic susceptibility contrast-enhanced MRI in patients with severe carotid artery disease. METHODS: Dynamic susceptibility contrast-enhanced MRI was performed in 66 patients and 33 control subjects. Patients had severe stenosis (>70%, n=12), unilateral occlusion (n=38), or bilateral occlusion (n=16) of the internal carotid artery (ICA). Cerebripetal flow and collateral flow via the circle of Willis were investigated with MR angiography. Collateral flow via the ophthalmic artery was investigated with transcranial Doppler sonography. RESULTS: Patients with ICA stenosis had well-preserved cerebral perfusion and were in general not dependent on collateral supply. Patients with unilateral ICA occlusion had impaired cerebral perfusion. However, appearance time, peak time, and mean transit time in white matter were less increased in patients with than in patients without collateral flow via the circle of Willis (P<0.05). Furthermore, patients with collateral flow via both anterior and posterior communicating arteries had less increased regional cerebral blood volume than patients with collateral flow via the posterior communicating artery only (P<0.05). Patients with bilateral ICA occlusion had severely compromised hemodynamic status despite recruitment of collateral supply. CONCLUSIONS: In patients with unilateral ICA occlusion, the pattern of collateral supply has significant influence on hemodynamic status. Collateral flow via the anterior communicating artery is a sign of well-preserved hemodynamic status, whereas no collateral flow via the circle of Willis or flow via only the posterior communicating artery is a sign of deteriorated cerebral perfusion.     

Noninvasive assessment of arterial compliance of human cerebral arteries with short inversion time arterial spin labeling

A noninvasive method of assessing cerebral arterial compliance (AC) is introduced in which arterial spin labeling (ASL) is used to measure changes in arterial blood volume (aBV) occurring within the cardiac cycle. Short inversion time pulsed ASL (PASL) was performed in healthy volunteers with inversion times ranging from 250 to 850 ms. A model of the arterial input function was used to obtain the cerebral aBV. Results indicate that aBV depends on the cardiac phase of the arteries in the imaging volume. Cerebral AC, estimated from aBV and brachial blood pressure measured noninvasively in systole and diastole, was assessed in the flow territories of the basal cerebral arteries originating from the circle of Willis: right and left middle cerebral arteries (RMCA and LMCA), right and left posterior cerebral arteries (RPCA and LPCA), and the anterior cerebral artery (ACA). Group average AC values calculated for the RMCA, LMCA, ACA, RPCA, and LPCA were 0.56%±0.2%, 0.50%±0.3%, 0.4%±0.2%, 1.1%±0.5%, and 1.1%±0.3% per mm Hg, respectively. The current experiment has shown the feasibility of measuring AC of cerebral arteries with short inversion time PASL.     

Collateral configuration of the circle of Willis: transcranial color-coded duplex ultrasonography and comparison with postmortem anatomy

BACKGROUND AND PURPOSE: The anterior communicating artery (AcoA) and posterior communicating arteries (PcoA) of the circle of Willis provide the main route for collateral blood flow in cases of carotid artery obstruction. Transcranial color-coded duplex ultrasonography (TCCD) allows real-time measurement of the collateral function of the AcoA and PcoA. The primary objective of this study was to determine the collateral artery threshold diameters for supplying collateral flow. METHODS: In 12 acute stroke patients with a median age of 75 years (51 to 91 years), the collateral integrity of the circle of Willis as assessed by TCCD and carotid compression tests was compared with their postmortem anatomy. The lengths and diameters of the collateral arteries were measured. RESULTS: TCCD demonstrated absent anterior collateral flow in 3 patients. In 1 of these patients, absence of anterior cross-flow was due to an occluded anterior cerebral artery, which was revealed at autopsy. Absent posterior collateral flow was found in 14 hemispheres. In 2 of these hemispheres, autopsy revealed a fetal configuration of the posterior cerebral artery hampering posterior collateral flow. The median (range) diameters as found at autopsy of the functional (n=19) and nonfunctional (n=16) collateral arteries of the circle of Willis were 1.1 (0.4 to 2.0) and 0.5 (0.3 to 0.7) mm, respectively (P=0.003). PcoA diameters were found to correlate negatively (rho=-0. 50, P=0.01) to the diameters of their accessory P1 segments. CONCLUSIONS: The threshold diameter allowing for cross-flow through the primary collateral arteries of the circle of Willis is between 0. 4 and 0.6 mm.     

Circle of Willis collateral flow investigated by magnetic resonance angiography

BACKGROUND AND PURPOSE: The circle of Willis (CW) is considered an important collateral pathway in maintaining adequate cerebral blood flow in patients with internal carotid artery (ICA) obstruction. We aimed to investigate the anatomic variation of the CW in patients with severe symptomatic carotid obstructive disease and to analyze diameter changes of its components in relation to varying grades of ICA obstruction and in relation to the presence or absence of (retrograde) collateral flow. METHODS: Seventy-five patients with minor disabling neurological deficits and with ICA stenoses or occlusions were categorized into 4 groups according to the severity of ICA obstruction. This patient population reflected a relatively favorable subgroup of cerebral infarction (considering their minor neurological deficits). All subjects underwent magnetic resonance angiography, including magnetic resonance angiography sensitive to flow direction. CW morphology and the size of its components were determined and compared with those values in control subjects (n=100). RESULTS: Compared with control subjects, patients demonstrated a significantly higher percentage of entirely complete CW configurations (55% versus 36%, P=0.02), complete anterior configurations (88% versus 68%, P=0.002), and complete posterior CW configurations (63% versus 47%, P=0.04). Patients with severe ICA stenosis did not show significantly increased CW vessel diameters. Patients with ICA occlusion demonstrated a high prevalence of collateral flow through the anterior CW and significantly increased diameters of the communicating channels. Patients with bilateral ICA occlusion relied on collateral flow via the posterior CW and demonstrated a bilateral increase in posterior communicating artery diameters (P<0.05). CONCLUSIONS: The anatomic and functional configuration of the CW reflects the degree of ICA obstruction.     

Origin of temperature changes evoked in the brain by sensory stimulation

Temperature was measured in lateral geniculate nucleus, ventrobasal thalamus and inferior colliculus and at the cerebral arteries which supply these structures in monkeys and cats with chronically implanted thermocouples. Animals were studied when they were conscious and when they were anesthetized, during spontaneously occurring changes in behavior and during the presentation of visual, somesthetic, and auditory stimuli. Parallel low-gain and high-gain recorders allowed absolute temperatures to be determined with an accuracy of 0.05 C and temperature changes of 0.0004 C to be resolved. In confirmation of earlier studies, we found that in behaving animals, large changes in temperature occur in cerebral arterial blood and throughout the brain during feeding, sleeping, and arousal. Brain temperature shifts follow blood temperature shifts. The cerebral arterial blood at the circle of Willis is cooler than the brain. When sensory stimuli are presented, the usual thermal response is a rise in temperature at the cerebral arteries followed by a smaller rise in brain temperature. The changes in cerebral arterial blood temperature following sensory stimulation ranged from 0.003 C to 0.133 C in lightly anesthetized animals. The temperature changes in lateral geniculate, ventrobasal thalamus, or inferior colliculus ranged from 0 to 0.067 C and followed the blood temperature changes by 7 to 71 sec. Changes in brain temperature never occurred without a previous change in blood temperature. Blood temperature responses to sensory stimulation were larger in awake animals and in light anesthesia than in deeply anesthetized animals. Blood temperature rises were associated with peripheral cranial vasoconstriction, suggesting that the initial thermal response to sensory stimulation is peripheral autonomic activity and decreased peripheral heat loss. Other investigators observing brain temperature changes following sensory stimulation did not measure cerebral arterial blood temperature and concluded that the shifts in brain temperature were due to changes in neuronal metabolism or cerebral blood flow. The results of the present study do not support this conclusion. When cerebral arterial blood temperature and brain temperature are monitored simultaneously, it is evident that the changes in brain temperature elicited by sensory stimulation are produced by changes in temperature of the cerebral arterial blood.     

Microsurgical angioarchitectonics of depth structures of the brain and depth interarterial anastomoses

The paper deals with the investigation studying the localization of a structure and showing the ways of formation of depth interarterial anastomoses of the brain. Three areas of deep interarterial anastomoses are identified, which are characterized by their symmetric pattern and formed by the arteries supplying blood to the deep cerebral structures and which create an epithalamic circle of anastomoses similar to the basal hypothalamic arterial circle of Willis. The existence of depth interarterial anastomoses points to the sole functional significance of depth structures of the brain. Depth epithalamic anastomoses are mechanisms that are responsible for the additional redistribution of blood from different vascular beds when cerebral blood flow is impaired in the depth structures and their presence should be taken into account during neurosurgical interventions.     

Evaluation of brain death by computed tomography

The absence of cerebral circulation and electrocerebral silence have served as an accurate index of irreversible brain death. It is proposed that computed tomography (CT) findings be evaluated as confirmatory criteria of brain death. To this end, CT evaluation of 14 patients satisfying the conventional criteria of brain death was performed. A.CT finding of severe compression or disappearance of the ventricular system, or so-called "brain tamponade", was seen in 7 (50%) of the 14 patients. Enhanced contrast CT, especially dynamic CT, usually distinctly reveals the cerebral vessels whenever the cerebral blood flow is preserved; conversely, the lack of enhanced brain structures, even comparing attenuation values, indicates the absence of cerebral blood flow. In 7 (70%) of 10 patients, however, there was enhanced contrast of vascular brain structures, especially the circle of Willis, major cerebral arteries, choroid plexuses, and venous sinuses. It is suggested that this result is due to the improvement of demonstrability by CT. The usefulness of CT in the confirmation of brain death lies in visualization of the pathological changes associated with a dead brain, such as "brain tamponade", and the lack of enhanced contrast indicating the absence of cerebral blood flow. The latter point is still problematic as angiography revealed an extremely low cerebral blood flow in a few cases of "dead brain" patients. It is recommended that cerebral blood flow in brain death be evaluated by dynamic CT scanning and correlated with other methods of cerebral blood flow determination (e.g., intravenous digital subtraction angiography).     

Collateral variations in circle of willis in atherosclerotic population assessed by means of transcranial color-coded duplex ultrasonography

BACKGROUND AND PURPOSE: Transcranial color-coded duplex ultrasonography combined with common carotid artery (CCA) compression can be used to assess the collateral function of the circle of Willis. The aim of this study was to assess the unknown fraction of hemodynamic functional anterior and posterior communicating arteries (AcoA and PcoA, respectively) in an atherosclerotic population with no cerebrovascular symptoms. METHODS: In 76 patients with a mean age of 61 (35 to 89) years, the blood flow velocity changes in the precommunicating parts (A1 and P1, respectively) of the anterior and posterior cerebral arteries were measured during CCA compression. The AcoA was defined as functional if blood flow was reversed in the ipsilateral A1 and enhanced in the contralateral A1 during CCA compression. The PcoA was defined as functional if the flow velocity in the P1 was enhanced >20% during ipsilateral CCA compression. RESULTS: It was possible to assess cross flow through the anterior part of the circle of Willis in 95% of the subjects. Failure of this collateral pathway was caused by a hypofunctional AcoA in 4% and a hypofunctional A1 in 1% of the subjects. Anomalies in the posterior part of the circle of Willis hampering collateral flow from the basilar to the internal carotid artery were found in 45% of the hemispheres. Thirty-eight percent of PcoAs were hypofunctional, and 7% of the posterior cerebral arteries had a persistent fetal anatomy. CONCLUSIONS: We found that in subjects with no cerebrovascular symptoms, the anterior collateral pathway of the circle of Willis was nearly always functional. In contrast, the posterior collateral pathway was nonfunctional in almost half of the total number of hemispheres. Comparing these basic data with data from patients with cerebral ischemic disease might further help to elucidate the importance of the collateral capacity of the circle of Willis.     

经颅彩色多普勒超声造影在颞骨声窗受限的脑梗死患者颅内侧支循环评价中的应用

目的 探讨经颅彩色多普勒超声造影 （contrast-enhanced transcranial color-coded doppler, CE-TCCD） 技 术在判断颞骨声窗受限的脑梗死及短暂性脑缺血发作 （transient ischemic attack, TIA） 患者颅内侧支 循环方面的应用。 方法 选择由于声窗的限制, 经颅彩色多普勒超声检查未探及颅内血流信号的70例脑梗死及TIA 患者, 应用CE-TCCD检测其颅内血流及Willis环的开放情况, 进一步完善磁共振血管成像 （magnetic resonance angiography, MRA） 后比较两者的诊断结果。 结果 70例患者中男51例, 女19例, 平均年龄 （66.4±11.9） 岁 , CE-TCCD共检出41条交通动脉开放, 其 中38条与MRA诊断一致, 超声造影与MRA诊断一致性好 （Kappa值为0.696, P ＜0.001） 。 超声造影检测 的灵敏度为79.2%, 特异度为91.9%。 结论 在颞骨声窗受限的脑梗死及TIA患者中 , CE-TCCD可用于颅内侧支循环的评价。     

Modelling cerebrovascular circulation from the viewpoint of autoregulation mechanisms

The rationale for cerebral blood flow modelling is to extrapolate the possible effects of the pharmacological agents and significance of different pathologic states. Most authors present linear, statistical models. Such modelling does not take into consideration many important factors. Autoregulation of cerebral circulation is the most important one. It maintains cerebral blood flow on a constant level despite significant changes of systemic pressure. Influence of autoregulation is necessary for evaluation of the different anatomical configurations of the main supplying arteries and the cerebral arterial circle of Willis. This paper presents original, non-linear and dynamic model of the cerebral circulation with factor of autoregulation. Comparison of the data from the modelling and from the clinical observations shows high correlation.     

Cerebral blood flow regulation: vascular resistance adjustments in the circle of Willis.

Continuous measurements of systemic blood pressure (BP), cerebral perfusion pressure and CBF were accomplished in the cat during transient hypertension, hypercapnia and bilateral carotid artery occlusion. From these measurements resistance values in the circle of Willis and in the cerebral arteries distal to the circle were calculated. The results indicate that the arteries of the circle of Willis and the arteries distal to the circle of Willis dilate and contract independently.     

Interaction of cardiovascular disease and neurodegeneration: transcranial Doppler ultrasonography and Alzheimer's disease

OBJECTIVE: Recent post-mortem studies have reported that the severity of atheromatous deposits in the circle of Willis is significantly greater, relative to non-demented (ND) elderly persons, in subjects with neuropathologically diagnosed Alzheimer's disease (AD). Additionally, the severity of intracranial atherosclerosis correlates significantly with the densities of neuritic plaques and neurofibrillary tangles. In this study, we examine the arteries of the circle of Willis by transcranial Doppler (TCD) ultrasonography. METHODS: TCD was used to measure, in 25 AD patients and 30 ND elderly subjects, mean flow velocities and pulsatility indices in 16 different segments of the circle of Willis. The data were compared with and without adjustment for age, gender and systolic blood pressure. RESULTS: The AD patients had systematically higher pulsatility indices (p<0.005) than the ND group. Incremental increases of pulsatility indices in these segments had odds ratios ranging from 1.8 to 48 for the presence of AD when adjusted for age, gender and systolic blood pressure. The left internal carotid artery siphon and the left posterior cerebral artery were the two vessels that were strongly associated with AD diagnosis. Mean flow velocities were generally lower in patients with AD but the differences did not reach the significance level. DISCUSSION: The pulsatility indices of the arteries of AD patients were generally greater than those of similarly-aged ND subjects. This difference is most likely due to increased arterial wall rigidity imposed by atherosclerotic changes. Atherosclerotic disease of intracranial arteries may be a risk factor for AD.     

Trophic changes in the arteries at the base of the rat brain in response to bilateral common carotid ligation

A rat model was developed to examine changes in the posterior circle of Willis and the basilar and intracranial vertebral arteries after bilateral common carotid ligation. This procedure produced a major redistribution of blood to the head, with increased flow through the vertebral and basilar arteries. Changes in the vertebral, basilar, posterior communicating and proximal segments of the posterior cerebral arteries and neck vessels were assessed by postmortem barium sulfate arteriography and by histology of the middle portion of the basilar arteries serially at four days, and one, two, four and 15 weeks post-ligation. The changes noted were basilar and vertebral artery tortuosity, enlargement, and duplication of the vertebro-basilar junction. By 15 weeks, these intracranial vascular changes had largely regressed toward normal, commensurate with the appearance of multiple collateral vessels which were scattered throughout the soft tissues of the neck and shunted the original ligation sites. A mechanism that could explain these trophic vessel changes in response to increased blood flow is discussed. Some possible correlates of these findings with several brain vascular diseases are presented.     

Mechanism of cerebral blood flow augmentation by hemodilution in rabbits.

BACKGROUND AND PURPOSE: Hemodilution is known to increase cerebral blood flow, but it is not known whether the increase in flow is a direct result of a decrease in viscosity or whether it may be due to compensatory vasodilatation in response to the decrease in oxygen carrying capacity that results from hemodilution. This study is designed to investigate this question. METHODS: Changes in regional cerebral blood flow were studied in normal and ischemic brains of 15 and 18 rabbits, respectively. In one group of rabbits graded hemodilution was used to reduce arterial oxygen content progressively in stages; in the second group the arterial oxygen content was reduced in similar stages by progressively larger reductions in the concentration of inspired oxygen (hypoxic hypoxia). In the ischemic animals focal ischemia was produced by embolic occlusion of the right middle cerebral artery. RESULTS: In the normal rabbits, hypoxic hypoxia and hemodilution resulted in similar progressive increases in cerebral blood flow as arterial oxygen content fell. In the ischemic animals, there was a significant fall in cerebral blood flow in the ischemic region in all groups after arterial occlusion. Hemodilution resulted in a progressive increase in cerebral blood flow in both ischemic and nonischemic regions. With hypoxic hypoxia, however, cerebral blood flow in the ischemic region showed no increase or a slight decrease. CONCLUSIONS: Even though hypoxic hypoxia results in a marked increase in cerebral blood flow in normal brain, it does not significantly change cerebral blood flow in ischemic brain. In contrast, hemodilution resulting in a comparable degree of hypoxemia is capable of significantly increasing cerebral blood flow in ischemic brain. Therefore, the mechanism of blood flow augmentation by hemodilution in ischemic brain is probably related to a direct hemorheologic effect rather than to the resulting hypoxemia.     

Cerebral aneurysms and variations in the circle of Willis

In order to obtain information about the relationship between variations in the circle of Willis and aneurysms, 44 complete circles of Willis with aneurysm were studied macroscopically. The incidence of variations was significantly higher in the aneurysm series than in the control circles without aneurysm. There was a definite correlation between asymmetric proximal segments of the anterior cerebral artery and aneurysms of the anterior communicating artery, and a tendency to correlation was found in the case of asymmetric posterior communicating arteries and aneurysms on the internal carotid artery-posterior communicating artery junction. In the light of these findings it seems likely that through hemodynamic changes variation in the circle of Willis plays some role in the development of cerebral aneurysms.     

Occlusion of the MCA by an intraluminal filament may cause disturbances in the hippocampal blood flow due to anomalies of circle of Willis and filament thickness

We examined blood flow changes and histology in the hippocampus induced by occlusion of the middle cerebral artery (MCA) by a filament in Swiss albino and SV-129 mice (n=67) and in Wistar rats (n=64). Filling cerebral arteries with carbon black revealed that one or both posterior communicating arteries were hypoplastic in 50% of Swiss mice. Ischemic changes were detected in the ipsilateral hippocampus with 2,3,5-triphenyl tetrazolium chloride or hematoxylin and eosin staining when these mice were subjected to 2-h MCA occlusion and 22-h reperfusion. No such abnormalities were found in SV-129 mice and Wistar rats (except one). The hippocampal blood flow dropped to 60+/-2.3% of the baseline in mice with a normal circle of Willis but to 37+/-4.2% in those with an incomplete circle when the MCA was occluded with a 6/0 nylon filament. When an 8/0 filament was used, no flow change in mice with a normal circle but a decrease to 60+/-2% in those with an incomplete circle was observed. A flow drop to 63+/-4% was also seen in Wistar rats when a 3/0 filament used. These data demonstrate that occlusion of the MCA by a thick filament may cause flow reduction in the hippocampus, which may be severe enough to lead to infarction if the circle of Willis is anomalous.