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Examines cerebral blood flow measurement. Recognition on the significance of the blood supply to the brain by the Greeks in early times; Elucidation that pressure on the vessels of the neck resulted in anesthesia sufficient to carry out certain surgical procedures; Development of techniques for the examination of the pial vessels; Focus of scientific investigations on the physiological aspects of the brain blood supply.

The anterior cerebral artery (ACA) and the anterior communicating artery (AComA) are important arteries of the telencephalon and are prominent location for cerebral aneurysms. Their embryological development is closely linked, and explains the possible variants seen in adults. In this paper, we present details related to the development of these two arteries, focusing on some variants such as the infra-optic course of the ACA, the unpaired ACA, and the persistent primitive olfactory artery. [ABSTRACT FROM AUTHOR]

Careful examination of relevant literature shows that many of the most cherished concepts of the blood-brain barrier are incorrect. These include an almost mythological belief in its immaturity that is unfortunately often equated with absence or at least leakiness in the embryo and fetus. The original concept of a blood-brain barrier is often attributed to Ehrlich; however, he did not accept that permeability of cerebral vessels was different from other organs. Goldmann is often credited with the first experiments showing dye (trypan blue) exclusion from the brain when injected systemically, but not when injected directly into it. Rarely cited are earlier experiments of Bouffard and of Franke who showed methylene blue and trypan red stained all tissues except the brain. The term "blood-brain barrier" "Blut-Hirnschranke" is often attributed to Lewandowsky, but it does not appear in his papers. The first person to use this term seems to be Stern in the early 1920s. Studies in embryos by Stern and colleagues, Weed and Wislocki showed results similar to those in adult animals. These were well-conducted experiments made a century ago, thus the persistence of a belief in barrier immaturity is puzzling. As discussed in this review, evidence for this belief, is of poor experimental quality, often misinterpreted and often not properly cited. The functional state of blood-brain barrier mechanisms in the fetus is an important biological phenomenon with implications for normal brain development. It is also important for clinicians to have proper evidence on which to advise pregnant women who may need to take medications for serious medical conditions. Beliefs in immaturity of the blood-brain barrier have held the field back for decades. Their history illustrates the importance of taking account of all the evidence and assessing its quality, rather than selecting papers that supports a preconceived notion or intuitive belief. This review attempts to right the wrongs. Based on careful translation of original papers, some published a century ago, as well as providing discussion of studies claiming to show barrier immaturity, we hope that readers will have evidence on which to base their own conclusions. [ABSTRACT FROM AUTHOR]

Shear distortion of amyloid-beta (Aβ) solutions accelerates amyloid cascade reactions that may yield different toxic oligomers than those formed in quiescent solutions. Recent experiments indicate that cerebrospinal fluid (CSF) and interstitial fluid (ISF) containing Aβ flow through narrow brain perivascular pathways and brain parenchyma. This paper suggests that such flow causes shear distortion of Aβ molecules involving conformation changes that may be one of the initiating events in the etiology of Alzheimer's disease. Aβ shearing can occur in or around brain arteries and arterioles and is suggested as the origin of cerebral amyloid angiopathy deposits in cerebrovascular walls. Comparatively low flow rates of ISF within the narrow extracellular spaces (ECS) of the brain parenchyma are suggested as a possible initiating factor in both the formation of neurotoxic Aβ42 oligomers and amyloid fibrils. Aβ42 in slow-flowing ISF can gain significant shear energy at or near the walls of tortuous brain ECS flow paths, promoting the formation of a shear-distorted, excited state hydrophobic Aβ42* conformation. This Aβ42* molecule could possibly be involved in one of two paths, one involving rapid adsorption to a brain membrane surface, ultimately forming neurotoxic oligomers on membranes, and the other ultimately forming plaque within the ECS flow pathways. Rising Aβ concentrations combined with shear at or near critical brain membranes are proposed as contributing factors to Alzheimer's disease neurotoxicity. These hypotheses may be applicable in other neurodegenerative diseases, including tauopathies and alpha-synucleinopathies, in which shear-distorted proteins also may form in the brain ECS. [ABSTRACT FROM AUTHOR]

Segmentation of cerebral blood vessels is of great importance in diagnostic and clinical applications, especially for embolization of cerebral aneurysms and arteriovenous malformations (AVMs). In order to perform embolization of the AVM, the structural and geometric information of blood vessels from 3D images is of utmost importance. For this reason, the in-depth segmentation of cerebral blood vessels is usually done as a fusion of different segmentation techniques, often requiring extensive user interaction. In this paper we introduce the idea of line-shaped profiling with an application to brain blood vessel and AVM segmentation, efficient both in terms of resolving details and in terms of computation time. Our method takes into account both local proximate and wider neighbourhood of the processed pixel, which makes it efficient for segmenting large blood vessel tree structures, as well as fine structures of the AVMs. Another advantage of our method is that it requires selection of only one parameter to perform segmentation, yielding very little user interaction. [ABSTRACT FROM AUTHOR]

Purpose Vessel enhancement algorithms are often used as a preprocessing step for vessel segmentation in medical images to improve the overall segmentation accuracy. Each algorithm uses different characteristics to enhance vessels, such that the most suitable algorithm may vary for different applications. This paper presents a comparative analysis of the accuracy gains in vessel segmentation generated by the use of nine vessel enhancement algorithms: Multiscale vesselness using the formulas described by Erdt (MSE), Frangi (MSF), and Sato (MSS), optimally oriented flux (OOF), ranking orientations responses path operator (RORPO), the regularized Perona-Malik approach (RPM), vessel enhanced diffusion (VED), hybrid diffusion with continuous switch (HDCS), and the white top hat algorithm (WTH). Methods The filters were evaluated and compared based on time-of-flight MRA datasets and corresponding manual segmentations from 5 healthy subjects and 10 patients with an arteriovenous malformation. Additionally, five synthetic angiographic datasets with corresponding ground truth segmentation were generated with three different noise levels (low, medium, and high) and also used for comparison. The parameters for each algorithm and subsequent segmentation were optimized using leave-one-out cross evaluation. The Dice coefficient, Matthews correlation coefficient, area under the ROC curve, number of connected components, and true positives were used for comparison. Results The results of this study suggest that vessel enhancement algorithms do not always lead to more accurate segmentation results compared to segmenting nonenhanced images directly. Multiscale vesselness algorithms, such as MSE, MSF, and MSS proved to be robust to noise, while diffusion-based filters, such as RPM, VED, and HDCS ranked in the top of the list in scenarios with medium or no noise. Filters that assume tubular-shapes, such as MSE, MSF, MSS, OOF, RORPO, and VED show a decrease in accuracy when considering patients with an AVM, because vessels may vary from its tubular-shape in this case. Conclusions Vessel enhancement algorithms can help to improve the accuracy of the segmentation of the vascular system. However, their contribution to accuracy has to be evaluated as it depends on the specific applications, and in some cases it can lead to a reduction of the overall accuracy. No specific filter was suitable for all tested scenarios. [ABSTRACT FROM AUTHOR]

This paper describes the results of intraoperational monitoring of hemodynamic parameters (velocity and pressure) in brain vessels, carried out within the framework of 50 neurosurgical operations using a Volcano ComboMap instrumental measuring system. It is established that the introduced parameter of specific load used during the neurosurgical operations is a significant parameter for the success of the operation. [ABSTRACT FROM AUTHOR]

In this paper, we investigated the brain-sinus junction and especially the bridging veins linking these two organs. Two types of optical microscopy were used: conventional optical microscopy and digital microscopy. We used thin histological sections prepared from a human brain, and stained with Masson's trichrome, hemalun and orcein. Finally we observed the path of the bridging vein inside the brain-skull interface. At smaller scales, wavy collagen fiber bundles were found and characterized inside the vein walls. Taking into account the orientations of the different sections with reference to frontal planes, we found that the bridging vein has a very complex geometry, which increases the difficulty to determine fiber orientations in its walls. Nevertheless, we found that collagen fiber bundles are mainly circumferentially oriented in the superior sagittal sinus walls. In this paper, we were able to characterize precisely the path of the bridging vein from the brain to the sinus, with different magnifications. [ABSTRACT FROM AUTHOR]

The connection between the nasal cavity and the CNS by the olfactory neurones has been investigated extensively during the last decades with regard to its feasibility to serve as a direct drug transport route to the CSF and brain. This drug transport route has gained much interest as it may circumvent the blood-brain barrier (BBB), which prevents some drugs from entering the brain. Approximately 100 published papers mainly reporting animal experiments were reviewed to evaluate whether the experimental design used and the results generated provided adequate pharmacokinetic information to assess whether the investigated drug was transported directly from the olfactory area to the CNS. In the analysis the large anatomical differences between the olfactory areas of animals and humans and the experimental conditions used were evaluated. The aim of this paper was to establish the actual evidence for the feasibility of this direct transport route in humans. Twelve papers presented a sound experimental design to study direct nose to CNS transport of drugs based on the authors' criteria. Of these, only two studies in rats were able to provide results that can be seen as an indication for direct transport from the nose to the CNS. No pharmacokinetic evidence could be found to support a claim that nasal administration of drugs in humans will result in an enhanced delivery to their target sites in the brain compared with intravenous administration of the same drug under similar dosage conditions. [ABSTRACT FROM AUTHOR]

Subdural hematomas are one of the frequent complications of head injuries. Such hematomas result from exceeding the border strength values of bridging veins. Subdural haemorrhages are life-threatening and are a frequent cause of considerable pathologies. Traffic participants and also soldiers who participate in armed conflicts are the most vulnerable to head injuries. Although hematomas have been studied for many years the mechanism of hematoma formation has not been fully clarified as yet. In the paper, the effort of brain tissue structures due to the propagation of shock wave was analyzed. Particular attention was paid to the deformation ability and changes in the energy of bridging veins. This research was concerned with changes in mechanical properties of these veins in the frontal, parietal and occipital regions of the brain. For the present research the authors have constructed finite element models of brain tissue fragments and conducted numerical studies taking into account the boundary conditions arising from violent overloads that result from combat operations. As a result of the numerical analysis conducted, critical values of strain and stress have been obtained. The analysis showed high diversity in the properties of the different regions of the brain tissue. The studies carried out by the authors rendered it possible to assess the effort of the tissue structures of veins in connection with mechanical parameters, including geometrical parameters, in particular in relation to the likelihood of hematoma formation. [ABSTRACT FROM AUTHOR]

Neurovascular diseases are among the leading causes of mortality and permanent disability due to stroke, aneurysm, and other cardiovascular complications. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Marfan syndrome are two neurovascular disorders that affect smooth muscle cells through accumulation of granule and osmiophilic materials and defective elastic fiber formations respectively. Moyamoya disease, hereditary hemorrhagic telangiectasia (HHT), microcephalic osteodysplastic primordial dwarfism type II (MOPD II), and Fabry's disease are disorders that affect the endothelium cells of blood vessels through occlusion or abnormal development. While much research has been done on mapping out mutations in these diseases, the exact mechanisms are still largely unknown. This paper briefly introduces the pathogenesis, genetics, clinical symptoms, and current methods of treatment of the diseases in the hope that it can help us better understand the mechanism of these diseases and work on ways to develop better diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Current neuroimaging techniques with high spatial resolution constrain participant motion so that many natural tasks cannot be carried out. The aim of this paper is to show how a time-locked correlation-analysis of cerebral blood flow velocity (CBFV) lateralisation data, obtained with functional TransCranial Doppler (fTCD) ultrasound, can be used to infer cerebral activation patterns across tasks. In a first experiment we demonstrate that the proposed analysis method results in data that are comparable with the standard Lateralisation Index (LI) for within-task comparisons of CBFV patterns, recorded during cued word generation (CWG) at two difficulty levels. In the main experiment we demonstrate that the proposed analysis method shows correlated bloodflow patterns for two different cognitive tasks that are known to draw on common brain areas, CWG and Music Synthesis. We show that CBFV patterns for Music and CWG are correlated only for participants with prior musical training. CBFV patterns for tasks that draw on distinct brain areas, the Tower of London and CWG, are not correlated. The proposed methodology extends conventional fTCD analysis by including temporal information in the analysis of cerebral blood-flow patterns to provide a robust, non-invasive method to infer whether common brain areas are used in different cognitive tasks. It complements conventional high resolution imaging techniques. [ABSTRACT FROM AUTHOR]

Isolated symptomatic occlusion of the anterior cerebral artery (ACA) is a rare condition and until date, only few cases regarding the revascularization of the ACA have been reported. This paper reports on successful attempt to revascularize the ACA using superficial temporal artery (STA) in patient with isolated symptomatic occlusion of the ACA. A 69-year-old man presented with several episodes of transient weakness involving left lower extremity. Cerebral angiography showed occlusion of the right ACA at the A2 segment. After medical treatment failure, the patient underwent STAACA bypass surgery. Subsequent to surgery, there was immediate disappearance of transient ischemic attack and follow-up angiography showed favorable revascularization of the ACA territory. Bypass surgery can be considered in the patients with symptomatic occlusion of the ACA, who have experienced failure in medical treatment. [ABSTRACT FROM AUTHOR]

Chronic imaging of cerebral blood flow (CBF) is an important tool for investigating vascular remodeling after injury such as stroke. Although techniques such as Laser Speckle Contrast Imaging (LSCI) have emerged as valuable tools for imaging CBF in acute experiments, their utility for chronic measurements or cross-animal comparisons has been limited. Recently, an extension to LSCI called Multi-Exposure Speckle Imaging (MESI) was introduced that increases the quantitative accuracy of CBF images. In this paper, we show that estimates of chronic blood flow are better with MESI than with traditional LSCI. We evaluate the accuracy of the MESI flow estimates using red blood cell (RBC) photographic tracking as an absolute flow calibration in mice over several days. The flow measures computed using the MESI and LSCI techniques were found to be on average 10% and 24% deviant (n=9 mice), respectively, compared with RBC velocity changes. We also map CBF dynamics after photo-thrombosis of selected cortical microvasculature. Correlations of flow dynamics with RBC tracking were closer with MESI (r=0.88) than with LSCI (r=0.65) up to 2 weeks from baseline. With the increased quantitative accuracy, MESI can provide a platform for studying the efficacy of stroke therapies aimed at flow restoration. [ABSTRACT FROM AUTHOR]

Despite an archive of over 73,000 research papers published in the last two decades on the subject of Alzheimer's disease (AD), little clinical progress has been made relative to how people get sporadic AD and what can be done to help them avoid it. This review spotlights strategic steps that could be a turning point in the dramatic lowering of Alzheimer prevalence. The main strategy includes application of four pillars of prevention: 1) early identification of AD vascular risk factors; 2) early detection of AD vascular risk factors; 3) early intervention of AD vascular risk factors based on evidence-based medical decisions; 4) patient follow-up to assess and modify interventions as needed. Tandem to these four pillars of prevention, a proactive lifestyle consisting of a healthy diet coupled to physical and mental activity should be applied as part of any therapeutic intervention. We are persuaded by mounting and compelling evidence that AD is a multifactorial disorder kindled by vascular risk factors that generate chronic brain hypoperfusion (CBH) during advanced aging. A pathobiological cascade of biochemical events in the presence of CBH that leads to oxidative stress and neurodegeneration appears to involve multiple biofactors including micronutrients, trace metals, lipids, and pro-oxidants, as reviewed in this special issue of BioFactors. Modulation of these biofactors may help prevent or control incipient AD. © 2012 International Union of Biochemistry and Molecular Biology, Inc. [ABSTRACT FROM AUTHOR]

Background: A potential new treatment in smoking cessation and relapse prevention is nicotine vaccination which is based on active immunization against the nicotine molecule. This immunization will elicit the immune system to produce nicotine-specific antibodies that sequester nicotine in the blood stream, after inhaling tobacco products. The resulting antibody-antigen is too large to cross the blood-brain barrier and is therefore postulated to attenuate the rewarding effect of nicotine by preventing the latter from reaching its receptors in the brain and causing the release of dopamine. The aim of this paper is to describe the design of a phase IIb, multi-center, double blind, randomized, placebo controlled trial to assess the efficacy of the nicotine vaccine NicVAX® co-administered with varenicline (Champix®) and intensive counseling as an aid in smoking cessation and relapse prevention. Methods/design: Two centers will include a total of 600 smokers who are motivated to quit smoking. At week--2 these smokers will be randomized, in a 1:1 ratio, to either 6 injections of NicVAX® or placebo, both co-administered with 12-weeks of varenicline treatment, starting at week 0. The target quit day will be set after 7 days of varenicline treatment at week 1. Smokers will be followed up for 54 weeks. The primary outcome is defined as biochemically validated prolonged smoking abstinence from week 9 to 52. Secondary outcomes include safety, immunogenicity, smoking abstinence from week 37 to 52, abstinence from week 9 to 24, abstinence in the subset of subjects with the highest antibody response, and lapse/relapse rate. Discussion: This is the first study to assess the efficacy of a nicotine conjugate vaccine in combination with an evidence-based smoking cessation pharmacotherapy (varenicline) to quit smoking. Although NicVAX® is primarily designed as an aid to smoking cessation, our study is designed to explore its potential to maintain abstinence and prevent relapse. The results of this trial will give a unique insight in the potential of nicotine vaccination for relapse prevention. Trial registration: ClinicalTrials.gov: (NCT00995033) [ABSTRACT FROM AUTHOR]

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In multiple sclerosis (MS), compromised blood-brain barrier (BBB) integrity contributes to inflammatory T cell migration into the central nervous system. Matrix metalloproteinase-9 (MMP-9) is associated with BBB disruption and subsequent T cell migration into the CNS. The aim of this paper was to evaluate the effects of omega-3 fatty acids on MMP-9 levels and T cell migration. Peripheral blood mononuclear cells (PBMC) from healthy controls were pretreated with two types of omega-3 fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Cell supernatants were used to determine MMP-9 protein and activity levels. Jurkat cells were pretreated with EPA and DHA and were added to fibronectin-coated transwells to measure T cell migration. EPA and DHA significantly decreased MMP-9 protein levels, MMP-9 activity, and significantly inhibited human T cell migration. The data suggest that omega-3 fatty acids may benefit patients with multiple sclerosis by modulating immune cell production of MMP-9. [ABSTRACT FROM AUTHOR]

utoregulation, an important feature of the cerebral circulation, is affected in many diseases. Since genetically modified mice are a fundamental tool in biomedical research, including neuro(bio)logy also in this specie measurements of cerebral autoregulation (CA) are mandatory. However, this requires anesthesia that unfortunately significantly impacts cerebral perfusion and consequently might distort CA measurements directly or by altering arterial pCO. The latter can be avoided by artificial ventilation but requires several control measurements of blood gases, each consuming at least 100 μl of blood or 5% of a mouse's blood volume. To avoid such diagnostic hemorrhage, we systematically analyzed the effect of different common anesthetic protocols used for rodents in spontaneously breathing mice on CA measured with Laser speckle perfusion imaging. Halothane, Isoflurane and Pentobarbital abrogated CA and Ketamin/Xylazine as well as Chloralose had a moderate reproducibility. In contrast, the rather rarely used anesthetic Ethomidate applied in low doses combined with local anesthetics had the best reproducibility. Although with this anesthesia the lower CA limit was lower than with Ketamin/Xylazine and Chloralose as reported in the handful of papers so far dealing with CA in mice, we suggest Ethomidate as the anesthetic of choice for CA measurements in spontaneously breathing mice. [ABSTRACT FROM AUTHOR]

This paper presents basic data on organophosphonate (OP) mechanisms of action, especially by toxicokinetic/toxicodynamic (TK/TD) process correlations. It is generally accepted that at least during onset of OP biological systems interaction, blood and tissue cholinesterase’s inhibition represents OP exposure marker and initiating mechanisms for toxicodynamic effects, characteristic for cholinergic crisis. OP penetrability of various biological barriers conditioning TK characteristics are determined by a series of physico-chemical properties. Non-cholinergic effects, direct interactions with cellular structures and subsequent effects (excitotoxicity) triggered by cholinergic crisis are also briefly presented. Opposed to these OP TK/TD characteristics, the authors analysed the pharmacokinetic/pharmacodynamic (PK/PD) characteristics and their correlations for oximes, as basic OP antidotes, besides atropine and anticonvulsants. Phosphorilated cholinesterasis reactivators are mono or bispyridinium derivatives with quaternary ammonium atoms, high water solubility, ionized at physiological pH, distribution in extra-cellular space, very low digestive absorption and blood-brain barrier (BBB) penetrability. OP nerve gas acute toxicity is correlated with anti-acetylcholinesterase (AChE) activity and partition coefficient. The toxicity rank seems to be determined by lipophilicity, besides their specific AChE inhibitory property. It has the effect that acute toxicity is the resultant of a TD process closely linked and dependent in vivo upon molecular descriptors determinant for the TK process. For cholinesterasis reactivators, molecular and PK characteristics limit their effects, especially to the peripheral level. The absent or much reduced BBB penetrability allowed some researchers to suggest that reactivators’ penetration and presence at central level are not necessary. The study of PK/PD correlations, molecular descriptors and biological membrane permeability of oximes can better define their antidotal effects mechanisms and, maybe, open a new perspective for field development. [ABSTRACT FROM AUTHOR]

The linearized filtering approach to the hemodynamic system is limited in capturing the inherent nonlinearities of physiological systems. The nonlinear estimation method therefore should be thought of as a natural way to access the nonlinear data assimilation problem. In this paper, we present a nonlinear filtering algorithm which is computationally expensive compared to the existing linearization filtering algorithms, for hemodynamic data assimilation, to address the deficiencies inherent to linearization. Simultaneous estimation of the physiological states and the system parameters have been demonstrated in a simulated and real data. The method provides more reasonable inference about the parameters of models for hemodynamic data assimilation. [ABSTRACT FROM AUTHOR]

This paper proposes a novel computational methodology for modelling the haemodynamic effects of endovascular coil embolization for cerebral aneurysms. We employ high-resolution 3-D angiographic data to reconstruct the intracranial geometry and we model the coiled part of the aneurysm as a porous medium, with porosity decreasing as coils are inserted. The actual dimensions of the coils employed are used to determine the characteristics of the porous medium. Simulation results for saccular aneurysms from the anterior communicating and middle cerebral arteries show that insertion of coils rapidly changes intraaneurysmal blood flow and causes reduction in mural pressure and blood velocity up to stagnation, providing favorable conditions for thrombus formation and obliteration of the aneurysm. [ABSTRACT FROM AUTHOR]

The entry of therapeutic compounds into the brain and spinal cord is normally restricted by barrier mechanisms in cerebral blood vessels (blood–brain barrier) and choroid plexuses (blood–CSF barrier). In the injured brain, ruptured cerebral blood vessels circumvent these barrier mechanisms by allowing blood contents to escape directly into the brain parenchyma. This process may contribute to the secondary damage that follows the initial primary injury. However, this localized compromise of barrier function in the injured brain may also provide a ‘window of opportunity’ through which drugs that do not normally cross the blood–brain barriers are able to do so. This paper describes a systematic study of barrier permeability in a mouse model of traumatic brain injury using both small and large inert molecules that can be visualized or quantified. The results show that soon after trauma, both large and small molecules are able to enter the brain in and around the injury site. Barrier restriction to large (protein-sized) molecules is restored by 4–5 h after injury. In contrast, smaller molecules (286–10 000 Da) are still able to enter the brain as long as 4 days postinjury. Thus the period of potential secondary damage from barrier disruption and the period during which therapeutic compounds have direct access to the injured brain may be longer than previously thought. [ABSTRACT FROM AUTHOR]

A mathematical model for the rupture of cerebral saccular aneurysms is developed through the analysis of three-dimensional stress distribution in the aneurysm wall. We assume in this paper that a saccular aneurysm resembles a thin spherical shell (a spherical membrane), and then develop a strain-energy function valid for finite strain to analyze three-dimensional stress distribution in the aneurysm wall. We find that rupture occurs when the ratio of the wall thickness to the radius of the aneurysm is 6.1 × 10-3. We also conclude from our analysis that rupture can occur when the ratio of thickness to radius of the parent aneurysm equals the ratio of thickness to radius of the daughter aneurysm. These findings may be helpful to the neurosurgeon for predicting the rupture potential in patients presenting with unruptured aneurysms. [ABSTRACT FROM AUTHOR]

In most tissues and organs, the lymphatic circulation is responsible for the removal of interstitial protein and fluid but the parenchyma of the brain and spinal cord is devoid of lymphatic vessels. On the other hand, the literature is filled with qualitative and quantitative evidence supporting a lymphatic function in cerebrospinal fluid (CSF) absorption. The experimental data seems to warrant a re-examination of CSF dynamics and consideration of a new conceptual foundation on which to base our understanding of disorders of the CSF system. The objective of this paper is to review the key studies pertaining to the role of the lymphatic system in CSF absorption. [ABSTRACT FROM AUTHOR]

The paper deals with modelling and simulation of a human brain arterial system using analogous electromagnetic systems, especially propagation characteristics of electric transmission lines. Cascade connection of analogous equivalent transmission line elements represents a vessel tree concerning both the electromagnetic parameters and the topology. Electromechanical analogy between physiological and electromagnetic values enables a description and following simulation of a cerebral haemodynamics by means of electric circuits analogous relations. The vascular dynamics modelling and simulation represents an important tool for the non-invasive computer-aided investigation of the brain arteries pathological deformations. The presented simulation results give the information about the blood dynamic characteristics also in the case of cerebral arterial stenoses or aneurysms under various stenosis degrees. The obtained results can provide helpful knowledge for the practical treatment of the basic brain arteries. [ABSTRACT FROM AUTHOR]

Recent studies have shown that drugs that are normally unable to cross the blood-brain barrier (BBB) following intravenous injection can be transported across this barrier by binding to poly(butyl cyanoacrylate) nanoparticles and coating with polysorbate 80. However, the mechanism of this transport so far was not known. In the present paper, the possible involvement of apolipoproteins in the transport of nanoparticle-bound drugs into the brain is investigated. Poly(butyl cyanoacrylate) nanoparticles loaded with the hexapeptide dalargin were coated with the apolipoproteins AII, B, CII, E, or J without or after precoating with polysorbate 80. In addition, loperamide-loaded nanoparticles were coated with apolipoprotein E alone or again after precoating with polysorbate 80. After intravenous injection to ICR mice the antinociceptive threshold was measured by the tail flick test. Furthermore, the antinociceptive threshold of polysorbate 80-coated dalargin-loaded nanoparticles was determined in ApoEtm1Unc and C57BL/6J mice. The results show that only dalargin or loperamide-loaded nanoparticles coated with polysorbate 80 and/or with apolipoprotein B or E were able to achieve an antinociceptive effect. This effect was significantly higher after polysorbate-precoating and apolipoprotein B or E-overcoating. With the apolipoprotein E-deficient ApoEtm1Unc mice the antinociceptive effect was considerably reduced in comparison to the C57BL/6J mice. These results suggest that apolipoproteins B and E are involved in the mediation of the transport of drugs bound to poly(butyl cyanoacrylate) nanoparticles across the BBB. Polysorbate 80-coated nanoparticles adsorb these apolipoproteins from the blood after injection and thus seem to mimic lipoprotein particles that could be taken up by the brain capillary endothelial cells via receptor-mediated endocytosis. Bound drugs then may be further transported into the brain by diffusion following release within the endothelial cells or, alternatively, by transcytosis. [ABSTRACT FROM AUTHOR]

Functional MRI using blood oxygenation level-dependent (BOLD) contrast indirectly probes neuronal activity via evoked cerebral blood volume (CBV) and oxygenation changes. Thus, its spatio-temporal characteristics are determined by vascular physiology and MRI parameters. In this paper, we focus on the spatial distribution and time course of the fMRI signal and their magnetic field strength dependence. Even though much is still unknown, the following consistent picture is emerging: a) For high spatial resolution imaging, fMRI contrast-to-noise increases supra-linearly with field strength. b) The location and spacing of penetrating arteries and ascending veins in the cortical tissue are not correlated to cortical columns, imposing limitations on achievable point-spread function (PSF) in fMRI. c) Baseline CBV distribution may vary over cortical layers biasing fMRI signal to layers with high CBV values. d) The largest CBV change is in the tissue microvasculature, less in surface arteries and even less in pial veins. e) Venous CBV changes are only relevant for longer stimuli, and oxygenation changes are largest in post-capillary blood vessels. f) The balloon effect (i.e. slow recovery of CBV to baseline) is located in the tissue, consistent with the fact that the post-stimulus undershoot has narrower spatial PSF than the positive BOLD response. g) The onset time following stimulation has been found to be shortest in middle/lower layers, both in optical imaging and high-resolution fMRI, but we argue and demonstrate with simulations that varying signal latencies can also be caused by vascular properties and, therefore, may potentially not be interpreted as neural latencies. With simulations, we illustrate the field strength dependency of fMRI signal transients, such as the adaptation during stimulation, initial dip and the post-stimulus undershoot. In sum, vascular structure and function impose limitations on the achievable PSF of fMRI and give rise to complex fMRI transients, which contain time-varying amount of excitatory and inhibitory neuronal information. Nevertheless, non-invasive fMRI at ultra-high magnetic fields not only provides high contrast-to-noise but also an unprecedented detailed view on cognitive processes in the human brain. [ABSTRACT FROM AUTHOR]

Certain aneurysms of the anterior circulation continue to offer a technical challenge for safe exposure and clipping. The purpose of this paper was to describe the cranio-orbital approach for surgical clipping of complex aneurysms and to evaluate prospectively the associated complications of this approach. Prospective audit of all patients undergoing cranio-orbital approach for aneurysm surgery from 1997 to 2004 by the senior author. Twenty-five patients, eight male and 17 female, median age of 52 years, range 28 – 73. All patients had a standard pterional approach supplemented by an orbital osteotomy. In the 7-year period 367 patients underwent treatment for their aneurysms (169 clipped and 198 coiled). Of the 169 patients who were operated on, 29 had a skull base approach, of which 25 were cranio-orbital. The aneurysm location was as follows: 16 middle cerebral artery (MCA), three carotid bifurcation, four anterior communicating artery (ACOMM), one ophthalmic and one basilar. There were no approach-related complications. The cranio-orbital craniotomy can be a useful adjunct in the surgical treatment of giant or complex aneurysms. It offers the following advantages over a standard pterional approach: reduces operative distance; allows easy splitting of the sylvian fissure; and provides a wide arc of exposure with multiple working corridors. [ABSTRACT FROM AUTHOR]

In 1948, Seymour S. Kety and Carl F. Schmidt published back-to-back papers in the JCI that are widely acknowledged as landmarks. Upon publication, the studies resolved a century-old debate, irrefutably demonstrating that cerebral blood flow is regionally regulated. The reported findings turned out to be so powerful in their implications that they provided the inspirational spark that illuminated a brand-new field: functional brain imaging. Thus these papers are landmarks of the rarest kind, not only ending a controversy, but also giving birth to one of the most exciting fields within modern day neuro science. [ABSTRACT FROM AUTHOR]

Purpose: Flat panel C-arm CT images acquired in the interventional suite provide valuable information regarding brain parenchyma, vasculature, and device status during the procedure. However, these images often suffer from severe streak artifacts due to the presence of metallic objects such as coils. These artifacts limit the capability to make diagnostic inferences and thus need to be reduced for better image interpretation. The main purpose of this paper is to systematically evaluate the accuracy of one such C-arm CT based metal artifact reduction (MAR) algorithm and to demonstrate its usage in both stent and flow diverter assisted coil embolization procedures. Methods: C-arm CT images routinely acquired in 24 patients during coil embolization procedure (stent-assisted (12) and flow-diverter assisted (12)) were included in this study in a retrospective fashion. These images were reconstructed without and with MAR algorithm on an offline workstation and compared using quantitative image analysis metrics. This analysis was carried out to assess the improvements in both brain parenchyma and device visibility with MAR algorithm. Further, ground truth reference images from phantom experiments and clinical data were used for accurate assessment. Results: Quantitative image analysis of brain parenchyma showed uniform distribution of grayscale values and reduced image noise after MAR correction. The line profile plot analysis of device profile in both phantom and clinical data demonstrated improved device visibility with MAR correction. Conclusions: MAR algorithm successfully reduced streak artifacts from coil embolization in all cases, thus allowing more accurate assessment of devices and adjacent brain parenchyma. [ABSTRACT FROM AUTHOR]

The vascular hypothesis of Alzheimer’s disease postulates that disruption of the brain microvasculature is important for the accumulation of amyloid beta and increased neuroinflammation. Liver X Receptor agonist, GW3965, has been demonstrated to successfully modulate neuroinflammation and lipid metabolism in murine models of AD. This is partially due to increased expression of ApoE levels and increased mobility of endothelial progenitor cells. This paper analyzes changes in the neurovascular unit and in astrocytes and microglia markers following oral administration of GW3965 in a very old triple transgenic AD mice (3xTg-AD mice). We found that astrogliosis, but not activation of microglia, decreased in very old (24 months) 3xTg-AD mice treated with GW965. In addition, GW3965 increased LRP1 levels in neuron-like cells and partially restored microvascular morphology by decreasing tortuosity and increasing length as shown by Lectin immunostaining. Interestingly, these changes were associated with decreased Aβ in blood vessels. In conclusion, short-term treatment of 3xTg-AD mice with GW3965 restored microvascular architecture which may be important in the cognitive improvement previously shown. [ABSTRACT FROM AUTHOR]

A new vascular structure segmentation method, which is based on a cylindrical flux-based higher order tensor (HOT), is presented. On a vessel structure, the HOT naturally models branching points, which create challenges for vessel segmentation algorithms. In a general linear HOT model embedded in 3D, one has to work with an even order tensor due to an enforced antipodal-symmetry on the unit sphere. However, in scenarios such as in a bifurcation, the antipodally-symmetric tensor embedded in 3D will not be useful. In order to overcome that limitation, we embed the tensor in 4D and obtain a structure that can model asymmetric junction scenarios. During construction of a higher order tensor (e.g. third or fourth order) in 4D, the orientation vectors lie on the unit 3-sphere, in contrast to the unit 2-sphere in 3D tensor modeling. This 4D tensor is exploited in a seed-based vessel segmentation algorithm, where the principal directions of the 4D HOT is obtained by decomposition, and used in a HOT tractography approach. We demonstrate quantitative validation of the proposed algorithm on both synthetic complex tubular structures as well as real cerebral vasculature in Magnetic Resonance Angiography (MRA) datasets and coronary arteries from Computed Tomography Angiography (CTA) volumes. [ABSTRACT FROM AUTHOR]

The regulatory interplay between laminar shear stress and proinflammatory cytokines during homeostatic maintenance of the brain microvascular endothelium is largely undefined. We hypothesized that laminar shear could counteract the injurious actions of proinflammatory cytokines on human brain microvascular endothelial cell (HBMvEC) barrier properties, in-part through suppression of cellular redox signaling. For these investigations, HBMvECs were exposed to either shear stress (8 dynes/cm2, 24 hours) or cytokines (tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6), 0 to 100 ng/mL, 6 or 18 hours). Human brain microvascular endothelial cell 'preshearing'±cytokine exposure was also performed. Either cytokine dose-dependently decreased expression and increased phosphorylation (pTyr/pThr) of interendothelial occludin, claudin-5, and vascular endothelial-cadherin; observations directly correlating to endothelial barrier reduction, and in precise contrast to effects seen with shear. We further observed that, relative to unsheared cells, HBMvECs presheared for 24 hours exhibited significantly reduced reactive oxygen species production and barrier permeabilization in response to either TNF-α or IL-6 treatment. Shear also downregulated NADPH oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) activation in HBMvECs, as manifested in the reduced expression and coassociation of gp91phox and p47phox. These findings lead us to conclude that physiologic shear can protect the brain microvascular endothelium from injurious cytokine effects on interendothelial junctions and barrier function by regulating the cellular redox state in-part through NADPH oxidase inhibition. [ABSTRACT FROM AUTHOR]

The primary angiitis of the central nervous system (PACNS) is an entity with a very low incidence and prevalence. It is not clear why the inflammatory process of this entity is limited to the cerebral vasculature without systemic manifestations. Its clinical manifestations are very heterogeneous and make clinical diagnosis difficult. In most cases, a brain biopsy is required. Only the clinical suspicion and the ability to recognize the possible clinical and imagenological patterns of presentation make an accurate diagnosis possible. The vast majority of the treatment recommendations are given by series of case reports. The following paper described the clinical, imagenological, and histopathological characteristics of three Colombian patients with PACNS.Thestrategic therapeutic used in shown. [ABSTRACT FROM AUTHOR]

Circle of Willis (CoW) plays a significant role in maintaining the blood supply for the brain. Specifically, when the stenosis occurs in the internal carotid artery (ICA), abnormal structures of CoW would decrease the compensatory capacity, leading to the local insufficiency of cerebral blood supply. The present paper built a series of lumped parameter models for CoW, and simulated the blood redistribution caused by the unilateral ICA stenosis with different severities in cerebral arteries in the normal and abnormal CoW respectively. The results showed that when unilateral ICA stenosis occurred, the collateral circulation was built through the anterior communicating artery and the ipsilateral posterior communicating artery, maintaining the flow in cerebral arteries. The absence of the two communicating arteries would cause an obvious decrease of flow in local cerebral arteries in the anterior circulation. In conclusion, the two arteries play a significant role in maintaining the balance of cerebral blood supply in the development of ICA stenosis. [ABSTRACT FROM AUTHOR]

The article focuses on the neural activity regulation of T cells in the blood-brain barrier of a mouse with multiple sclerosis, wherein a gateway in the blood vessel was formed that allows T cells to enter the central nervous system (CNS).

Abstract: The present paper reports on numerical simulations of blood flow and magnetic drug carrier distributions in a complex brain vascular system. The blood is represented as a non-Newtonian fluid by the generalised power law. The Lagrangian tracking of the double-layer spherical particles is performed to estimate particle deposition under influence of imposed magnetic field gradients across arterial walls. Two situations are considered: neutral (magnetic field off) and active control (magnetic field on) case. The double-layer spherical particles that mimic a real medical drug are characterised by two characteristic diameters - the outer one and the inner one of the magnetic core. A numerical mesh of the brain vascular system consisting of multi-branching arteries is generated from raw MRI scan images of a patient. The blood is supplied through four main inlet arteries and the entire vascular system includes more than 30 outlets, which are modelled by Murray’s law. The no-slip boundary condition is applied for velocity components along the smooth and rigid arterial walls. Numerical simulations revealed detailed insights into blood flow patterns, wall-shear-stress and local particle deposition efficiency along arterial walls. It is demonstrated that magnetically targeted drug delivery significantly increased the particle capturing efficiency in the pre-defined regions. This feature can be potentially useful for localised, non-invasive treatment of brain tumours. [Copyright &y& Elsevier]

Abstract: Three-dimensional analyses of the spatial arrangement, spatial orientation and preferential directions of systems of fibers are frequent tasks in many scientific fields, including the textile industry, plant biology and tissue modeling. In biology, systems of oriented and branching lines are often used to represent the three-dimensional directionality and topology of microscopic blood vessels supplying various organs. In our study, we present a novel p(χ 2) (chi-square) method for evaluating the anisotropy of line systems that involves comparing the observed length densities of lines with the discrete uniform distribution of an isotropic line system with the χ 2-test. Using this method in our open source software, we determined the rose of directions, preferential directions and level of anisotropy of linear systems representing the microscopic blood vessels in samples of various regions from human brains (cortex, subcortical gray matter and white matter). The novel method was compared with two other methods used for anisotropy quantification (ellipsoidal and fractional anisotropy). All three methods detected different levels of anisotropy of blood microvessels in human brain. The microvascular bed in the cortex was closer to an isotropic network, while the microvessels supplying the white matter appeared to be an anisotropic and direction-sensitive system. All three methods were able to determine the differences between various brain regions. The advantage of our p(χ 2) method is its high correlation with the number of preferential directions of the line system. However, the software, named esofspy, is able to calculate all three of the measures of anisotropy compared and documented in this paper, thus making the methods freely available to the scientific community. [Copyright &y& Elsevier]

Abstract: Methotrexate is a cytostatic drug applied in adjuvant chemotherapy and associated with cognitive impairment in part of the cancer patients. In this paper we studied in rats whether a reduction in blood supply to the brain or neuroinflammation are possible mediators of this cognitive dysfunctionality. Methotrexate reduced hippocampal blood vessel density 1 week and 3 weeks after treatment as measured immunohistochemically with an endothelial barrier antigen. Since reduced brain vascularization may relate to lowered central glucose metabolism [18F]FDG PET was performed. Methotrexate reduced tracer uptake in the hippocampal region 1 week after treatment, which was not seen 3 weeks after treatment. Neuroinflammatory processes were explored via a number of methods: a microglia immunohistochemical marker was applied to hippocampal sections, [11C]PK11195 PET was performed, and cytokine levels in plasma and homogenized hippocampal tissue were measured. Methotrexate activated microglia in the hippocampus 1 week and 3 weeks after treatment. PET analysis, however, did not show an increase in hippocampal tracer uptake and the multiplex analysis of various cytokines showed that hippocampal cytokine levels were not increased after methotrexate administration. Methotrexate did reduce plasma cytokine levels indicating a suppression of peripheral immune functioning. Methotrexate reduces hippocampal blood vessel density, indicative of a reduced brain glucose metabolism, which may contribute to the cognitive impairment following methotrexate administration. Although methotrexate activates microglia activation in the hippocampus, no effects were seen in [11C]PK11195 tracer uptake or hippocampal cytokine levels. This suggests that the microglial activation in this study is not a marker for neuroinflammation. [Copyright &y& Elsevier]

Abstract: Histological and magnetic resonance imaging studies have demonstrated that age-associated alterations of the human brain may be at least partially related to vascular alterations. Relatively little information has been published on vascular changes associated with healthy aging, however. The study presented in this paper examined vessels segmented from standardized, high-resolution, magnetic resonance angiograms (MRAs) of 100 healthy volunteers (50 males, 50 females), aged 18–74, without hypertension or other disease likely to affect the vasculature. The subject sample was divided into 5 age groups (n =20/group) with gender equally distributed per group. The anterior cerebral, both middle cerebral, and the posterior circulations were examined for vessel number, vessel radius, and vessel tortuosity. Males exhibited larger vessel radii regardless of age and across all anatomical regions. Both males and females displayed a lower number of MRA-discernible vessels with age, most marked in the posterior circulation. Age-associated tortuosity increases were relatively mild. Our multi-modal image database has been made publicly available for use by other investigators. [Copyright &y& Elsevier]

Background: As a continuation of the previous findings in human fetuses, accidental finding of an accessory vascular component in the posterior part of CAC of human adult cadavers inspired the authors to present and compare its posterior part configuration. Case presentation: Examination was carried out on brains of 48 human adult cadavers, routinely dissected at the Institute of Forensic Medicine. The aberrant vessel in the posterior part of four CACs was discovered. Vascular components of the posterior segment of CAC or of the whole CAC were described and photographed. A comparison between fetal and adult cases was also presented. Conclusions: Based on the fact that the age of the four presented cases ranged from 73 to 84 and based on the causes of their death, we concluded that the angioarchitecture of the posterior part of the CAC is a consequence of the embryonic or primitive arterial stabilization and interaction with normal adult vessels. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE: Hyperdense middle cerebral artery sign (HMCAS) on CT is a well known indication of thromboembolic arterial occlusion. Its disappearance after thrombolytic therapy is poorly described. Taking the rate of HMCAS disappearance as a surrogate for MCA recanalisation, its prognostic value after intravenous thrombolysis was examined. METHODS: 1905 stroke patients with HMCAS on admission CT scan in the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) were studied. On follow-up CT scans 22–36 h after thrombolysis, HMCAS disappeared in 831 cases, persisted in 788 and was uncertain in 122; follow-up CT was not done in 164 cases. RESULTS: Patients whose HMCAS disappeared were younger (median age 67 years vs 69 years for persistent; p = 0.03), with milder stroke (admission National Institute of Health Stroke Scale (NIHSS) score was 16 vs 17; p<0.005) and were less likely to have early infarct signs on admission CT (26% vs 33%; p<0.005). Patients with disappearing HMCAS were more likely to have early improvement in NIHSS score (median improvement 2 vs 0 at 2 h; 4 vs 1 at 24 h), be independent at 3 months (42% vs 19%), with fewer deaths (15% vs 30%) than those with persistent HMCAS. In multivariate analysis, HMCAS disappearance independently predicted functional independence and survival. Early NIHSS improvement independently predicted HMCAS disappearance. CONCLUSIONS: HMCAS disappeared after intravenous thrombolysis in about half of cases and these patients had twice as good outcomes compared with those with persistent HMCAS. The prognosis in patients with MCA occlusion that persists after intravenous thrombolysis is poor, which may indicate the need for an alternative treatment approach to this subgroup. [ABSTRACT FROM AUTHOR]

In this paper, a mathematical model for the description of cerebral hemodynamics is developed. This model is able to simulate the regulation mechanisms working on the small cerebral arteries and arterioles, and thus to adapt dynamically the blood flow in brain. Special interest is laid on the release of catecholamines and their effect on heart frequency, cardiac output and blood pressure. Therefore, this model is able to describe situations of severe head injuries in a very realistic way. [ABSTRACT FROM AUTHOR]

Summary: Little is known about the effects of ageing on cerebral autoregulation (CA). To examine the relationship between age and CA in adults, we conducted a prospective study using a non-invasive protocol without external stimuli. We studied 32 subjects, aged 23–68 years. They were assigned to a young group (28±5 years) and an old group (54±8 years). The groups were sex-matched. Transcranial Doppler ultrasonography (TCD) was used to record bilateral middle cerebral artery flow velocities (CBFV, cm/sec). Noninvasive beat-to-beat tonometric arterial blood pressure (ABP) measurement of the radial artery was used to record spontaneous blood pressure fluctuations. The Mx, an index of dynamic cerebral autoregulation (dCA), was calculated from a moving correlation between ABP and CBFV. We did not find a correlation between age and Mx. No statistically significant difference in the Mx between the groups (0.27±0.23, young, vs. 0.37±0.24, old) was demonstrated. Age does not affect dynamic cerebral autoregulation assessed by the Mx index in healthy adult subjects. This study supports findings from previous papers wherein CA was measured with protocols which require external stimuli. Further studies are needed to determine CA in subjects above 70 years of age. [Copyright &y& Elsevier]

This paper presents a method of regional cerebral blood flow (CBF) measurement using PET data and an input function not involving the absolute concentration value of radioactivity. The value of the input function and the output function can be obtained from clinical data by regression analysis. The input and output functions are transformed to their Fourier image functions by the Fourier transform. The transfer function of the differential equation of a compartment model is obtained from these image functions. The CBF can be estimated by transfer function regression analysis. The results of the proposed and conventional methods are compared. © 2005 Wiley Periodicals, Inc. Syst Comp Jpn, 36(4): 20–26, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.20160 [ABSTRACT FROM AUTHOR]

Stroke represents an infrequent adverse reaction associated with cervical spine manipulation therapy. Attempts to identify the patient at risk and the type of manipulation most likely to result in these complications of manipulation have not been successful. A retrospective review of 64 medical legal cases of stroke temporally associated with cervical spine manipulation was performed to evaluate characteristics of the treatment rendered and the presenting complaints in patients reporting these complications. These files included records from the practitioner who administered the manipulation therapy, post stroke testing and treatment records usually by a neurologist, and depositions of the patient and the practitioner of manipulation as well as expert and treating physicians. A retrospective review of the files was carried out by three (two in 11 cases) researchers using the same data abstraction instrument to independently assess each case. These independent reviews were followed by a consensus review in which all reviewers reached agreement on file content. Ninety two percent of cases presented with a history of head and/or neck pain and 16 (25 %) cases presented with sudden onset of new and unusual headache and neck pain often associated with other neurological symptoms that may represent a dissection in progress. The strokes occurred at any point during the course of treatment. Certain patients reporting onset of symptoms immediately after first treatment while in others the dissection occurred after multiple manipulations. There was no apparent dose-response relationship to these complications. These strokes were noted following any form of standard cervical manipulation technique including rotation, extension, lateral flexion and non-force and neutral position manipulations. The results of this study suggest that stroke, particularly vertebrobasilar dissection, should be considered a random and unpredictable complication of any neck movement including cervical manipulation. They may occur at any point in the course of treatment with virtually any method of cervical manipulation. The sudden onset of acute and unusual neck and/or head pain may represent a dissection in progress and be the reason a patient seeks manipulative therapy that then serves as the final insult to the vessel leading to ischemia. [ABSTRACT FROM AUTHOR]

Summary. Two cases with fusiform aneurysm in the posterior cerebral artery are presented: The first one is a large fusiform aneurysm of the P2 segment of posterior cerebral artery (PCA) in a 58 years old patient and the second a fusiform aneurysm of the P3 segment of PCA in a 43 years old patient. The aneurysms were successfully treated the first by proximal ligation and the second by trapping of the aneurysm. The patients had no additional neurological deficits postoperatively and they are in an good condition, in four years and one year follow up respectively. The operative approaches and the radiological investigation in relation to the micro-anatomy of the posterior cerebral artery, as well as the outcome in these cases are discussed. [ABSTRACT FROM AUTHOR]