Unveiling the gut-brain axis: structural and functional analogies between the gut and the choroid plexus vascular and immune barriers.

The vasculature plays an essential role in the development and maintenance of blood-tissue interface homeostasis. Knowledge on the morphological and functional nature of the blood vessels in every single tissue is, however, very poor, but it is becoming clear that each organ is characterized by the presence of endothelial barriers with different properties fundamental for the maintenance of tissue resident immune homeostasis and for the recruitment of blood-trafficking immune cells. The tissue specificity of the vascular unit is dependent on the presence of differentiated endothelial cells that form continues, fenestrated, or sinusoidal vessels with different grades of permeability and different immune receptors, according to how that particular tissue needs to be protected. The gut-brain axis highlights the prominent role that the vasculature plays in allowing a direct and prompt exchange of molecules between the gut, across the gut vascular barrier (GVB), and the brain. Recently, we identified a new choroid plexus vascular barrier (PVB) which receives and integrates information coming from the gut and is fundamental in the modulation of the gut-brain axis. Several pathologies are linked to functional dysregulation of either the gut or the choroid plexus vascular barriers. In this review, we unveil the structural and functional analogies between the GVB and PVB, comparing their peculiar features and highlighting the functional role of pitcher and catcher of the gut-brain axis, including their role in the establishment of immune homeostasis and response upon systemic stimuli. We propose that when the gut vascular barrier-the main protecting system of the body from the external world-is compromised, the choroid plexus gatekeeper becomes a second barrier that protects the central nervous system from systemic inflammation.

Deconstructing the functional neuroanatomy of the choroid plexus: an ontogenetic perspective for studying neurodevelopmental and neuropsychiatric disorders.

The choroid plexus (CP) is a delicate and highly vascularized structure in the brain comprised of a dense network of fenestrated capillary loops that help in the synthesis, secretion and circulation of cerebrospinal fluid (CSF). This unique neuroanatomical structure is comprised of arachnoid villi stemming from frond-like surface projections-that protrude into the lumen of the four cerebral ventricles-providing a key source of nutrients to the brain parenchyma in addition to serving as a 'sink' for central nervous system metabolic waste. In fact, the functions of the CP are often described as being analogous to those of the liver and kidney. Beyond forming a barrier/interface between the blood and CSF compartments, the CP has been identified as a modulator of leukocyte trafficking, inflammation, cognition, circadian rhythm and the gut brain-axis. In recent years, advances in molecular biology techniques and neuroimaging along with the use of sophisticated animal models have played an integral role in shaping our understanding of how the CP-CSF system changes in relation to the maturation of neural circuits during critical periods of brain development. In this article we provide an ontogenetic perspective of the CP and review the experimental evidence implicating this structure in the pathophysiology of neurodevelopmental and neuropsychiatric disorders.

Identification of a choroid plexus vascular barrier closing during intestinal inflammation.

Up to 40% of patients with inflammatory bowel disease present with psychosocial disturbances. We previously identified a gut vascular barrier that controls the dissemination of bacteria from the intestine to the liver. Here, we describe a vascular barrier in the brain choroid plexus (PVB) that is modulated in response to intestinal inflammation through bacteria-derived lipopolysaccharide. The inflammatory response induces PVB closure after gut vascular barrier opening by the up-regulation of the wingless-type, catenin-beta 1 (Wnt/ß-catenin) signaling pathway, rendering it inaccessible to large molecules. In a model of genetically driven closure of choroid plexus endothelial cells, we observed a deficit in short-term memory and anxiety-like behavior, suggesting that PVB closure may correlate with mental deficits. Inflammatory bowel disease­related mental symptoms may thus be the consequence of a deregulated gut­brain vascular axis.

Impact of sex differences on thrombin-induced hydrocephalus and white matter injury: the role of neutrophils.

BACKGROUND: Thrombin has been implicated in playing a role in hydrocephalus development following intraventricular hemorrhage (IVH). However, the mechanisms underlying the sex differences to the detrimental effects of thrombin post-IVH remain elusive. METHOD: Three-month old male and female Sprague-Dawley rats underwent unilateral intracerebroventricular (ICV) injections of 3U or 5U thrombin, or saline, to examine differences in thrombin-induced hydrocephalus and white matter injury. Mortality, and lateral ventricle volume and white matter injury were measured on magnetic resonance imaging evaluation at 24 h post-injection. In addition, male rats were pretreated with 17-ß estradiol (E2, 5 mg/kg) or vehicle at 24 and 2 h prior to ICV injection of 3U thrombin. All rats were euthanized at 24 h post-injection for histology and immunohistochemistry. RESULTS: ICV injection of 5U thrombin caused 100 and 0% mortality in female and male rats, respectively. 3U of thrombin resulted in significant ventricular dilation and white matter damage at 24 h in both male and female rats, but both were worse in females (p < 0.05). Furthermore, neutrophil infiltration into choroid plexus and periventricular white matter was enhanced in female rats and may play a critical role in the sex difference in brain injury. Pre-treating male rats with E2, increased thrombin (3U)-induced hydrocephalus, periventricular white matter injury and neutrophil infiltration into the choroid plexus and white matter. CONCLUSIONS: ICV thrombin injection induced more severe ventricular dilation and white matter damage in female rats compared to males. Estrogen appears to contribute to this difference which may involve greater neutrophil infiltration in females. Understanding sex differences in thrombin-induced brain injury may shed light on future interventions for hemorrhagic stroke.

The anterior one third of the posterior limb of the internal capsule is also supplied by the anterior choroidal artery.

PURPOSE: It is universally recognized that the anterior choroidal artery (AChA) supplies the posterior two-third of the posterior limb of internal capsule (PLIC). On the other hand, the blood supply to the anterior one third of the PLIC has remained undetermined. We posit the anterior one third of the PLIC is also supplied by the AChA referring the previous microsurgical descriptions. METHODS: Ninety consecutive patients with isolated acute infarction in the PLIC were studied. We classified patients into 4 groups. 1. The anterior type that involved the anterior one-third part of the PLIC. 2. The posterior type that involved the caudal two-third part of the PLIC, 3. The combined type that located in the full length of the PLIC, 4. The dot type that restricted within PLIC up to10mm in diameter. RESULTS: Patient numbers in groups 1 through 4 were 7 (7.7%), 46 (51.1%), 9 (10.6%) and 28 (31.1%). The anterior type involved the medial part of pallidum (MPP) in 5 patients (71.4%) and none in the lateral thalamus (LT), while the posterior type involved MPP only in 6 patients (13.0%) and LT in 33 patients (71.7%). CONCLUSION: Corresponding to previous microsurgical descriptions, an occlusion of the proximal branches may cause anterior type infarct and that of the distal branches may cause posterior type infarcts. The anterior one third of the PLIC is also supplied by the branches of the AChA, albeit the low prevalence.

Intraoperative neuromonitoring during microsurgical clipping for unruptured anterior choroidal artery aneurysm.

OBJECTIVE: To investigate the safety and unexpected finding of the intraoperative neuromonitoring (IONM) including somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) during microsurgical clipping of an unruptured anterior choroidal artery (AChA) aneurysm. PATIENTS AND METHODS: From January 2011 to March 2018, the neurophysiological, clinical, and radiological data of 115 patients who underwent microsurgical clipping for an unruptured AChA aneurysm under IONM were retrospectively analyzed. The incidence of ischemic complications after microsurgical clipping of unruptured AChA aneurysms as well as the false-negative rate, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of IONM during surgery were calculated. RESULTS: Ischemic complications after the microsurgical clipping of an AChA aneurysm under IONM occurred in 7 of 115 patients (6.08%). Among them, 3 were symptomatic (2.6%). The false-negative rate of IONM for ischemic complications was 6.08% (7 patients). High specificity; 100% (95% confidence interval [95% CI] = 0.972-1.000), PPVs; 100% (95% CI = 0.055-1.000), and NPVs; 93% (95% CI = 0.945-0.973) with low sensitivity; 11.1% (95% CI = 0.006-0.111) were calculated. CONCLUSIONS: IONM including transcranial MEP during microsurgical clipping of unruptured AChA aneurysm might have limited usefulness. Therefore, other MEP monitoring using direct cortical stimulation or modified transcranial methodology should be considered to compensate for it.

Effect of choroidal collateral vessels on de novo hemorrhage in moyamoya disease: analysis of nonhemorrhagic hemispheres in the Japan Adult Moyamoya Trial.

OBJECTIVE: Following hemorrhagic stroke in moyamoya disease, de novo intracranial hemorrhage can occur in the previously unaffected nonhemorrhagic hemisphere. In the present analysis the authors intended to determine whether the presence in the nonhemorrhagic hemisphere of choroidal collateral vessels, which have been the focus of attention as a source of bleeding, affects the risk of de novo hemorrhage. METHODS: The subject of focus of the present cohort study was the nonhemorrhagic hemispheres of adult patients with hemorrhagic moyamoya disease enrolled in the Japan Adult Moyamoya Trial and allocated to the nonsurgical arm. The variable of interest was the presence of choroidal collaterals (also termed choroidal anastomoses), identified with baseline angiography and represented by a connection (anastomosis) between the anterior or posterior choroidal arteries and the medullary arteries. The outcome measure was de novo hemorrhage during the 5-year follow-up period, assessed in all nonhemorrhagic hemispheres. The incidence of de novo hemorrhage in the collateral-positive and -negative groups was compared. RESULTS: Choroidal collaterals were present in 15 of 36 (41.7%) nonhemorrhagic hemispheres analyzed. The overall annual risk of de novo hemorrhage was 2.0%. Three de novo hemorrhages occurred in the collateral-positive group, whereas no hemorrhage occurred in the collateral-negative group. The annual risk of de novo hemorrhage was significantly higher in the collateral-positive group than in the collateral-negative group (5.8% per year vs 0% per year; p = 0.017). All hemorrhage sites corresponded to the distribution of choroidal collaterals. CONCLUSIONS: The present preliminary results suggest that the presence of choroidal collaterals affects the risk of de novo hemorrhage in the nonhemorrhagic hemisphere, subject to verification in larger studies. Further studies are needed to determine the optimal treatment strategy for nonhemorrhagic hemispheres and asymptomatic patients.

Oxidative stress in the choroid plexus contributes to blood-cerebrospinal fluid barrier disruption during sepsis development.

BACKGROUND: The choroid plexus (CP), main component of blood-cerebrospinal fluid barrier (BCSFB), protects the brain from peripheral inflammation similar to the blood-brain barrier. Thus, CP is considered a critical target site of oxidative damage, which in sepsis oxidative stress is likely to be a major step in the development of brain damage. Functional alterations in CP may be associated with sepsis-induced brain injury. However, there is no description on the mechanisms associated with BCSFB disruption during sepsis development. MATERIALS AND METHODS: To test this hypothesis, we examined time-dependent oxidative stress markers in CP and permeability of BCSFB in rats submitted to polymicrobial sepsis by cecal ligation and puncture (CLP) or sham surgery (control). We assessed albumin cerebrospinal fluid/plasma concentration quotient (Qalb), an index of BCSFB dysfunction and in CP samples, the oxidative damage in lipids, proteins, antioxidant enzymes and nitrite/nitrate (N/N) concentration in 12, 24 and 48 h after CLP. RESULTS: The increase of BCSFB permeability is time-related to the increase of N/N concentration, oxidative damage to lipid and proteins, and decrease of antioxidant enzyme superoxide dismutase activity at 12 h in the CP; and decrease of catalase activity in 12 and 24 h. CONCLUSIONS: In experimental sepsis the BCSFB dysfunction occurs and oxidative stress seems to be a major step in this dysfunction.

Automated quantification of Haller's layer in choroid using swept-source optical coherence tomography.

OBJECTIVE: To develop an algorithm for automated quantification of Haller's layer in choroid using swept-source optical coherence tomography (OCT). BACKGROUND: So far, to understand the association of various diseases with structural changes of choroid, only gross indicators such as thickness, volume and vascularity index have been examined. However, certain diseases affect specific sublayers of the choroid. Accordingly, a need for targeted quantitation arises. In particular, there is significant interest in understanding Haller's layer, a choroidal sublayer comprising relatively large blood vessels. Unfortunately, its intricate vasculature makes, manual quantitation difficult, tedious, and error-prone. To surmount this difficulty, it is imperative to develop an algorithmic method. METHODOLOGY: The primary contribution of this work consists in developing an approach for detecting the boundary between Haller's and Sattler's layers, the latter comprising medium-sized vessels. The proposed algorithm estimates vessel cross-sections using exponentiation-based binarization, and labels a vessel large if its cross-section exceeds certain statistically determined threshold. Finally, the desired boundary is obtained as a smooth curve joining the innermost points of such large vessels. On 50 OCT B-scans (of 50 healthy eyes), our algorithm was validated both qualitatively and quantitatively, by comparing with intra-observer variability. Extensive statistical analysis was performed using metrics including Dice coefficient (DC), correlation coefficient (CC) and absolute difference (AD). RESULTS: The proposed algorithm achieved a mean DC of 89.48% (SD:5.03%) in close agreement with the intra-observer repeatability of 89.12% (SD:5.68%). Corresponding mean AD and mean CC were of 17.54 µm (SD:16.45µm) and 98.10% (SD:1.60%) which too approximate the respective intra-observer repeatability values 19.19 µm (SD:17.69 µm) and 98.58% (SD:1.12%). CONCLUSION: High correlation between algorithmic and manual delineations indicates suitability of our algorithm for clinically analyzing choroid in greater finer details, especially, in diseased eyes.

A new type of hyperplastic anterior choroidal artery.

Hyperplastic anomaly of the anterior choroidal artery (hyperplastic AchA) and posterior communicating artery of duplicate origin (duplicated Pcom) are rare vessel anomalies. With some literature review, we here report three cases of hyperplastic AchA, one of which was considered a new type of hyperplastic AchA. This case was not categorized into Takahashi classification.

Drug Clearance from Cerebrospinal Fluid Mediated by Organic Anion Transporters 1 (Slc22a6) and 3 (Slc22a8) at Arachnoid Membrane of Rats.

Although arachnoid mater epithelial cells form the blood-arachnoid barrier (BAB), acting as a blood-CSF interface, it has been generally considered that the BAB is impermeable to water-soluble substances and plays a largely passive role. Here, we aimed to clarify the function of transporters at the BAB in regulating CSF clearance of water-soluble organic anion drugs based on quantitative targeted absolute proteomics (QTAP) and in vivo analyses. Protein expression levels of 61 molecules, including 19 ATP-binding-cassette (ABC) transporters and 32 solute-carrier (SLC) transporters, were measured in plasma membrane fraction of rat leptomeninges using QTAP. Thirty-three proteins were detected; others were under the quantification limits. Expression levels of multidrug resistance protein 1 (Mdr1a/P-gp/Abcb1a) and breast cancer resistance protein (Bcrp/Abcg2) were 16.6 and 3.27 fmol/µg protein (51.9- and 9.82-fold greater than in choroid plexus, respectively). Among those organic anion transporters detected only at leptomeninges, not choroid plexus, organic anion transporter 1 (oat1/Slc22a6) showed the greatest expression (2.73 fmol/µg protein). On the other hand, the protein expression level of oat3 at leptomeninges was 6.65 fmol/µg protein, and the difference from choroid plexus was within two-fold. To investigate oat1's role, we injected para-aminohippuric acid (PAH) with or without oat1 inhibitors into cisterna magna (to minimize the contribution of choroid plexus function) of rats. A bulk flow marker, FITC-inulin, was not taken up from CSF up to 15 min, whereas uptake clearance of PAH was 26.5 µL/min. PAH uptake was completely blocked by 3 mM cephalothin (inhibits both oat1 and oat3), while 17% of PAH uptake was inhibited by 0.2 mM cephalothin (selectively inhibits oat3). These results indicate that oat1 and oat3 at the BAB provide a distinct clearance pathway of organic anion drugs from CSF independently of choroid plexus.

The diverse cellular responses of the choroid plexus during infection of the central nervous system.

The choroid plexus (CP) is responsible for the production of a large amount of the cerebrospinal fluid (CSF). As a highly vascularized structure, the CP also presents a significant frontier between the blood and the central nervous system (CNS). To seal this border, the epithelium of the CP forms the blood-CSF barrier, one of the most important barriers separating the CNS from the blood. During the course of infectious disease, cells of the CP can experience interactions with intruding pathogens, especially when the CP is used as gateway for entry into the CNS. In return, the CP answers to these encounters with diverse measures. Here, we will review the distinct responses of the CP during infection of the CNS, which include engaging of signal transduction pathways, the regulation of gene expression in the host cells, inflammatory cell response, alterations of the barrier, and, under certain circumstances, cell death. Many of these actions may contribute to stage an immunological response against the pathogen and subsequently help in the clearance of the infection.

Posterior Communicating Artery Giving Rise to Shared-Origin Anterior Choroidal Artery: Case Illustration.

BACKGROUND: The origin point of the anterior choroidal artery (AChA) is variable, typically arising from the supraclinoid internal carotid artery (ICA) distal to the posterior communicating artery (PComA) on either the posterolateral or posterior aspect of the ICA. Variations of AChA origin have important clinical implications, and rare origins reported previously include the ICA bifurcation and middle cerebral artery. We provide illustrations of a case of a shared-origin PComA and AChA. CASE DESCRIPTION: A young girl presented with intracranial hemorrhage and underwent angiography to evaluate for an underlying cause. Ultimately, 3-dimensional rotational angiography incidentally demonstrated a common origin of the AChA with the PComA. CONCLUSIONS: A rare case of a shared-origin AChA and PComA is reported for angiographic illustration. The radiologic findings, embryology behind the development of the AChA, and neurosurgical and neurovascular relevance of this variant are discussed. The importance of recognizing the origin of the AChA is emphasized.

Brain Arteriovenous Malformations Supplied by the Anterior Choroidal Artery: Treatment Outcomes and Risk Factors for Worsened Muscle Strength After Surgical Resection.

OBJECTIVE: The treatment of brain arteriovenous malformations (BAVMs) supplied by the anterior choroidal artery (AChA), or aBAVMs, remains challenging. The aim of this study was to determine the surgical outcomes and risk factors for worsened muscle strength (MS) after surgery in patients with aBAVMs. METHODS: We retrospectively reviewed 266 consecutive patients with BAVMs who underwent microsurgical resection of their BAVMs between September 2012 and June 2016. Patients were included if the BAVMs were entirely or partially supplied by the AChA. All patients had undergone preoperative diffusion tensor imaging, magnetic resonance imaging, 3-dimensional time-of-flight magnetic resonance angiography, and digital subtraction angiography followed by resection. Both functional and angioarchitectural factors were analyzed with respect to the change in MS. RESULTS: We identified 29 patients with aBAVMs who underwent surgical resection of the nidus. Radical resection was achieved in all patients. Thirteen (44.8%) patients suffered from postoperative short-term and 11 (37.9%) suffered from long-term MS deterioration. A shorter lesion-to-corticospinal tract distance (LCD) (P = 0.004) was significantly associated with postoperative short-term worsened MS. Shorter LCD (P = 0.018) and nidus supplied by cisternal segment of AChA (P = 0.026) were independent risk factors for the long-term MS worsening. The amplitudes and potential changes of intraoperative motor-evoked potential monitoring were consistent with the surgical outcomes. CONCLUSIONS: Surgical treatment of aBAVMs can cause a high incidence of MS deficits. Niduses supplied by cisternal segment of AChA and shorter LCD were crucial risk factors for postoperative MS worsening. Motor-evoked potential monitoring was an effective intraoperative technique to predict postoperative MS deficits.

Perfusion Deficits and Association with Clinical Outcome in Patients with Anterior Choroidal Artery Stroke.

BACKGROUND AND PURPOSE: Anterior choroidal artery (AChA) strokes have a varied pattern of tissue injury, prognosis, and clinical outcome. It is unclear whether perfusion deficit in AChA stroke is associated with the clinical outcome. This study aims to determine the frequency of perfusion abnormalities in AChA stroke and association with clinical outcome. METHODS: The study cohort was derived from ischemic stroke patients admitted to 2 stroke centers between July 2001 and July 2014. All patients received an acute magnetic resonance imaging (MRI) scan. Patients with ischemic stroke restricted to the AChA territory were included in the study. Lesion size was measured as the largest diameter on diffusion-weighted imaging (DWI) or apparent diffusion coefficient and divided into 2 groups (<20 mm or ≥20 mm). Group comparisons were performed among patients with and without perfusion abnormalities and based on diffusion diameter. Favorable clinical outcome was defined as discharge to home. RESULTS: A total of 120 patients were included in the study. Perfusion deficits were identified in 67% of patients. The admission National Institutes of Health Stroke Scale (NIHSS) was higher in patients with perfusion abnormalities (P = .027). Diameter lesion size on DWI was larger among patients with a perfusion deficit median [interquartile range], 1.63 [1.3-2.0], as compared with those without, 1.18 [1.0-1.7], P < .0001. Patients with a perfusion deficit were less likely to be discharged to home than those without (36% versus 60%, P = .013). CONCLUSIONS: Two thirds of patients with an AChA stroke have a perfusion deficit on MRI, higher admission NIHSS, and larger DWI lesion size at presentation.

Complement Component 3 Adapts the Cerebrospinal Fluid for Leptomeningeal Metastasis.

We molecularly dissected leptomeningeal metastasis, or spread of cancer to the cerebrospinal fluid (CSF), which is a frequent and fatal condition mediated by unknown mechanisms. We selected lung and breast cancer cell lines for the ability to infiltrate and grow in CSF, a remarkably acellular, mitogen-poor metastasis microenvironment. Complement component 3 (C3) was upregulated in four leptomeningeal metastatic models and proved necessary for cancer growth within the leptomeningeal space. In human disease, cancer cells within the CSF produced C3 in correlation with clinical course. C3 expression in primary tumors was predictive of leptomeningeal relapse. Mechanistically, we found that cancer-cell-derived C3 activates the C3a receptor in the choroid plexus epithelium to disrupt the blood-CSF barrier. This effect allows plasma components, including amphiregulin, and other mitogens to enter the CSF and promote cancer cell growth. Pharmacologic interference with C3 signaling proved therapeutically beneficial in suppressing leptomeningeal metastasis in these preclinical models.

Intraoperative Visualization of Subependymal Arteries at the Atrium Supplying the Descending Motor Pathway.

OBJECTIVE: We previously disclosed that damage to the subependymal arteries (SEAs) caused by coagulation of the choroid plexus at the atrium can result in infarction within the lateral posterior choroidal artery territory, followed by hemiparesis. The present study describes the intraoperative anatomical findings of the SEAs and choroid plexus at the atrium, which were verified only by a few cadaveric studies. METHODS: Locations of the SEA and descending motor pathway were determined with the neuronavigation system and subcortical electrical stimulation in 8 cases of periatrial brain tumor. Indocyanine green videoangiography was performed to verify the blood flow in the choroid plexus and SEAs. RESULTS: Intraoperative visualization of the SEAs was performed successfully in all patients. The neuronavigation system and subcortical electrical stimulation mapping demonstrated that these SEAs penetrated into the descending motor pathway. Indocyanine green depicted the blood flow of the SEAs entering the wall of the lateral ventricle and adjacent brain parenchyma. The blood flow directions between the SEAs and choroid plexus were not uniform, because the SEAs were filled ahead of the choroid plexus in 3 cases, whereas the choroid plexus was filled first in the other 2 cases. CONCLUSIONS: Manipulations to the inner side of the choroid plexus at the transition from the atrium to the body of lateral ventricle can damage the SEAs. Not only coagulation of the SEAs themselves, but also coagulation of choroid plexus itself may reduce the blood flow in the SEAs, resulting in ischemic complications at descending motor pathway.

Patency of the anterior choroidal artery covered with a flow-diverter stent.

OBJECT: The concept of the flow-diverter stent (FDS) is to induce aneurysmal thrombosis while preserving the patency of the parent vessel and any covered branches. In some circumstances, it is impossible to avoid dangerously covering small branches, such as the anterior choroidal artery (AChA), with the stent. In this paper, the authors describe the clinical and angiographic effects of covering the AChA with an FDS. METHODS: Between April 2011 and July 2013, 92 patients with intracranial aneurysms were treated with the use of FDSs in the authors' institution. For 20 consecutive patients (21.7%) retrospectively included in this study, this involved the unavoidable covering of the AChA with a single FDS during endovascular therapy. AChAs feeding the choroid plexus were classified as the long-course group (14 cases), and those not feeding the choroid plexus were classified as the short-course group (6 cases). Clinical symptoms and the angiographic aspect of the AChA were evaluated immediately after stent delivery and during follow-up. Neurological examinations were performed to rule out hemiparesis, hemihypesthesia, hemianopsia, and other cortical signs. RESULTS: FDS placement had no immediate effect on AChA blood flow. Data were obtained from 1-month clinical follow-up in all patients and from midterm angiographic follow-up in 17 patients (85.0%), with a mean length of 9.8 ± 5.4 months. No patient in either group complained of transient or permanent symptoms related to an AChA occlusion. In all cases, the AChA remained patent without any flow changes. CONCLUSIONS: The results of this study suggest that when impossible to avoid, the AChA may be safely covered with a single FDS during intracranial aneurysm treatment, irrespective of anatomy and anastomoses.

Cellular specificity of the blood-CSF barrier for albumin transfer across the choroid plexus epithelium.

To maintain the precise internal milieu of the mammalian central nervous system, well-controlled transfer of molecules from periphery into brain is required. Recently the soluble and cell-surface albumin-binding glycoprotein SPARC (secreted protein acidic and rich in cysteine) has been implicated in albumin transport into developing brain, however the exact mechanism remains unknown. We postulate that SPARC is a docking site for albumin, mediating its uptake and transfer by choroid plexus epithelial cells from blood into cerebrospinal fluid (CSF). We used in vivo physiological measurements of transfer of endogenous (mouse) and exogenous (human) albumins, in situ Proximity Ligation Assay (in situ PLA), and qRT-PCR experiments to examine the cellular mechanism mediating protein transfer across the blood-CSF interface. We report that at all developmental stages mouse albumin and SPARC gave positive signals with in situ PLAs in plasma, CSF and within individual plexus cells suggesting a possible molecular interaction. In contrast, in situ PLA experiments in brain sections from mice injected with human albumin showed positive signals for human albumin in the vascular compartment that were only rarely identifiable within choroid plexus cells and only at older ages. Concentrations of both endogenous mouse albumin and exogenous (intraperitoneally injected) human albumin were estimated in plasma and CSF and expressed as CSF/plasma concentration ratios. Human albumin was not transferred through the mouse blood-CSF barrier to the same extent as endogenous mouse albumin, confirming results from in situ PLA. During postnatal development Sparc gene expression was higher in early postnatal ages than in the adult and changed in response to altered levels of albumin in blood plasma in a differential and developmentally regulated manner. Here we propose a possible cellular route and mechanism by which albumin is transferred from blood into CSF across a sub-population of specialised choroid plexus epithelial cells.

A ruptured aneurysm located at a collateral artery that extended from the proximal A2 segment to the M1 segment, associated with an anomalous branch of the anterior choroidal artery and middle cerebral artery hypoplasia: case report.

We here describe the first case of a ruptured aneurysm located at a collateral artery that extended from the proximal A2 segment to the M1 segment, which was associated with an anomalous branch of the anterior choroidal artery and middle cerebral artery (MCA) hypoplasia. The aneurysm was revealed by angiograms and intraoperative findings. No previous accounts have been published of such an extremely rare vessel anomaly. In practice, this case highlights the urgent need to preoperatively recognize such vascular anomalies, as well as to better understand the collateral blood supply in cerebral ischemia associated with these MCA anomalies. Such knowledge will be helpful for planning optimal surgical procedures.