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.

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.

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.

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.

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.

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.

Cell trafficking through the choroid plexus.

The choroid plexus is a multifunctional organ that sits at the interface between the blood and cerebrospinal fluid (CSF). It serves as a gateway for immune cell trafficking into the CSF and is in an excellent position to provide continuous immune surveillance by CD4 (+) T cells, macrophages and dendritic cells and to regulate immune cell trafficking in response to disease and trauma. However, little is known about the mechanisms that control trafficking through this structure. Three cell types within the choroid plexus, in particular, may play prominent roles in controlling the development of immune responses within the nervous system: the epithelial cells, which form the blood-CSF barrier, and resident macrophages and dendritic cells in the stromal matrix. Adhesion molecule and chemokine expression by the epithelial cells allows substantial control over the selection of cells that transmigrate. Macrophages and dendritic cells can present antigen within the choroid plexus and/or transmigrate into the cerebral ventricles to serve a variety of possible immune functions. Studies to better understand the diverse functions of these cells are likely to reveal new insights that foster the development of novel pharmacological and macrophage-based interventions for the control of CNS immune responses.

Posttraumatic invasion of monocytes across the blood-cerebrospinal fluid barrier.

The invasion of inflammatory cells occurring after ischemic or traumatic brain injury (TBI) has a detrimental effect on neuronal survival and functional recovery after injury. We have recently demonstrated that not only the blood-brain barrier, but also the blood-cerebrospinal fluid (CSF) barrier (BCSFB), has a role in posttraumatic recruitment of neutrophils. Here, we show that TBI results in a rapid increase in synthesis and release into the CSF of a major chemoattractant for monocytes, CCL2, by the choroid plexus epithelium, a site of the BCSFB. Using an in vitro model of the BCSFB, we also show that CCL2 is released across the apical and basolateral membranes of the choroidal epithelium, a pattern of chemokine secretion that promotes leukocyte migration across epithelial barriers. Immunohistochemical and electron microscopic analyses of choroidal tissue provide evidence for the movement of monocytes, sometimes in tandem with neutrophils, along the paracellular pathways between adjacent epithelial cells. These data further support the pathophysiological role of BCSFB in promoting the recruitment of inflammatory cells to the injured brain.

[Arteries and veins of the lateral ventricle]. / Vascularisation des ventricules latéraux.

Tumors of the frontal horn of the lateral ventricle (LV) are only supplied by the posteromedial choroidal artery. Tumors of the body of the LV are supplied by the same artery. Tumors of the atrium of the LV with anterior extension are supplied by both posteromedial choroidal and posterolateral arteries. Tumors of the atrium with inferior extension are supplied by both anterior choroidal artery and posterolateral choroidal arteries. Tumors of the inferior horn are only supplied by anterior choroidal artery. The tumoral venous drainage is organized with three main groups of veins: a medial group, a lateral group and a choroidal group.

Preoperative vincristine for an inoperable choroid plexus papilloma: a case discussion and review of the literature.

The authors report the case of a 14-month-old boy with a large right intraventricular choroid plexus papilloma (CPP) for which the first attempt at resection resulted in life-threatening intraoperative hemorrhage. The tumor was unsuitable for embolization, and neoadjuvant ifosfamide, carboplatin, etoposide (ICE) chemotherapy had no effect on tumor size. However, chemotherapy with vincristine, although not impacting on CT perfusion parameters, resulted in a significant decrease in tumor size, enabling complete resection with manageable blood loss. The mechanism underlying the effect of vincristine in this case is uncertain, but it is a treatment strategy that warrants further evaluation for the treatment of CPPs that are not amenable to embolization.

The distributional nexus of choroid plexus to cerebrospinal fluid, ependyma and brain: toxicologic/pathologic phenomena, periventricular destabilization, and lesion spread.

Bordering the ventricular cerebrospinal fluid (CSF) are epithelial cells of choroid plexus (CP), ependyma and circumventricular organs (CVOs) that contain homeostatic transporters for mediating secretion/reabsorption. The distributional pathway ("nexus") of CP-CSF-ependyma-brain furnishes peptides, hormones, and micronutrients to periventricular regions. In disease/toxicity, this nexus becomes a conduit for infectious and xenobiotic agents. The sleeping sickness trypanosome (a protozoan) disrupts CP and downstream CSF-brain. Piperamide is anti-trypanosomic but distorts CP epithelial ultrastructure by engendering hydropic vacuoles; this reflects phospholipidosis and altered lysosomal metabolism. CP swelling by vacuolation may occlude CSF flow. Toxic drug tools delineate injuries to choroidal compartments: cyclophosphamide (vasculature), methylcellulose (interstitium), and piperazine (epithelium). Structurally perturbed CP allows solutes to penetrate the ventricles. There, CSF-borne pathogens and xenobiotics may permeate the ependyma to harm neurogenic stem cell niches. Amoscanate, an anti-helmintic, potently injures rodent ependyma. Ependymal/brain regions near CP are vulnerable to CSF-borne toxicants; this proximity factor links regional barrier breakdown to nearby periventricular pathology. Diverse diseases (e.g., African sleeping sickness, multiple sclerosis) take early root in choroidal, circumventricular, or perivascular loci. Toxicokinetics informs on pathogen, anti-parasitic agent, and auto-antibody distribution along the CSF nexus. CVOs are susceptible to plasma-borne toxicants/pathogens. Countering the physico-chemical and pathogenic insults to the homeostasis-mediating ventricle-bordering cells sustains brain health and fluid balance.

Endoscopic treatment of distal choroidal artery aneurysm.

Distal choroidal artery aneurysms stemming from the lateral wall of the ventricles are rare and are mostly associated with moyamoya disease. The treatment of these aneurysms is difficult because of their deep location. The authors report the case of a 50-year-old woman followed for moyamoya disease presenting with 2 intraventricular hemorrhages. Cerebral angiography showed an aneurysm located on the left distal choroidal artery. Magnetic resonance imaging also demonstrated that the lesion protruded from the lateral wall of the trigone of the left lateral ventricle. Using MR imaging-guided stereotactic localization, the aneurysm was accurately reached endoscopically and successfully resected from the parent artery. The patient was discharged neurologically intact. To the best of the authors' knowledge, this is the first report of a successfully endoscopically treated distal anterior choroidal artery aneurysm. Endoscopic surgery may be added to the armamentarium of procedures used to treat intraventricular aneurysms.

VEGF/VEGFR-2 changes in frontal cortex, choroid plexus, and CSF after chronic obstructive hydrocephalus.

Chronic hydrocephalus (CH) is often associated with decreased cerebral blood flow (CBF) and oxygen levels. While the exact pathophysiology is not clear, vascular endothelial growth factor (VEGF) and its receptor-2 (VEGFR-2) may be involved. Because the choroid plexus (CP) is involved in cerebrospinal fluid (CSF) production and secretes numerous growth factors including VEGF, it is important to understand VEGF/VEGFR-2 levels in the CP-CSF circulatory system. Our results showed significant decreases in CBF and VEGFR-2 levels in frontal cortex (FC) in CH compared with SC; there were no significant changes in VEGF levels. CBF change in FC was positively correlated with VEGFR-2 levels (P=0.024). Immunohistochemistry (IHC) showed robust expression of VEGF/VEGFR-2 in CP. After CH induction, ventricular CSF volume and VEGF levels significantly increased. These results suggest that the decreased VEGFR-2 levels in FC may be contributed to decreased CBF and increased ventricular CSF-VEGF levels possibly reflected a hypoxic response and/or accumulation of VEGF from CP secretion after blockage of CSF outlet. Further investigation into CSF-VEGF levels in different sites may provide a better understanding of VEGF/VEGFR-2 modulation in the normal and hydrocephalic brain, and may represent a feasible approach to potential therapeutic options for hydrocephalus.

Choroid plexus metastasis from papillary thyroid carcinoma presenting with intraventricular hemorrhage: case report.

OBJECTIVE: Metastases to the choroid plexus from extracranial tumors are rare. Kidney, lung, and colon are the common primary origins of choroid plexus metastases. Choroid plexus metastases from thyroid carcinoma are very rare, with only 2 cases reported thus far. We report the third case of choroid plexus metastasis from thyroid carcinoma. CLINICAL PRESENTATION: A 75-year-old man presented with severe headache, nausea, and vomiting. He had a history of thyroid carcinoma, which had metastasized to the lymph nodes and lung. Computed tomography, magnetic resonance imaging, and magnetic resonance angiography revealed right intraventricular hemorrhage with mild hydrocephalus, without evidence of a bleeding source. The bleeding source was assumed to be the choroid plexus metastasis in the trigone of the right lateral ventricle (following second admission). INTERVENTION: Surgery was performed using a navigation-assisted system. The tumor was entirely removed, including some choroid plexus tissue. A ventriculoperitoneal shunt was also performed to treat the hydrocephalus. Histopathological examination revealed brain metastasis from papillary thyroid carcinoma. Postoperatively, the patient showed good recovery, with nausea and vomiting improved, and gait disturbance diminished. The patient was discharged from the hospital one month later. CONCLUSION: Choroid plexus metastasis from papillary thyroid carcinoma is very rare, and this is the first case of intraventricular hemorrhage reported.

Ruptured aneurysms of the choroidal branches of the posterior inferior cerebellar artery: a review of the literature and a case report.

Aneurysms of the choroidal branches of the posterior inferior cerebellar artery (PICA) are quite rare; only seven such cases have been reported thus far. In this study, we present a very rare case of a ruptured aneurysm of a choroidal branch of the PICA; the aneurysm was exposed by splitting the vermis and resected after proximal arterial ligation. We have also undertaken a thorough review of the literature on aneurysms in choroidal branches of the PICA, focusing on the clinical presentation, etiology, radiological findings, and surgical strategies. We found that the aneurysms in our patient and the aneurysms in seven published case reports were small, and frequently associated with vascular anomalies. Intraventricular hemorrhage (IVH) in the fourth ventricle was detected in all eight cases. The outcomes of surgical treatment were generally favorable, notwithstanding the high incidence of rebleeding after rupture of distal PICA aneurysms. The recognition of predominant fourth ventricular hemorrhage should raise the suspicion of the presence of an underlying aneurysm, and digital subtraction angiograms (DSAs) should be immediately obtained in order to detect small aneurysms of the choroidal branches of the PICA.

Functional characterization of mouse organic anion transporting peptide 1a4 in the uptake and efflux of drugs across the blood-brain barrier.

This study investigated the role of a multispecific organic anion transporter, Oatp1a4/Slco1a4, in drug transport across the blood-brain barrier. In vitro transport studies using human embryonic kidney 293 cells expressing mouse Oatp1a4 identified the following compounds as Oatp1a4 substrates: pitavastatin (K(m) = 8.3 microM), rosuvastatin (K(m) = 12 microM), pravastatin, taurocholate (K(m) = 40 microM), digoxin, ochratoxin A, and [d-penicillamine(2,5)]-enkephalin. Double immunohistochemical staining of Oatp1a4 with P-glycoprotein (P-gp) or glial fibrillary acidic protein demonstrated that Oatp1a4 signals colocalized with P-gp signals partly but not with glial fibrillary acidic protein, suggesting that Oatp1a4 is expressed in both the luminal and the abluminal membranes of mouse brain capillary endothelial cells. The brain-to-blood transport of pitavastatin, rosuvastatin, pravastatin, and taurocholate after microinjection into the cerebral cortex was significantly decreased in Oatp1a4(-/-) mice compared with that in wild-type mice. The blood-to-brain transport of pitavastatin, rosuvastatin, taurocholate, and ochratoxin A, determined by in situ brain perfusion, was significantly lower in Oatp1a4(-/-) mice than in wild-type mice, whereas transport of pravastatin and [D-penicillamine(2,5)]-enkephalin was unchanged. The blood-to-brain transport of digoxin was significantly lower in Oatp1a4(-/-) mice than in wild-type mice only when P-gp was inhibited by N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918). Taken together, these results show that Oatp1a4 can mediate the brain-to-blood and blood-to-brain transport of its substrate drugs across the blood-brain barrier. The brain-to-plasma ratio of taurocholate, pitavastatin, and rosuvastatin was close to the capillary volume in wild-type mice, and it was not affected by Oatp1a4 dysfunction. Whether Oatp1a4 can deliver drugs from the blood to the brain remains controversial.

Electron microscopic study of the porcine choroid plexus epithelium.

The choroid plexus (CP) is a highly vascularized organ in the brain ventricles which acts as the main producer of cerebrospinal fluid (CSF). A study of the surface ultrastructure of the porcine CP was performed using scanning and transmission electron microscopy. The vascular walls of the capillaries were fenestrated. Epiplexus cells of different morphology were abundant on top of the epithelial surface. Two types of epithelial cells were present, characterized by the presence or absence of microvilli. Some epithelial cells contained cilia while other cells had large secretory protrusions called blebs. In the choroid epithelium of the lateral ventricles, some cells with large depressions were present. Cells with peduncles, such as recently discovered in the buffalo, could not be recognized. The variability of the choroidal surface structures clearly indicates the active role of the CP in the formation and maintenance of the CSF and its components.

Subcellular localization of transporters along the rat blood-brain barrier and blood-cerebral-spinal fluid barrier by in vivo biotinylation.

Nutrient transporters and ABC efflux pumps at the blood-brain barrier are major determinants of drug penetration into the brain. Immunohistochemical analysis of transporter subcellular localization is challenging due to the close apposition of the luminal and abluminal microvessel plasma membranes. We employed in vivo perfusion of biotinylation reagent through rat brain microvessels to domain-specifically label proteins exposed on the microvessel luminal surface. Using this approach, we analyzed the luminal/abluminal localization of a number of blood-brain barrier transporters identified by quantitative PCR profiling as being highly expressed and enriched in rat brain endothelial cells compared with whole brain. We also examined the apical/basal-lateral distribution of transporters in the choroid plexus, a secondary site for transport of nutrients between the blood and CNS. We detected P-glycoprotein (Pgp) (Abcb1), ATP-binding cassette (Abc) g2, multidrug resistance protein (Mrp) 4 (Abcc4), glucose transporter 1 (Glut1) (Slc2a1), Lat1 (Slc7a5), and monocarboxylate transporter-1 (Mct1) (Slc16a1) on the luminal surface of rat cerebral microvessels by both immunofluorescence staining and Western blotting of in vivo biotinylated proteins. Mrp1 (Abcc1) appeared primarily abluminal by immunofluorescence staining, and was barely detectable in the biotinylated protein fraction. Organic anion transporter (Oat) 3 (Slc22a8), organic anion transporter polypeptide (Oatp) 2b1 (Slco2b1, Oatpb), and Mrp5 (Abcc5) were not detected on the luminal surface using either method, while Oatp1a4 (Slco1a4, Oatp2) appeared to partially localize to the microvessel lumen by immunofluorescence staining, but was not detected in the biotinylated protein fraction by Western blotting. Lat1, Mrp1 and Mrp4 were detected on the basal-lateral surface of lateral ventricle choroid plexus epithelial cells. Mrp5, Oct3 and Oatp2b1 (Oatpb) were detected in the ependymal cells lining the ventricle. We did not detect Pgp expression in choroid plexus by immunofluorescence staining. In vivo biotinylation provides a method for domain-specific labeling of luminal surface proteins within the capillaries of the blood-brain barrier, allowing for biochemical analysis of protein localization and facilitating optical discrimination of the luminal and abluminal endothelial surfaces.

[A case of aphasia with preserved repetition due to anterior choroidal artery territory infarction].

A 55-year-old right-handed male patient with atrial fibrillation was admitted to our hospital because of a sudden disturbance of consciousness and right hemiparesis. Neurological examinations revealed left conjugate deviation of the eyes, aphasia, right hemianopsia without macula sparing using a Goldmann perimeter, right hemianesthesia, and right hemiparesis. Magnetic resonance imaging showed low intensity areas (left posterior limb of internal capsule, left cerebral peduncle of middle brain, a part of left substantia nigra, left amygdala, ventral posterior lateral nucleus and ventral anterior nucleus of left thalamus, left lateral geniculate body, and left occipital lobe) in T1 weighted image, due to the infarct in the left anterior choroidal artery territory. Aphasia in this case was accompanied with non-fluent speech, good repetition, naming deficits, and perseveration. We suggest that aphasia with anterior choroidal artery syndrome cannot be classified using the conventional system, and emphasize the importance of accurate descriptions of the symptoms characteristic of aphasia with anterior choroidal artery.