Transvenous Onyx embolization of a subependymal deep arteriovenous malformation with a single drainage vein: technical note.

Cerebral arteriovenous malformations (AVMs) are uncommon. Treatment options include embolization, radiosurgery and surgery, separately or combined, the final goal being complete occlusion of the malformation. We describe the case of a symptomatic small subependymal AVM with a single deep drainage vein previously treated unsuccessfully by radiosurgery and transarterial embolization. The AVM was successfully embolized transvenously using Onyx, achieving complete occlusion in a single treatment session.

Infarction of the lateral posterior choroidal artery territory after manipulation of the choroid plexus at the atrium: causal association with subependymal artery injury.

OBJECT: The atrium of the lateral ventricle is often affected by tumors, and some patients with these tumors suffer neurological deficits, including hemiparesis after surgery. The authors of this study investigated the possible mechanisms causing the relatively high incidences of ischemic complications associated with surgery approaching the atrium of the lateral ventricle. METHODS: Clinical records and radiological images of 28 patients were retrospectively studied. These patients had their lateral ventricles opened at the atrium during the resection of gliomas as well as other nonbenign brain tumors, and were treated for gliomas at our tertiary referral center in the Tohoku district, Japan, between January 2008 and December 2010. RESULTS: Routine postoperative diffusion-weighted MR images obtained within 72 hours after surgery detected infarction in the periatrial/periventricular regions in 7 patients, presumably corresponding to the lateral posterior choroidal artery (LPChA) territory. Five of these 7 patients suffered neurological sequelae with varying severities. The choroid plexus at the atrium was coagulated to achieve hemostasis during the surgery in all of these patients. Detailed analysis of microangiograms revealed ventriculofugal arteries arising from the lateral ventricle. Damage of the subependymal artery that supplies the ventriculofugal arteries caused by coagulation of the choroid plexus at the atrium probably resulted in the infarction in these patients. CONCLUSIONS: Neurosurgeons must be aware of the possibility of LPChA territory infarction during surgery in the atrial or periatrial regions caused by subependymal artery obstruction after manipulating or coagulating the choroid plexus near the atrium.

A specialized microvascular domain in the mouse neural stem cell niche.

The microenvironment of the subependymal zone (SEZ) neural stem cell niche is necessary for regulating adult neurogenesis. In particular, signaling from the microvasculature is essential for adult neural stem cell maintenance, but microvascular structure and blood flow dynamics in the SEZ are not well understood. In this work, we show that the mouse SEZ constitutes a specialized microvascular domain defined by unique vessel architecture and reduced rates of blood flow. Additionally, we demonstrate that hypoxic conditions are detectable in the ependymal layer that lines the ventricle, and in a subpopulation of neurons throughout the SEZ and striatum. Together, these data highlight previously unidentified features of the SEZ neural stem cell niche, and further demonstrate the extent of microvascular specialization in the SEZ microenvironment.

Neural transmembrane protease and endothelial Gs protein activation in cell contact-dependent signaling between neural stem/progenitor cells and brain endothelial cells.

Vasculature is an important component of the neural stem cell niche in brain. It regulates neural stem/progenitor (NS/P) cell self-renewal, differentiation, and migration. In the neurogenic niches of adult brain, NS/P cells lie close to blood vessels, and proliferating NS/P cells frequently contact the vasculature. In the present study we showed that NS/P cells in co-culture with brain endothelial (bEND) cells activated endothelial G proteins and p38 mitogen-activated protein kinase (p38 MAPK) and stimulated cytokine/chemokine expression. These NS/P cell-induced endothelial responses took place during NS/P cell and bEND cell direct contact and were critically dependent on the expression of the type II transmembrane serine protease matriptase (MTP) by NS/P cells, because knocking down of MTP in NS/P cells impaired and re-expression of MTP restored their ability to induce endothelial cytokine/chemokine expression, p38 MAPK, or G protein activation. Cholera toxin blocked NS/P cell-induced endothelial responses, suggesting that the endothelial G protein activated by NS/P MTP is in the G(s) subfamily. The addition of p38 MAPK inhibitor impaired NS/P cell-induced endothelial cytokine/chemokine expression. The known G protein-coupled receptor substrate of MTP, protease-activated receptor 2, was not involved in this system. These results revealed a novel signaling pathway in neural stem cell vascular niches that is mediated by neural MTP and endothelial G(s) protein signaling at the cell-cell interface. This is the first report of direct cell-cell signaling between NS/P and bEND cells.

Development of the area postrema: an immunohistochemical study in the macaque.

The organization and chemical development of the area postrema (AP) in the macaque monkey was studied by immunohistochemistry imaged with conventional and confocal microscopy from day 40 of gestation to adulthood. The thin ependyma of the adult was found to develop from a thick continuous structure beginning in the second trimester. It was later invaded by tyrosine hydroxylase immunoreactive (TH+) and dopamine beta-hydroxylase immunoreactive (DBH+) cells and fibers, suggesting a possible route for release of neurotransmitter directly into ventricular cerebrospinal fluid. Other TH+ and/or DBH+ fibers were found in close approximation to blood vessels. Prominent vascularity of the parenchyma of AP was present late in the first trimester (fetal day (Fd)57 in the macaque) and increased further until birth. By contrast, the underlying solitary nucleus was hypervascular at Fd57, but its vascularity rapidly declined by late in the second trimester. TH+ neurons first appeared late in the first trimester, and DBH+ neurons appeared in the second trimester; these findings are consistent with the view that catecholaminergic cells in AP are the earliest members of the A2 noradrenergic group. Catecholaminergic cells or fibers in AP contained little labeling for synaptic vesicular proteins, suggesting that the release of neurotransmitter there may not involve a synaptic mechanism. Synapses were first observed in mid-second trimester, and most were associated with GABA+ fibers.

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.

Microanatomy of the subependymal arteries of the lateral ventricle.

BACKGROUND: Scarce information about the anatomy of the subependymal arteries (SEAs) is present in the scientific literature. METHODS: Twenty cerebral hemispheres with injected arteries were microdissected, and the magnetic resonance imaging scans of 100 patients with lacunar infarcts were examined. RESULTS: The SEAs were found to range in diameter from 40 to 490 microm (mean, 149 microm) and in number between 3 and 12 (average, 5.2). Of these, numbers from 1 to 3 originated from the anterior choroidal artery (AChA), between 1 and 10 from the lateral posterior choroidal artery (LPChA), 1 from the medial posterior choroidal artery (MPChA), and 1 from the internal carotid artery. The SEAs most often arose from the choroidal branches (90%) and less frequently from the thalamic (30%), caudate (35%), or thalamocaudate twigs (20%). The SEAs of the AChA supplied the walls of the temporal horn (100%), the occipital horn (85%), and the atrium (35%). Those of the LPChA perfused the walls of the occipital horn (15%), the atrium (65%), the body of the ventricle (100%), and partially the frontal horn. The SEAs of the MPChA partially nourished the body and the frontal horn (10%). The SEAs may also occasionally supply the caudate nucleus (20%) and the stria terminalis. The anastomoses involving the SEAs were absent. In spite of this, ischemia in the territory of a single SEA was noticed in only 1% of our patients. CONCLUSIONS: The SEAs are tiny vessels that supply the walls of the lateral ventricle, as well as the caudate nucleus and the stria terminalis occasionally. The obtained anatomic data can have important neurosurgical implications in intraventricular operations.

The effects of venous ischaemia on the subependymal and choroid plexus morphology in rat.

Morphological changes of ependyma, subependyma and choroids plexus regions were evaluated after experimental anastomotic venous occlusion in twenty male Sprague-Dawley rats. In this model, small burr holes were made over the anterior and posterior anastomotic veins and after precisely locating these vessels, bipolar coagulation and microscissors were used to perform permanent occlusion. Three days later, rats were sacrificed by perfusion and fixation and specimens were evaluated by histopathological techniques. Morphological changes of ependymal, subependymal and choroids plexus cells were evaluated in operated and intact hemispheres and revealed cell proliferation in the subventricular zone adjacent to the territory of venous occlusion in the operated hemisphere as well as midline shift, brain oedema, subcortical petechial haemorrhage, brain infarction and hemispheric swelling. In conclusion, following anterior (the vein of Throlard) and posterior (the vein of Labbé) anastomotic vein occlusion, cell proliferation can be seen in the choroids plexus, ependymal and subependymal regions in rats. We conclude that these morphological changes might be part of a self-repairing mechanism in the brain.

Anatomic analysis of blood vessels in germinal matrix, cerebral cortex, and white matter in developing infants.

The germinal matrix (GM) located in the thick subependymal cell layer of the thalamostriate groove is a major site of cerebral hemorrhage in premature infants. Comparing the morphology of vasculature among GM, gray and white matter of the brain may help in understanding the pathogenesis of GM hemorrhage and also of periventricular leukomalacia. The objective of the present study was to determine the morphology of blood vessels in the GM, gray matter, and white matter and to examine maturational changes in the morphology of these vessels as a function of gestational age. We measured vessel density, percentage of blood vessel area, mean surface area, length, breadth, perimeter, radius, and shape of blood vessels in coronal sections of the GM, gray matter, and white matter in postmortem human brain samples for 17 fetuses and premature infants of gestational age 16-40 wk and 2 adults. We performed immunohistochemical staining using anti-laminin primary antibody, confocal microscopy to acquire images, and analysis using Metamorph version 6.1. Vessel density and the percentage of blood vessel area increased as a function of gestational age in the GM, gray matter, and white matter (p < 0.001 each). The blood vessel density and the percentage of blood vessel area were largest in the GM followed by gray matter and then white matter in all of the gestational age categories (p < 0.001 for all comparisons). Increased vascularity of the GM compared with gray and white matter may play a role in GM hemorrhage, whereas a relatively low vascularity of white matter may increase the propensity for the occurrence of periventricular leukomalacia in premature infants

Subependymal veins in premature neonates: implications for hemorrhage.

The germinal matrix contains a concentrated network of blood vessels. The unusual structural qualities of these vessels are implicated as a factor underlying the high incidence of hemorrhage that occurs in the germinal matrix of prematurely born neonates. The present study is a histologic analysis of an postmortem examination series of brains collected from neonates born between 23 weeks gestation and term and is designed to determine if subependymal veins can be recognized in neonates born at the limits of viability, approximately 23 weeks gestation. Alkaline phosphatase histochemistry is used to differentiate cerebral afferent from efferent vessels. The results demonstrate that precursors of the subependymal veins can be recognized as early as the twenty-third gestational week. These veins increase progressively in diameter from 23 weeks to term, but the wall of the veins, which at early stages consists of endothelial cells only, does not thicken until after postconception week 36. Thus in all premature neonates, including the youngest capable of independent existence, the subependymal veins are present and appear vulnerable to rupture. These data support our suggestion that the structural immaturity of these veins in premature neonates is causally related to the high incidence of germinal matrix hemorrhage in these patients.

Venous variations in the region of the third ventricle: the role of MR venography.

In this study, we examined the anatomical variations of the subependymal veins in the region of the foramen of Monro and the third ventricle by MR time of flight (TOF) venography. Fifty healthy subjects, ten patients with third-ventricle tumors, and four patients with lateral-ventricle tumors were included in the study. The courses of the anterior septal vein (ASV), thalamostriate vein (TSV), and internal cerebral vein (ICV) were studied. The proximity of the venous angle, the false venous angle, and the ASV-ICV junction to the posterior margin of the foramen of Monro was measured. In 69 (53.9%) sides, the ASV-ICV junction was located at the venous angle and at the posterior margin of the foramen of Monro. In 59 (46.1%) sides, the ASV-ICV junction was located beyond the foramen of Monro. Our study shows the high incidence of posteriorly located ASV-ICV junctions, which can be crucial in the planning of a better surgical approach. We strongly recommend that MR venography, which is a short radiological examination, be used before one operates on third-ventricle and lateral-ventricle tumors.

Experience-associated structural events, subependymal cellular proliferative activity, and functional recovery after injury to the central nervous system.

Considerable structural plasticity is possible in the damaged neocortex and connected brain areas, and the potential for significant functional recovery remains even during the chronic phases of the recovery process. In this article, the authors review the literature on use-dependent morphologic events, focusing on the direct interaction of behavioral experience and structural changes associated with plasticity and degeneration. Experience-associated neural changes have the potential to either hinder or enhance functional recovery; therefore, issues concerning the nature, timing, and intensity of behavior-based intervention strategies are addressed.

Transthyretin Leu12Pro is associated with systemic, neuropathic and leptomeningeal amyloidosis.

We report a middle-aged woman with a novel transthyretin (TTR) variant, Leu12Pro. She had extensive amyloid deposition in the leptomeninges and liver as well as the involvement of the heart and peripheral nervous system which characterizes familial amyloid polyneuropathy caused by variant TTR. Clinical features attributed to her leptomeningeal amyloid included radiculopathy, central hypoventilation, recurrent subarachnoid haemorrhage, depression, seizures and periods of decreased consciousness. MRI showed a marked enhancement throughout her meninges and ependyma, and TTR amyloid deposition was confirmed by meningeal biopsy. The simultaneous presence of extensive visceral amyloid and clinically significant deposits affecting both the peripheral and central nervous system extends the spectrum of amyloid-related disease associated with TTR mutations. The unusual association of severe peripheral neuropathy with symptoms of leptomeningeal amyloid indicates that leptomeningeal amyloidosis should be considered part of the syndrome of TTR-related familial amyloid polyneuropathy.

Enzyme histochemical studies of membrane proteases in rat subfornical organ.

Localization of membrane proteases glutamyl aminopeptidase (EAP), microsomal alanyl aminopeptidase (mAAP), dipeptidyl peptidase IV (DPP IV) and gamma-glutamyl transpeptidase (gamma-GTP) were studied in vessels of the rat subfornical organ (SFO), ependyma which cover the surface of the SFO, and adjacent brain structures. Results of enzyme histochemical reactions showed strong activity for EAP, mAAP, and gamma-GTP, but absence of DPP IV in microvessels of SFO. The ependyma which cover the SFO was positive for gamma-GTP, but negative for other studied proteases. Our results showed that the spectrum of enzymes in the majority of the vessels of SFO is similar to that of the microvessels of the adjacent brain tissue which were positive for EAP, mAAP, and gamma-GTP, but negative for DPP IV. The relative intensity of the enzyme reactions in vessels varied from central to lateral locations in the SFO and the adjacent brain tissue. There was also a difference in the relative reaction intensity from one enzyme to the other. The presence and heterogeneous distribution of the enzymes are consistent with the hypothesis that membrane proteases of the microvascular endothelium constitute an enzyme-barrier between blood and parenchyma of the SFO and between blood and brain tissue, and may be involved in metabolism or modulation of various peptides when they contact the plasma membrane of the endothelial cells of the vessels.

Brain perfusion SPECT in a patient with a subtle venous angioma.

Brain SPECT of regional cerebral blood flow using I-123 IMP demonstrated a focally decreased perfusion area immediately adjacent to a venous angioma in a patient with simple partial seizures. A positive correlation was obtained among the location of the venous angioma, the decreased perfusion area on SPECT images, and the electroencephalographic focus. Anomalous venous drainage through a venous angioma may explain a perfusion disturbance in the surrounding brain of the angioma. High-resolution SPECT imaging with magnetic resonance guidance provides useful information on the pathophysiology of venous angiomas.

Posterior fossa venous angiomas with drainage through the brain stem.

PURPOSE: To describe 11 cases of posterior fossa venous angiomas with drainage through the brain stem. METHODS: Eleven cases of posterior fossa venous angioma with drainage through the brain stem were evaluated using MR. Correlation with known routes of venous drainage for the cerebellum and brain stem is made. RESULTS: Six of the 11 venous angiomas were found in the cerebellum, four in the brain stem; one involved both the cerebellum and brain stem. The cerebellar venous angiomas drained to subependymal veins about the fourth ventricle and dorsal pons. These then connected with an enlarged transmesencephalic or transpontine vein, to drain anteriorly to the anterior pontine veins. The brain stem angiomas had variable drainage depending on location. Evidence of hemorrhage was seen in five cases. CONCLUSION: Cerebellar and brain stem venous angiomas have several potential routes of drainage, including an enlarged vein traversing the pons, midbrain, or medulla. A knowledge of the normal venous anatomy of this region helps to understand the occurrence of these uncommon routes of venous drainage.

[Ultrastructure of the cerebrospinal fluid-brain barrier of the cerebral ventricles and blood-brain barrier of the vascular plexus in experimental aseptic leptomeningitis]. / Ul'trastruktura likvoroéntsefalicheskogo bar'era zheludochkov mozga i gematoéntsefalicheskogo bar'era sosudistykh spletenii pri éksperimental'nom asepticheskom leptomeningite.

The CSF-encephalic barrier of brain ventricles was examined at the submicroscopic level at different times of experimental aseptic leptomeningitis. In the acute period of the pathology, (3 to 7 days) the integrity of the bar was found to be disturbed because of acute inflammatory phenomena. In the subacute period (15 to 30 days), CSF hypertension was demonstrable. In the chronic period (90 days), the development of dystrophic and degenerative processes in the structures of the ependyma and vascular plexus were related to the disorders in CSF- and hemodynamics of the brain. Occlusion of the CSF tract was found to be associated with the impairment of the integrity of the blood- and CSF-encephalic barriers, marked edema end disintegration of the nerve tissue.

[Intraspinal organ in man]. / Intraspinal'nyi organ cheloveka.

In the ependymal zone of the spinal cord at the LI-SIII level an ependymal glandular organ has been described. Its highest secretory activity coincides with the period of the greatest functional activity of the human reproductive system functioning. Certain stages in development of the organ, its cell composition, blood supply, afferent and efferent innervation have been studied. In secretory cells of the organ peptide with cardio- and vasotonic properties has been identified immunochemically. The action of the organ is considered in connection with role, which the ependymal glands of the brain play in regulation of the organism's function.

Preservation of the ependyma of the mouse spinal cord by various vascular perfusion procedures.

Seventy-two mice were used to find out which of 13 vascular perfusion procedures gave best structural preservation of the spinal cord ependyma and central canal lumen. Best results were obtained by 3% glutaraldehyde in Tyrodes solution with 50% of normal NaCl amount, 0.06 M sucrose and 2% dextran T-40 (556 mOsmol, pH 7.2, 0-4 degrees C). This was perfused by a peristaltic pump at 40 ml/min for 10 min through a cannula inserted in the ascending aorta. No advantage was seen by heparin pretreatment or adding a prefixation rinse. With good tissue preservation the central canal was found to be round to oval in cross-sectional profile and almost free of intraluminal material.