Glial Layer Research Articles

Biomimetic design and integrated biofabrication of an in-vitro three-dimensional multi-scale multilayer cortical model

The lack of accurate and reliable in vitro brain models hinders the development of brain science and research on brain diseases. Owing to the complex structure of the brain tissue and its highly nonlinear characteristics, the construction of brain-like in vitro tissue models remains one of the most challenging research fields in the construction of living tissues. This study proposes a multi-scale design of a brain-like model with a biomimetic cortical structure, which includes the macroscopic structural features of six layers of different cellular components, as well as micrometer-scale continuous fiber structures running through all layers vertically. To achieve integrated biomanufacturing of such a complex multi-scale brain-like model, a multi-material composite printing/culturing integrated bioprinting platform was developed in-house by integrating cell-laden hydrogel ink direct writing printing and electrohydrodynamic fiber 3D printing technologies. Through integrated bioprinting, multi-scale models with different cellular components and fiber structural parameters were prepared to study the effects of macroscopic and microscopic structural features on the directionality of neural cells, as well as the interaction between glial cells and neurons within the tissue model in a three-dimensional manner. The results revealed that the manufactured in vitro biomimetic cortical model achieved morphological connections between the layers of neurons, reflecting the structure and cellular morphology of the natural cortex. Micrometer-scale (10 μm) cross-layer fibers effectively guided and controlled the extension length and direction of the neurites of surrounding neural cells but had no significant effect on the migration of neurons. In contrast, glial cells significantly promoted the migration of surrounding PC12 cells towards the glial layer but did not contribute to the extension of neurites. This study provides a basis for the design and manufacture of accurate brain-like models for the functionalization of neuronal tissues.

Clinical, Anatomical, and Histological Features of the Rhomboid Lip and Considerations for Surgery Using a Retrosigmoid Approach: A Retrospective Study

The rhomboid lip is a neural tissue encountered during cerebellopontine angle surgery, with differing shape and extent among individuals. This study aimed to investigate the variation of rhomboid lips during posterior fossa surgery. In this retrospective study, we examined posterior cranial fossa surgeries performed using a retrosigmoid approach. Rhomboid lips were classified according to thickness, extent, and appearance, with some subjected to histological analysis. T2-weighted magnetic resonance imaging (MRI) of rhomboid lips was conducted. Among 304 surgeries, rhomboid lips were observed in 75 patients who underwent schwannoma or meningioma resection, facial spasm-related neurovascular decompression, and other surgeries (37, 2, 32, and 4 patients, respectively). Rhomboid lips were categorized based on apparent thickness: thin membranous type, resembling an arachnoid membrane, and thick parenchymal type. Rhomboid lip extension was classified by position relative to the choroid plexus: non-extension, lateral extension, and jugular foramen (41, 22, and 12 patients, respectively). Veins were observed on the rhomboid lip surface in 37 cases. The rhomboid lip was visible in only one case (parenchymal jugular foramen type) on MRI. Histologically, the rhomboid lip comprised an ependymal cell layer, a glial layer, and connecting tissue. The glial layer thickness determined the rhomboid lip thickness, which was greater in the parenchymal type than in the membrane type. In 42 patients, the rhomboid lip was dissected, with no complications observed. Morphological classification of the rhomboid lip and understanding of its anatomical details contribute to safe surgical field development for neurosurgeons.

Ultrastructural analysis and 3D reconstruction of the frontal sensory-glandular complex and its neural projections in the platyhelminth Macrostomum lignano.

The marine microturbellarian Macrostomum lignano (Platyhelminthes, Rhabditophora) is an emerging laboratory model used by a growing community of researchers because it is easy to cultivate, has a fully sequenced genome, and offers multiple molecular tools for its study. M. lignano has a compartmentalized brain that receives sensory information from receptors integrated in the epidermis. Receptors of the head, as well as accompanying glands and specialized epidermal cells, form a compound sensory structure called the frontal glandular complex. In this study, we used semi-serial transmission electron microscopy (TEM) to document the types, ultrastructure, and three-dimensional architecture of the cells of the frontal glandular complex. We distinguish a ventral compartment formed by clusters of type 1 (multiciliated) sensory receptors from a central domain where type 2 (collar) sensory receptors predominate. Six different types of glands (rhammite glands, mucoid glands, glands with aster-like and perimaculate granula, vacuolated glands, and buckle glands) are closely associated with type 1 sensory receptors. Endings of a seventh type of gland (rhabdite gland) define a dorsal domain of the frontal glandular complex. A pair of ciliary photoreceptors is closely associated with the base of the frontal glandular complex. Bundles of dendrites, connecting the receptor endings with their cell bodies which are located in the brain, form the (frontal) peripheral nerves. Nerve fibers show a varicose structure, with thick segments alternating with thin segments, and are devoid of a glial layer. This distinguishes platyhelminths from larger and/or more complex invertebrates whose nerves are embedded in prominent glial sheaths.

Synchronization in the two time-scale multiplex network with symplectic interactions

Mounting experimental evidence suggests a significant role for glial cells, particularly astrocytes, in shaping neuronal activity in both cell cultures and the brain, driving interest in exploring multi-component network dynamics [1]. These systems are modeled at varying levels of physiological detail, ranging from the Hodgkin-Huxley and Ullah models for neurons and astrocytes, respectively, to simple integrate-and-fire models or phase oscillators. Multiplex networks are commonly used to model generic dynamical phenomena, with an emphasis on network connectivity effects rather than the complexity of an individual cell’s behavior. This model is particularly advantageous due to its use of a two-layer network structure [2]. This structure accurately describes neural connectivity through the long-range random coupling, while glial cells interact locally through the diffusion of mediatory molecules. Furthermore, the oscillatory timescales between neural and glial cells differ by at least one order of magnitude. In this context, the analysis of synchronization is a focal point as it is a crucial process that underpins information processing, decision making, and movement control in living neural systems [3]. Network topology is known to be essential, where all-to-all coupling and random Erdos–Renyi connectivity support the second-order phase transition to global phase coherence. In contrast, regular local coupling such as a 2D lattice only permits frequency and phase locking. Additionally, symplectic networks are capable of demonstrating a first-order phase transition, which is commonly referred to as “explosive” synchronization [4]. Recently, studies have shown that combining model neural (random) and glial (regular lattice) oscillatory layers can lead to a variety of outcomes [5]. Specifically, this combination was found to induce a second-order phase transition in the regular glial layer. In addition, synchronization in both layers may be preceded by desynchronization as the coupling between the layers becomes stronger. Here we investigate synchronization in the multiplex neural-glial network, where the neural layer is symplectic and contains triadic interactions. We demonstrate that symplectic coupling in the neural layer can induce the first order transition in the regular (glial) layer. Additionally, we show that such a transition can be induced by strengthening the glial and interlayer coupling, even if the symplectic neural layer alone is below the synchronization threshold. Desynchronization in the neuronal layer, resulting from the moderated coupling to the glial layer, never occurs abruptly.

Pulsatile cerebral paraarterial flow by peristalsis, pressure and directional resistance

BackgroundA glymphatic system has been proposed that comprises flow that enters along cerebral paraarterial channels between the artery wall and the surrounding glial layer, continues through the parenchyma, and then exits along similar paravenous channels. The mechanism driving flow through this system is unclear. The pulsatile (oscillatory plus mean) flow measured in the space surrounding the middle cerebral artery (MCA) suggests that peristalsis created by intravascular blood pressure pulses is a candidate for the paraarterial flow in the subarachnoid spaces. However, peristalsis is ineffective in driving significant mean flow when the amplitude of channel wall motion is small, as has been observed in the MCA artery wall. In this paper, peristalsis in combination with two additional mechanisms, a longitudinal pressure gradient and directional flow resistance, is evaluated to match the measured MCA paraarterial oscillatory and mean flows.MethodsTwo analytical models are used that simplify the paraarterial branched network to a long continuous channel with a traveling wave in order to maximize the potential effect of peristalsis on the mean flow. The two models have parallel-plate and annulus geometries, respectively, with and without an added longitudinal pressure gradient. The effect of directional flow resistors was also evaluated for the parallel-plate geometry.ResultsFor these models, the measured amplitude of arterial wall motion is too large to cause the small measured amplitude of oscillatory velocity, indicating that the outer wall must also move. At a combined motion matching the measured oscillatory velocity, peristalsis is incapable of driving enough mean flow. Directional flow resistance elements augment the mean flow, but not enough to provide a match. With a steady longitudinal pressure gradient, both oscillatory and mean flows can be matched to the measurements.ConclusionsThese results suggest that peristalsis drives the oscillatory flow in the subarachnoid paraarterial space, but is incapable of driving the mean flow. The effect of directional flow resistors is insufficient to produce a match, but a small longitudinal pressure gradient is capable of creating the mean flow. Additional experiments are needed to confirm whether the outer wall also moves, as well as to validate the pressure gradient.

Innexin-Mediated Adhesion between Glia Is Required for Axon Ensheathment in the Peripheral Nervous System.

Glia are essential to protecting and enabling nervous system function and a key glial function is the formation of the glial sheath around peripheral axons. Each peripheral nerve in the Drosophila larva is ensheathed by three glial layers, which structurally support and insulate the peripheral axons. How peripheral glia communicate with each other and between layers is not well established and we investigated the role of Innexins in mediating glial function in the Drosophila periphery. Of the eight Drosophila Innexins, we found two (Inx1 and Inx2) are important for peripheral glia development. In particular loss of Inx1 and Inx2 resulted in defects in the wrapping glia leading to disruption of the glia wrap. Of interest loss of Inx2 in the subperineurial glia also resulted in defects in the neighboring wrapping glia. Inx plaques were observed between the subperineurial glia and the wrapping glia suggesting that gap junctions link these two glial cell types. We found Inx2 is key to Ca2+ pulses in the peripheral subperineurial glia but not in the wrapping glia, and we found no evidence of gap junction communication between subperineurial and wrapping glia. Rather we have clear evidence that Inx2 plays an adhesive and channel-independent role between the subperineurial and wrapping glia to ensure the integrity of the glial wrap.SIGNIFICANCE STATEMENT Gap junctions are critical for glia communication and formation of myelin in myelinating glia. However, the role of gap junctions in non-myelinating glia is not well studied, yet non-myelinating glia are critical for peripheral nerve function. We found the Innexin gap junction proteins are present between different classes of peripheral glia in Drosophila. Here Innexins form junctions to facilitate adhesion between the different glia but do so in a channel-independent manner. Loss of adhesion leads to disruption of the glial wrap around axons and leads to fragmentation of the wrapping glia membranes. Our work points to an important role for gap junction proteins in mediating insulation by non-myelinating glia.

Experimental retina's dystrophy and the curcumin recovery effect on the evoked activity of visual system structures

The rehabilitative curcumin effect on visual system function was investigated in studies conducted on awake, unanesthetized rabbits. Analysis of the results obtained showed that after curcumin administration, certain changes in the evoked activity of the retina, superior colliculus, lateral geniculate body, and primary visual cortex were observed in the model of retinal dystrophy. The neuronal apparatus of the glial layer of the retina damaged in moderate retinal dystrophy led to functional disintegration of the mechanisms of electrogenesis. The curcumin administration led to an increase in the amplitude parameters of evoked potentials in all structures. The most pronounced curcumin effect was observed in the potentials of the visual cortex evoked by light stimuli, where certain changes in the configuration of evoked responses were noted.

Loss of nervous system complexity – Morphological analyses shed light on the neuronal evolution in Myzostomida (Annelida)

AbstractMyzostomida are putatively nested within the errant Annelida and exhibit a unique morphology. The latter fact might possibly be related to their long host‐dependent radiation. Hence, an incomplete segmentation, lack of prominent sensory structures in adults and a dorso‐ventrally flattened body are just some examples. Although numerous investigations of the nervous system exist for myzostomids, detailed ultrastructural as well as histological examinations of neuronal structures are lacking so far. Therefore, we investigate the nervous system of Myzostoma cirriferum Leuckart, 1836 using a comparative approach including paraffin histology, serial semi‐thin sections, immunohistochemistry and ultrastructural investigations. Our analyses reveal a lack of complexity within the anterior‐most neuronal condensation (herein called brain) of adult specimens. Hence, prominent tracts or glomeruli are absent, and a glial layer surrounding the brain or radial‐like glial cells are lacking. Nevertheless, the ultrastructure of the ventral nervous system is comparable to other Errantia. Therefore, our investigations hint towards a reduction of neuronal complexity in Myzostomida. Additionally, an ontogenetic simplification seems plausible, although further investigations are necessary to verify such a hypothesis. A simplification of neuronal structures due to a drastic change in lifestyle was so far mainly observed for basally branching annelid clades.

APOE Ɛ4 genotype is associated with thicker retinal layers in asymptomatic middle‐aged adults at high Alzheimer’s disease risk

AbstractBackgroundRetinal abnormalities have been demonstrated in patients with mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD), but findings in yet asymptomatic stages of the disease are scarce and inconsistent. This study examined the relationship of retinal thickness with APOE Ɛ4 genotype, the most important genetic risk factor for AD.MethodParticipants (n=245) were cognitively asymptomatic middle aged people taking part in the Israel Registry for Alzheimer's Prevention (IRAP) study, enriched for high AD‐risk due to parental history of the disease. Assessments included a complete ophthalmic examination, best‐corrected visual acuity (BCVA) evaluation and optic coherence tomography (SD‐OCT) imagingAPOE status was determined based on rs429358 and rs7412 SNPs' genotypes. MANCOVA was used to compare retinal thickness between APOE Ɛ4 carriers and non‐carriers adjusting for age, sex, education and BCVA in four retinal quadrants (nasal, inferior, temporal and superior).ResultParticipants' mean age was 59.60 (SD=6.42) years, 66.4% were women. Retinal thickness was significantly greater in APOE Ɛ4 carriers compared to non‐carriers (p=0.005), reaching statistical significance in the nasal (p=0.008) and inferior (p=0.022) regions. A secondary MANCOVA analysis examined differences between APOE4 carriers and non‐carriers in specific retinal layers‐ the neural and glial layers (Retinal Nerve Fiber Layer‐ RNFL, Ganglion Cell Layer– GCL, Inner Plexiform Layer‐IPL, Inner Nuclear Layer‐INL and the Outer Plexiform Layer‐OPL) and the non‐neural layers (Outer Nuclear Layer‐ONL and the Retinal Pigment Epithelium (RPE). In the nasal region, APOE4 carriers had thicker retinal nerve fiber layer (RNFL) (p=0.033), ganglion cell layer (GCL) (p=0.021) and inner plexiform layer (IPL) (p=0.010); in the inferior region, they had thicker GCL (p=0.035); and in the superior region, the APOE4 carriers had thicker IPL (p=0.019).ConclusionIn asymptomatic individuals enriched for AD risk, APOE4 carriers had thicker retinal nasal and inferior quadrants, which were driven primarily by the neural layers of the retina, but not by non‐neural layers. Our results suggest that retinal layers' thickness measurments may potentially be used as early biomarkers the disease.

Transitory and Vestigial Structures of the Developing Human Nervous System

As with many body organs, the human central nervous system contains many structures and cavities that may have had functions in embryonic and fetal life but are vestigial or atrophic at maturity. Examples are the septum pellucidum, remnants of the lamina terminalis, Cajal-Retzius neurons, induseum griseum, habenula, and accessory olfactory bulb. Other structures are transitory in fetal or early postnatal life, disappearing from the mature brain. Examples are the neural crest, subpial granular glial layer of Brun over cerebral cortex, radial glial cells, and subplate zone of cerebral cortex. At times persistent fetal structures that do not regress may cause neurological problems or indicate a pathologic condition, such as Blake pouch cyst. Transitory structures thus can become vestigial. Examples are an excessively wide cavum septi pellucidi, suprapineal recess of the third ventricle, trigeminal artery of the posterior fossa circulation, and hyaloid ocular artery. Arrested maturation might be considered another aspect of vestigial structure. An example is the persistent microcolumnar cortical architecture in focal cortical dysplasia type Ia, in cortical zones of chronic fetal ischemia, and in some metabolic/genetic congenital encephalopathies. Some transitory structures in human brain are normal adult structures in lower vertebrates. Recognition of transitory and vestigial structures by fetal or postnatal neuroimaging and neuropathologically enables better understanding of cerebral ontogenesis and avoids misinterpretations.

Peristaltic flow in the glymphatic system

The flow inside the perivascular space (PVS) is modeled using a first-principles approach in order to investigate how the cerebrospinal fluid (CSF) enters the brain through a permeable layer of glial cells. Lubrication theory is employed to deal with the flow in the thin annular gap of the perivascular space between an impermeable artery and the brain tissue. The artery has an imposed peristaltic deformation and the deformable brain tissue is modeled by means of an elastic Hooke’s law. The perivascular flow model is solved numerically, discovering that the peristaltic wave induces a steady streaming to/from the brain which strongly depends on the rigidity and the permeability of the brain tissue. A detailed quantification of the through flow across the glial boundary is obtained for a large parameter space of physiologically relevant conditions. The parameters include the elasticity and permeability of the brain, the curvature of the artery, its length and the amplitude of the peristaltic wave. A steady streaming component of the through flow due to the peristaltic wave is characterized by an in-depth physical analysis and the velocity across the glial layer is found to flow from and to the PVS, depending on the elasticity and permeability of the brain. The through CSF flow velocity is quantified to be of the order of micrometers per seconds.

The effect of axotomy on firing and ultrastructure of the crayfish mechanoreceptor neurons and satellite glial cells

Neurotrauma is among main causes of human disability and death. We studied effects of axotomy on ultrastructure and neuronal activity of a simple model object – an isolated crayfish stretch receptor that consists of single mechanoreceptor neurons (MRN) enwrapped by multilayer glial envelope. After isolation, MRN regularly fired until spontaneous activity cessation. Axotomy did not change significantly MRN spike amplitude and firing rate. However, the duration of neuron activity from MRN isolation to its spontaneous cessation decreased in axotomized MRN relative to intact neuron. [Ca2+] in MRN axon and soma increased 3–10 min after axotomy. Ca2+ entry through ion channels in the axolemma accelerated axotomy-stimulated firing cessation. MRN incubation with Ca2+ionophore ionomycin accelerated MRN inactivation, whereas Ca2+-channel blocker Cd2+ prolonged firing. Activity duration of either intact, or axotomized MRN did not change in the presence of ryanodine or dantrolene, inhibitors of ryanodin-sensitive Ca2+ channels in endoplasmic reticulum. Thapsigargin, inhibitor of endoplasmic reticulum Ca2+-ATPase, or its activator ochratoxin were ineffective. Ultrastructural study showed that the defect in the axon transected by thin scissors is sealed by fused axolemma, glial and collagen layers. Only the 30–50 μm long segment completely lost microtubules and contained swelled mitochondria. The microtubular bundle remained undamaged at 300 μm away from the axotomy site. However, mitochondria within the 200–300 μm segment were strongly condensed and lost matrix and cristae. Glial and collagen layers exhibited greater damage. Swelling and edema of glial layers, collagen disorganization and rupture occurred within this segment. Thus, axotomy stronger damages glia/collagen envelope, axonal microtubules and mitochondria.

Cytoarchitectural analysis of the neuron-to-glia association in the dorsal root ganglia of normal and diabetic mice.

Dorsal root ganglia (DRGs) host the somata of sensory neurons which convey information from the periphery to the central nervous system. These neurons have heterogeneous size and neurochemistry, and those of small-to-medium size, which play an important role in nociception, form two distinct subpopulations based on the presence (peptidergic) or absence (non-peptidergic) of transmitter neuropeptides. Few investigations have so far addressed the spatial relationship between neurochemically different subpopulations of DRG neurons and glia. We used a whole-mount mouse lumbar DRG preparation, confocal microscopy and computer-aided 3D analysis to unveil that IB4+ non-peptidergic neurons form small clusters of 4.7±0.26 cells, differently from CGRP+ peptidergic neurons that are, for the most, isolated (1.89±0.11 cells). Both subpopulations of neurons are ensheathed by a thin layer of satellite glial cells (SGCs) that can be observed after immunolabeling with the specific marker glutamine synthetase (GS). Notably, at the ultrastructural level we observed that this glial layer was discontinuous, as there were patches of direct contact between the membranes of two adjacent IB4+ neurons. To test whether this cytoarchitectonic organization was modified in the diabetic neuropathy, one of the most devastating sensory pathologies, mice were made diabetic by streptozotocin (STZ). In diabetic animals, cluster organization of the IB4+ non-peptidergic neurons was maintained, but the neuro-glial relationship was altered, as STZ treatment caused a statistically significant increase of GS staining around CGRP+ neurons but a reduction around IB4+ neurons. Ultrastructural analysis unveiled that SGC coverage was increased at the interface between IB4+ cluster-forming neurons in diabetic mice, with a 50% reduction in the points of direct contacts between cells. These observations demonstrate the existence of a structural plasticity of the DRG cytoarchitecture in response to STZ.

Glial ensheathment of the somatodendritic compartment regulates sensory neuron structure and activity

Sensory neurons perceive environmental cues and are important of organismal survival. Peripheral sensory neurons interact intimately with glial cells. While the function of axonal ensheathment by glia is well studied, less is known about the functional significance of glial interaction with the somatodendritic compartment of neurons. Herein, we show that three distinct glia cell types differentially wrap around the axonal and somatodendritic surface of the polymodal dendritic arborization (da) neuron of the Drosophila peripheral nervous system for detection of thermal, mechanical, and light stimuli. We find that glial cell-specific loss of the chromatin modifier gene dATRX in the subperineurial glial layer leads to selective elimination of somatodendritic glial ensheathment, thus allowing us to investigate the function of such ensheathment. We find that somatodendritic glial ensheathment regulates the morphology of the dendritic arbor, as well as the activity of the sensory neuron, in response to sensory stimuli. Additionally, glial ensheathment of the neuronal soma influences dendritic regeneration after injury.

Novel insights into the glia limitans of the olfactory nervous system.

Olfactory ensheathing cells (OECs) are often described as being present in both the peripheral and the central nervous systems (PNS and CNS). Furthermore, the olfactory nervous system glia limitans (the glial layer defining the PNS-CNS border) is considered unique as it consists of intermingling OECs and astrocytes. In contrast, the glia limitans of the rest of the nervous system consists solely of astrocytes which create a distinct barrier to Schwann cells (peripheral glia). The ability of OECs to interact with astrocytes is one reason why OECs are believed to be superior to Schwann cells for transplantation therapies to treat CNS injuries. We have used transgenic reporter mice in which glial cells express DsRed fluorescent protein to study the cellular constituents of the glia limitans. We found that the glia limitans layer of the olfactory nervous system is morphologically similar to elsewhere in the nervous system, with a similar low degree of intermingling between peripheral glia and astrocytes. We found that the astrocytic layer of the olfactory bulb is a distinct barrier to bacterial infection, suggesting that this layer constitutes the PNS-CNS immunological barrier. We also found that OECs interact with astrocytes in a similar fashion as Schwann cells in vitro. When cultured in three dimensions, however, there were subtle differences between OECs and Schwann cells in their interactions with astrocytes. We therefore suggest that glial fibrillary acidic protein-reactive astrocyte layer of the olfactory bulb constitutes the glia limitans of the olfactory nervous system and that OECs are primarily "PNS glia."

Area Postrema: Fetal Maturation, Tumors, Vomiting Center, Growth, Role in Neuromyelitis Optica

IntroductionThe area postrema in the caudal fourth ventricular floor is highly vascular without blood-brain or blood-cerebrospinal fluid barrier. In addition to its function as vomiting center, several others are part of the circumventricular organs for vasomotor/angiotensin II regulation, role in neuromyelitis optica related to aquaporin-4, and somatic growth and appetite regulation. Functions are immature at birth. The purpose was to demonstrate neuronal, synaptic, glial, or ependymal maturation in the area postrema of normal fetuses. We describe three area postrema tumors. MethodsSections of caudal fourth ventricle of 12 normal human fetal brains at autopsy aged six to 40 weeks and three infants aged three to 18 months were examined. Immunocytochemical neuronal and glial markers were applied to paraffin sections. Two infants with area postrema tumors and another with neurocutaneous melanocytosis and pernicious vomiting also studied. ResultsArea postrema neurons exhibited cytologic maturity and synaptic circuitry by 14 weeks'. Astrocytes coexpressed vimentin, glial fibrillary acidic protein, and S-100β protein. The ependyma is thin over area postrema, with fetal ependymocytic basal processes. A glial layer separates area postrema from medullary tegmentum. Melanocytes infiltrated area postrema in the toddler with pernicious vomiting; two children had primary area postrema pilocytic astrocytomas. ConclusionsAlthough area postrema is cytologically mature by 14 weeks, growth increases and functions mature during postnatal months. We recommend neuroimaging for patients with unexplained vomiting and that area postrema neuropathology includes synaptophysin and microtubule-associated protein-2 in patients with suspected dysfunction.

Intracranial glioependymal (neuroglial) cysts: a systematic review

Glioependymal cysts (GECs) are benign intracranial cysts that have been rarely reported in the literature. The exact pathogenesis of these developmental anomalies is controversial. Moreover, the terminology used to name GECs and other intracranial cysts is confusing because they are undistinguishably reported under a variety of names. The available information in the literature about GECs is scarce, and for this reason, a detailed description about these uncommon lesions is necessary. An illustrative case is presented; in addition, a PubMed and Scopus search adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed to include studies reporting patients with GECs. Different information was analyzed in these patients to describe the characteristics of this condition. In addition, different sources of literature were analyzed to complete the description of this clinical entity. The literature review yielded 26 cases of patients with intracranial GECs showing a diversity of clinical manifestations. All studies were case reports or small case series. Different characteristics of GECs are described. Moreover, the authors suggest an updated classification of intracranial benign cysts. The data collected from this review shows that GECs are rare and very often are erroneously named. They are congenital benign lesions with a neuroectodermal origin that share many radiological characteristics with a variety of intracranial benign cysts. The definite diagnosis of GECs is confirmed by the presence of a glial layer in the cyst wall at histological examination. The appropriate surgical technique should be selected according to the location of the cyst and its proximity to the ventricles or subarachnoid space.

A giant solid cystic inferior fourth ventricle subependymoma – Case report and literature review

Abstract Subependymomas are a rare subtype of ependymomas, slow growing WHO grade I tumors that develop either intracranial from the subependymal glial precursor cells layer of the ventricles or intramedullary. These tumors originate in the undifferentiated Subependymal layer of cells that can become either ependymocytes or astrocytes. Most of the subependymomas are located inside the fourth ventricle (50-60%). We reviewed the case of a 40 years old woman with a giant solid cystic fourth ventricle ependymoma. The patient underwent total resection of the tumor through a subociipital transvermian approach. We discussed the characteristics of these benign tumors and reviewed the literature on this subject and concluded that total resection is the treatment of choice for symptomatic Subependymomas localized in posterior fossa.

Abstract 141: G-Protein Coupled Receptors GPR37 and GPR37L1 Regulate Sodium Reabsorption in Renal Proximal Tubule Cells

GPR37 and GPR37L1 are closely related G-protein coupled receptors that are expressed mainly in brain glial cells and muscle-myenteric nerve layers in the GI tract. GPR37L1 transgenic mice have decreased systolic blood pressure (SBP) whereas GPR37L1 KO mice have increased SBP. However, there are no studies reporting kidney expression of GPR37 or GPR37L1 or their role in renal blood pressure regulation. Immunostaining and immunoblotting showed that GPR37 and GPR37L1 are expressed in the apical membrane of proximal tubules of the mouse kidney; RT-PCR on proximal tubule and collecting duct cells obtained by laser capture micro-dissection of mouse kidney sections, confirmed these findings. In addition, chronic high salt diet increased the renal expression of prosaposin, a precursor for saposin C, a natural ligand for GPR37 and GPR37L1. Infusion of prosaptide, a synthetic ligand for GPR37 and GPR37L1, decreased SBP in mice by 10 mm Hg. To determine the roles of GPR37 and GPR37L1 in renal Na+ transport, we over-expressed separately the two proteins in human renal proximal tubule (RPT) cells (n=3). Intracellular Na+ was increased in GPR37- or GPR37L1-transfected RPT cells (3.1 ± 0.8 and 3.2 ± 0.6 fold respectively, P<0.001) compared with mock-transfected cells. Immunoblot analyses showed increased phosphorylation of Erk1/2 (1.33 ± 0.03 and 1.52 ± 0.06 fold, P<0.05), and ribosomal S6 protein (1.29 ± 0.03.5 and 1.39 ± 0.08 fold, P<0.01) in RPT cells over-expressing GPR37 or GPR37L1, respectively. Na+,K+-ATPase expression was decreased by 29% ± 3.5 (P<0.05) in GPR37L1 transfected RPT cells, but was unaltered in GPR37 transfected RPT cells. Taken together, these results show that both GPR37 and GPR37L1 are expressed in RPT cells and signal via the Erk1/2 pathway. GPR37L1 increases intracellular Na+ in RPT cells by decreasing the exit of Na+ due to a decrease in Na+,K+-ATPase expression and activity at the basolateral membrane while GPR37 increases intracellular Na+, by a mechanism independent of Na+,K+-ATPase. These results indicate that GPR37 and GPR37L1 may play a role in Na+ reabsorption in RPT cells and may be novel targets to designing drugs to treat patients with hypertension.

Biopathology of astrocytes in human traumatic and complicated brain injuries. Review and hypothesis.

The biopathology of astrocyte cells in severe human brain traumatic injuries complicated with subdural and epidural haematoma and hygroma is reviewed. Clear and dense oedematous and hypertrophic reactive astrocytes are distinguished in severe primary traumatic vasogenic and secondary cytotoxic brain oedema. Swollen perineuronal astrocytes appear compressing and indenting clear and dark degenerated pyramidal and non-pyramidal nerve cells, degenerated myelinated axons and synaptic contacts. Hypertrophic astrocytes display dense cytoplasm and contain numerous rosettes of alpha, beta- and gamma-type glycogen granules, swollen mitochondria, dilated smooth and rough endoplasmic reticulum, oedematous Golgi apparatus, microtubules, gliofilaments, intermediate filaments, lysosomes and liposomes. The perisynaptic astrocyte ensheathment of synaptic contacts, containing beta type-glycogen granules, can be traced in the neuropil, surrounding swollen, bead-shaped dendritic profiles, and degenerated myelinated axons. This perisynaptic glial layer is absent in severe oedematous regions. The glycogen-rich and glycogendepleted perivascular astrocyte end-feet appear attached or dissociated from the capillary basement membrane. Phagocytic astrocytes can be seen engulfing degenerated synaptic contacts, necrotic membranes, degenerated myelinated axons, and myelin ovoids. Lipofuscin-rich astrocytes are also observed. The interastrocytary gap junctions appear either widened, fused or fragmented. The key role of aquaporin in astrocyte swelling and brain oedema is emphasized. The findings are compared with those reported in experimental traumatic animal models, a large variety of pathogenetically related neuropathological conditions, and in vivo and in vitro experimental conditions. The contribution of pathological astrocytes to neurobehavioral disorders, such as loss of consciousness, neurological deficits and seizures is emphasized. Some hypotheses are postulated related to the dissociated or absent perisynaptic layer, neurobiology of glycogen-rich and glycogen-depleted perivascular astrocytes, the glio-basal dissociation process, abnormal astrocyte-neuronal unit, and astrocyte participation in seizures in patients with severe and complicated brain injuries.