Neuraxis Research Articles

Food alert

The mere presence of lipids in the intestine is known to reduce nutrient intake in both rodents and humans by activating the intestinebrain neural axis. More recently, studies have indicated that the brain senses blood lipids directly to inhibit glucose production and maintain glucose homeostasis in rodents through a brainliver neural axis. Now comes the first demonstration that upper intestinal lipids rapidly inhibit glucose production through an intestinebrainliver neurocircuit. Work in rats shows that the lipids or fats which enter the small intestine trigger the afferent neuronal signal to the brain, which then sends signals to the liver to lower glucose production and blood glucose levels in as little as fifteen minutes. But eating a high-fat diet for just three days can interfere with this signal, disabling it so that it does not signal the other organs to lower blood glucose levels. This holds out the prospect that novel sites and targets may be revealed to lower glucose or blood sugar levels in those who are obese or have diabetes.

Upper intestinal lipids trigger a gut–brain–liver axis to regulate glucose production

Energy and glucose homeostasis are regulated by food intake and liver glucose production, respectively. The upper intestine has a critical role in nutrient digestion and absorption. However, studies indicate that upper intestinal lipids inhibit food intake as well in rodents and humans by the activation of an intestine-brain axis. In parallel, a brain-liver axis has recently been proposed to detect blood lipids to inhibit glucose production in rodents. Thus, we tested the hypothesis that upper intestinal lipids activate an intestine-brain-liver neural axis to regulate glucose homeostasis. Here we demonstrate that direct administration of lipids into the upper intestine increased upper intestinal long-chain fatty acyl-coenzyme A (LCFA-CoA) levels and suppressed glucose production. Co-infusion of the acyl-CoA synthase inhibitor triacsin C or the anaesthetic tetracaine with duodenal lipids abolished the inhibition of glucose production, indicating that upper intestinal LCFA-CoAs regulate glucose production in the preabsorptive state. Subdiaphragmatic vagotomy or gut vagal deafferentation interrupts the neural connection between the gut and the brain, and blocks the ability of upper intestinal lipids to inhibit glucose production. Direct administration of the N-methyl-d-aspartate ion channel blocker MK-801 into the fourth ventricle or the nucleus of the solitary tract where gut sensory fibres terminate abolished the upper-intestinal-lipid-induced inhibition of glucose production. Finally, hepatic vagotomy negated the inhibitory effects of upper intestinal lipids on glucose production. These findings indicate that upper intestinal lipids activate an intestine-brain-liver neural axis to inhibit glucose production, and thereby reveal a previously unappreciated pathway that regulates glucose homeostasis.

Bilateral malignant melanoma metastases to the internal auditory canal/cerebellopontine angle: surgical management and preservation of function

Although intracranial metastases of malignant melanomas are common, localization at the cerebellopontine angle (CPA) or in the internal auditory canal (IAC) is rare, and bilateral presentation especially so. We present the case of a 46-year-old Caucasian woman with bilateral IAC/CPA lesions and a prior history of malignant melanoma on the right leg. During preoperative investigations, the presence of the bilateral IAC/CPA lesions along with several radiologically identified lesions along the neural axis led to the suspicion that she had neurofibromatosis Type 2 despite her history of malignant melanoma and the lack of characteristic skin lesions and family history. Histopathological analysis of the resected lesion confirmed the intraoperative diagnosis of bilateral CPA malignant melanoma metastases. Surgical removal of the tumors via the retrosigmoid approach with preservation of normal bilateral facial nerve function and unilateral serviceable hearing, combined with control of the systemic disease, provided this patient with a near-normal quality of life for at least 42 months after the initial diagnosis of melanoma.

Atypical teratoid/rhabdoid tumour in sella turcica in an adult

Although atypical teratoid rhabdoid tumours preferentially arise in the posterior fossa of infants, we encountered a 56 year old woman with an atypical teratoid rhabdoid tumour located in the sella. She presented with right abducent and oculomotor nerve paresis. Magnetic resonance imaging demonstrated an intrasellar tumour impinging on the right cavernous sinus. Microscopically, the tumour was composed of cells with rhabdoid features; we observed atypia, eccentric nuclei, and intracytoplasmic inclusion bodies. The Ki-67 labeling index was around 30%. The tumour cells were positive for vimentin, epithelial membrane antigen, and neurofilament, but negative for INI1. Despite extended local brain and whole-spine irradiation she died of neural axis dissemination.

Epidermoid cysts associated with thoracic meningocele

Intraspinal tumours of cutaneous origin associated with various spinal dysraphisms have been well documented in the literature. However, the metachronous development of intra- and extra-medullary tumours in conjunction with dorsal meningocele is rare. The authors report a patient with a thoracic dorsal meningocele and congenital intradural extramedullary epidermoid tumour. The patient developed an intramedullary epidermoid growth 12 years later. Subtotal resection of the tumour predisposed to a later recurrence. Meningocele is not always an isolated clinical entity but the concurrent occult lesions are usually veiled by the more conspicuous surface anomaly. Thorough magnetic resonance imaging of the whole neural axis helps to identify associated pathologies. Delicate intradural exploration by a microsurgical approach is necessary to achieve appropriate treatment.

Hemangiopericitoma de la fosa posterior: a propósito de un caso

Hemangiopericytoma is an uncommon mesenchymal neoplasm arising from Zimmerman's pericytes, which usually locates in soft tissues. Meningeal hemangiopericytoma accounts for less than 1% of all intracranial tumours. Typically, it behaves aggressively, showing distinct tendency to recur locally or distantly along the neural axis and to present extraneural metastases. We describe a 74-year-old patient who presented unspecific symptoms and whose physical exam revealed a painless retroauricular mass which was adhered to skin. Neuroimaging studies showed a large posterior fossa tumour with intense enhancement after contrast infusion that caused striking occipital-mastoid osteolysis and which was exclusively fed by external carotid artery branches. The patient underwent gross total resection of the tumour, and once the histological diagnosis of hemangiopericytoma was confirmed, she underwent initial adjuvant radiotherapy. Sixteen months after surgery, the patient remains recurrence free. The treatment of choice of intracranial hemangiopericytoma is gross total resection, which must be attempted when technically feasible, followed by adjuvant radiotherapy providing total doses over 50 Gy. This combination has demonstrated increasing recurrence- free interval in these patients. Close and longterm follow-up is mandatory in order to achieve early diagnosis of recurrence or metastases in these patients, since they can appear several years, even decades, after initial proper treatment.

Columns of the Fornix, Not to Be Mistaken for the Cavum Septi Pellucidi on Prenatal Sonography

Visualization of the cavum septi pellucidi (CSP) is considered an integral part of the prenatal second-and third-trimester sonographic evaluations of the fetal neural axis. We have noted that another anatomic structure, the columns of the fornix, can be mistaken for the CSP and result in the missed diagnosis of agenesis of the corpus callosum. We describe a case in which the columns of the fornix were misinterpreted as representing the CSP during a sonographic evaluation at 18 weeks' gestation. After a follow-up sonogram at 35 weeks, agenesis of the corpus callosum was detected. A retrospective evaluation of the prevalence of forniceal columns was then performed in 100 consecutive sonograms of pregnancies between 18 and 24 weeks' gestation. A prospective study was then performed in 20 patients to determine the prevalence of visualization of the columns of the fornix. In 86 of 100 patients, the columns of the fornix were retrospectively identified as discrete and separate structures from the CSP. When additional views were obtained prospectively in the forebrain, the fornix could be identified in all 20 patients. The columns of the fornix may simulate the appearance of the CSP on second- and third-trimester sonograms. The distinction between these structures can be made because the columns of the fornix will show a linear reflection (3 lines) at their interface, whereas the CSP will appear as a fluid-filled triangular or rectangular fluid-filled space without a central line.

Auditory brainstem responses as a clinical evaluation tool in children after perinatal encephalopathy

Auditory brainstem responses (ABR) reveals the neurophysiological status of the neural axis. In this study we compared the ABR of healthy children, under 1-year-old, with children who suffered from perinatal encephalopathy (PE). The purpose of this study was to characterize the ABR differences between children with PE and healthy children in order to identify groups with specific neurophysiological profiles, associated with their neurological condition. Thirty-six children with perinatal encephalopathy (PE) and 36 healthy children, ages 1-12 months, were studied. The variables considered were: latencies of waves I, II, N1, III, V, and N2; interpeak latency interval (IPL) of waves I-III, III-V, and I-V; as well as amplitudes of waves I, III, and V. The results were analyzed using ANOVA, as well as Ji(2), and Ward's cluster analysis. The absolute latencies of the ABR showed an inverse correlation with the children's age. Latencies of waves I, II, N1, V, and N2, IPL III-V, and amplitude of waves III and V show significant differences (p<0.05) between healthy and PE children. Children with PE showed greater absolute latencies and larger wave amplitudes than the control group. Ward's cluster analysis, used to define the groups with similar functional characteristics, revealed three groups: fast, intermediate, and slow-responders, depending on their wave latencies and IPL wave amplitudes. These groups were gender- (p<0.03), age- (p<0.0001), and neurological damage- (p<0.01) related. Our data clearly show that the ABR obtained from PE children differ from ABR obtained from healthy children. PE infants showed larger wave latencies, intervals amplitudes than the control group. Three functional profiles resulted from the groups established using the Ward's method, and these indicate their neurological functional condition.

Ependymoma and intraparenchymal calcifying pseudoneoplasm of the neural axis: incidental collision or unique reactive phenomenon?

The so-called "calcifying pseudoneoplasm of the neural axis" is a rare tumefactive lesion presumed to be reactive in nature. To our knowledge, association with a true neoplasm has not been previously reported. We recently encountered the case of a 67-year-old woman who underwent resection of an incidentally discovered cerebellar cystic mass with a distinct, calcified component. Histology demonstrated a partially ossified, lobulated, chondrocalcific lesion surrounded by chronic inflammation, spindle to epithelioid cells, and occasional multinucleated giant cells-all features of calcifying pseudoneoplasm of the neural axis. A low-grade ependymoma associated with marked piloid gliosis was found contiguous to the lesion. The unique combination of an ependymoma with marked reactive gliosis and a calcifying pseudoneoplasm supports the reactive nature of the latter.

Otx1l, Otx2 and Irx1b establish and position the ZLI in the diencephalon

The thalamic complex is the major sensory relay station in the vertebrate brain and comprises three developmental subregions: the prethalamus, the thalamus and an intervening boundary region - the zona limitans intrathalamica (ZLI). Shh signalling from the ZLI confers regional identity of the flanking subregions of the ZLI, making it an important local signalling centre for regional differentiation of the diencephalon. However, our understanding of the mechanisms responsible for positioning the ZLI along the neural axis is poor. Here we show that, before ZLI formation, both Otx1l and Otx2 (collectively referred to as Otx1l/2) are expressed in spatially restricted domains. Formation of both the ZLI and the Irx1b-positive thalamus require Otx1l/2; embryos impaired in Otx1l/2 function fail to form these areas, and, instead, the adjacent pretectum and, to a lesser extent, the prethalamus expand into the mis-specified area. Conditional expression of Otx2 in these morphant embryos cell-autonomously rescues the formation of the ZLI at its correct location. Furthermore, absence of thalamic Irx1b expression, in the presence of normal Otx1l/2 function, leads to a substantial caudal broadening of the ZLI by transformation of thalamic precursors. We therefore propose that the ZLI is induced within the competence area established by Otx1l/2, and is posteriorly restricted by Irx1b.

West Nile Virus-Induced Neuroinflammation: Glial Infection and Capsid Protein-Mediated Neurovirulence

West Nile virus (WNV) infection causes neurological disease at all levels of the neural axis, accompanied by neuroinflammation and neuronal loss, although the underlying mechanisms remain uncertain. Given the substantial activation of neuroinflammatory pathways observed in WNV infection, we hypothesized that WNV-mediated neuroinflammation and cell death occurred through WNV infection of both glia and neurons, which was driven in part by WNV capsid protein expression. Analysis of autopsied neural tissues from humans with WNV encephalomyelitis (WNVE) revealed WNV infection of both neurons and glia. Upregulation of proinflammatory genes, CXCL10, interleukin-1beta, and indolamine-2',3'-deoxygenase with concurrent suppression of the protective astrocyte-specific endoplasmic reticulum stress sensor gene, OASIS (for old astrocyte specifically induced substance), was evident in WNVE patients compared to non-WNVE controls. These findings were supported by increased ex vivo expression of these proinflammatory genes in glia infected by WNV-NY99. WNV infection caused endoplasmic reticulum stress gene induction and apoptosis in neurons but did not affect glial viability. WNV-infected astrocytic cells secreted cytotoxic factors, which caused neuronal apoptosis. The expression of the WNV-NY99 capsid protein in neurons and glia by a Sindbis virus-derived vector (SINrep5-WNVc) caused neuronal death and the release of neurotoxic factors by infected astrocytes, coupled with proinflammatory gene induction and suppression of OASIS. Striatal implantation of SINrep5-WNV(C) induced neuroinflammation in rats, together with the induction of CXCL10 and diminished OASIS expression, compared to controls. Moreover, magnetic resonance neuroimaging showed edema and tissue injury in the vicinity of the SINrep5-WNVc implantation site compared to controls, which was complemented by neurobehavioral abnormalities in the SINrep5-WNVc-implanted animals. These studies underscore the important interactions between the WNV capsid protein and neuroinflammation in the pathogenesis of WNV-induced neurological disorders.

Choroid plexus carcinoma: a rare condition and its therapeutic management

Choroid plexus carcinomas are rare tumours, found chiefly during childhood. The commonest pattern of progression is via the neural axis. We present the case of a patient with unusual metastatic dissemination, affecting lungs and bones two years after diagnosis, and the approach adopted towards him.

Prenatal diagnosis of the rarely observed split notochord syndrome

Prenatal diagnosis of the rarely observed split notochord syndrome

Brain and sense organ anatomy and histology of two species of phyletically basal non‐Antarctic thornfishes of the Antarctic suborder Notothenioidei (Perciformes: Bovichtidae)

The predominantly non-Antarctic family Bovichtidae is phyletically basal within the perciform suborder Notothenioidei, the dominant component of the Antarctic fish fauna. In this article we focus on the South Atlantic bovichtids Bovichtus diacanthus, the klipfish from tide pools at Tristan da Cunha, and Cottoperca gobio, the frogmouth from the Patagonian shelf and Falkland Islands. We document the anatomy and histology of the brains, olfactory apparatus, retina, and cephalic lateral line system. We also use the microvascular casting agent Microfil to examine ocular vascular structures. We provide detailed drawings of the brains and cranial nerves of both species. Typical of perciforms, the brains of both species have a well-developed tectum and telencephalon and robust thalamic nuclei. The telencephalon of C. gobio is prominently lobed, with the dorsomedial nucleus more conspicuous than in any other notothenioid. The corpus cerebelli is relatively small and upright and, unlike other notothenioids, has prominent transverse sulci on the dorsal and caudal surfaces. Areas for lateral line mechanoreception (eminentia granularis and crista cerebellaris) are also conspicuous but olfactory, gustatory, and somatosensory areas are less prominent. The anterior lateral line nerve complex is larger than the posterior lateral line nerve in B. diacanthus, and in their cephalic lateral line systems both species possess branched membranous tubules (which do not contain neuromasts) with small pores. These are especially complex in B. diacanthus where they become increasingly branched and more highly pored in progressively larger specimens. Superficial neuromasts are sparse. Both species have duplex (cone and rod) retinae that are 1.25-fold thicker and have nearly 5-fold more photoreceptors and than those of most Antarctic notothenioids. Convergence ratios are also high for bovichtids. Bovichtus diacanthus has a yellow intraocular filter in the dorsal aspect of the cornea. Both species are unique among notothenioids in possessing all three vascular structures present in the generalized teleostean eye: the choroid rete mirabile, the lentiform body (also a rete), and the falciform process. When comparing the phyletically derived Antarctic clade exemplified by the families Artedidraconidae, Bathydraconidae, and Channichthyidae to the phyletically basal bovichtids, we observe phyletic regression and reduction in some regions of the brain and in some sensory modalities that are well displayed in bovichtids. In the phyletically derived families the brain is less cellular and nuclei are smaller and less prominent. In some species reduction in the size of the telencephalon, tectum, and corpus cerebelli imparts a "stalked" appearance to the brain with the neural axis visible between the reduced lobes. There is also a phyletic reduction in the number of ocular vascular structures from three in bovichtids to one or none in artedidraconids, bathydraconids, and channichthyids. There are no morphological features of bovichtid brains and sense organs that presage the divergence of the phyletically derived members of the clade in the Antarctic marine environment with its cold and deep continental shelves. We conclude that this environment does not require sensory or neural morphology or capabilities beyond those provided by the basic perciform body plan.

New radiotherapeutic technique for application of craniospinal target volume

To work out a craniospinal target volume definition and radiotherapy which can be used in clinical practice. This technique has been applied in the Municipal Center of Oncoradiology since 2004 for total cerebral and spinal (neuroaxis) radiation. The individual radiation treatment plans were carried out using the CadPlan (Varian) 3D planning system with linear accelerator, in 3D on the basis of CT. The CT slices were prepared at 1 cm distance. The target volume and the organs at risk (OAR) were marked in slices. To delineate the field asymmetrical blending and multileaf collimator (MLC) were applied. Depending on the shape and size of the target, two or more field matching were made with the new technique. The dose distribution in the target volume and the OAR were controlled in the coronary, sagittal and horizontal views and with dose volume histograms (DVH). The condition for applying this technique is the accurate adjustment of digital simulator picture, field-control picture and DRR (digital reconstructed radiogram).

Sonographic examination of the fetal central nervous system: guidelines for performing the ‘basic examination’ and the ‘fetal neurosonogram’

Sonographic examination of the fetal central nervous system: guidelines for performing the ‘basic examination’ and the ‘fetal neurosonogram’

Cognitive functions, bodily sensibility and the brain

Body representations traverse the whole of the brain. They provide vital sources of information for every facet of an animal’s behavior, and such direct neural connectivity of visceral input throughout the nervous system demonstrates just how strongly cognitive systems are linked to bodily representations. At each level of the neural axis there are visceral appraisal systems that are integral in the organization of action. Cognition is not one side of a divide and viscera the other, with action merely a reflexive outcome. There is no divide between cognition and bodily functions once the brain is involved. Cognitive mechanisms that permeate neural function are a cardinal piece of biological function and adaptation.

Impaired neural development caused by inducible expression of Axin in transgenic mice

Ablations of the Axin family genes demonstrated that they modulate Wnt signaling in key processes of mammalian development. The ubiquitously expressed Axin1 plays an important role in formation of the embryonic neural axis, while Axin2 is essential for craniofacial skeletogenesis. Although Axin2 is also highly expressed during early neural development, including the neural tube and neural crest, it is not essential for these processes, apparently due to functional redundancy with Axin1. To further investigate the role of Wnt signaling during early neural development, and its potential regulation by Axins, we developed a mouse model for conditional gene activation in the Axin2-expressing domains. We show that gene expression can be successfully targeted to the Axin2-expressing cells in a spatially and temporally specific fashion. High levels of Axin in this domain induce a region-specific effect on the patterning of neural tube. In the mutant embryos, only the development of midbrain is severely impaired even though the transgene is expressed throughout the neural tube. Axin apparently regulates β-catenin in coordinating cell cycle progression, cell adhesion and survival of neuroepithelial precursors during development of ventricles. Our data support the conclusion that the development of embryonic neural axis is highly sensitive to the level of Wnt signaling.

Threshold-Dependent BMP-Mediated Repression: A Model for a Conserved Mechanism That Patterns the Neuroectoderm

Subdivision of the neuroectoderm into three rows of cells along the dorsal-ventral axis by neural identity genes is a highly conserved developmental process. While neural identity genes are expressed in remarkably similar patterns in vertebrates and invertebrates, previous work suggests that these patterns may be regulated by distinct upstream genetic pathways. Here we ask whether a potential conserved source of positional information provided by the BMP signaling contributes to patterning the neuroectoderm. We have addressed this question in two ways: First, we asked whether BMPs can act as bona fide morphogens to pattern the Drosophila neuroectoderm in a dose-dependent fashion, and second, we examined whether BMPs might act in a similar fashion in patterning the vertebrate neuroectoderm. In this study, we show that graded BMP signaling participates in organizing the neural axis in Drosophila by repressing expression of neural identity genes in a threshold-dependent fashion. We also provide evidence for a similar organizing activity of BMP signaling in chick neural plate explants, which may operate by the same double negative mechanism that acts earlier during neural induction. We propose that BMPs played an ancestral role in patterning the metazoan neuroectoderm by threshold-dependent repression of neural identity genes.

Spinal Cord Monitoring in Patients With Spinal Deformity and Neural Axis Abnormalities

A retrospective review of spinal cord monitoring (SCM) results of patients with neural axis abnormalities (NAA) as compared with a control group of adolescent idiopathic scoliosis (AIS) patients. To analyze SCM on a group of patients who had a NAA undergoing spinal deformity surgery. To our knowledge, only 1 report in the literature has analyzed the accuracy and reliability of SCM in patients with NAA. Over a 10-year period, 41 patients with NAA had SCM while undergoing surgery for spinal deformity. These patients were retrospectively compared with a group of 136 AIS patients. The average ages were similar (14.4 vs. 14.6 years), but there were more males (48.8% vs. 19.1%) and greater preoperative curve magnitude in the NAA group (65.9 degrees vs. 59.8 degrees ) (P < 0.05). Good baseline values were achieved less often in the NAA group for somatosensory-evoked potentials (SSEP) (85.4% vs. 98.5%) and motor-evoked potentials (MEP) (82.6% vs. 100%) (P < 0.05). Significant deviations from baseline values were seen more often in the NAA group for SSEP (8.6% vs. 1.5%) and MEP (5.3% vs. 2.5%). There were no false negatives in either group. SCM in patients who have NAA can be more difficult to obtain than in AIS but results in few false positives and does not miss neurologic injury.