Early Regressive Development of the Subcommissural Organ of Two Human Fetuses with Non-Communicating Hydrocephalus.

Hydrocephalus is a central nervous system condition characterized by CSF buildup and ventricular hypertrophy. It is divided into two types: communicative and non-communicating hydrocephalus. Congenital hydrocephalus has been linked to several changes in the subcommissural organ (SCO). However, it is unclear whether these changes occur before or as a result of the hydrocephalic illness. This report presents three cases of human fetuses with hydrocephalus: one non-communicating case, two communicating cases, and two controls. Hematoxylin-Eosin (H&E) or cresyl violet and immunohistochemistry with anti-transthyretin were used to analyze SCO morphological and secretory changes. We conclude that in the cases presented here, there could be an early regression in the SCO of the communicating cases that is not present in the non-communicating case.

Brain sexual development in Kallmann syndrome

Prenatal and one-two month postnatal testosterone influences human neural and behavioural development, since the prenatal and one-two month postnatal hormone environment clearly contributes to the development of sex-related variation in human behaviour, and plays a role in the development of the sexual brain and individual differences in behaviour within each sex, as well as differences between the sexes. Olfactory system development, brain sexual maturation and sexual behaviour in man and animals are closely related. Kallmann syndrome (KS) is a genetic disorder which combines hypogonadotropic hypogonadism and anosmia. Hypogonadism is characterized by the absence or reduced levels of gonadotropinreleasing hormone, and anosmia is due to aplasia of the olfactory bulb. The overlap between the formation of the olfactory system and the migration of neurons that synthesize the gonadotropinreleasing hormone (GnRH) is common knowledge. GnRH neurons migrate from the medial portion of the nasal epithelium through the olfactory nerves and the main olfactory bulb to the anterior hypothalamus. Furthermore, the clinical manifestations of KS are: anosmia, the absence of puberty, and modifications in sexual behaviour. The structures responsible for the maturation of the main and accessory olfactory systems, the sexual differentiation of the brain and its relationship with clinical manifestations and sexual behaviour in Kallmann syndrome are analyzed in this review. The importance of the treatment of KS at early ages is suggested in order to improve brain sexual development and its clinical and sexual behaviour manifestations

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Expression of aquaporin-1 in the choroid plexus in communicating and non-communicating hydrocephalic rats

Hydrocephalus is an accumulation of cerebrospinal fluid (CSF) with dilatation of brain ventricles which can be either communicating or non-communicating. Multiple pathophysiological mechanisms underlie the appearance of hydrocephalus, which has many different causes including birth defects, brain hemorrhage, infection, meningitis, tumor, or head injury. The choroid plexuses (ChP) are circumventricular structures closely related to the above-mentioned pathophysiological mechanisms of the CSF, and aquaporin-1 (AQP1) is the water channel directly implicated in CSF production. Our studies with hydrocephalic rats revealed an increase and redistribution of AQP1 in the ChP, with AQP1 being expressed not only in the cell apical pole, but also in the cell basal pole and in the stroma. The immunohistochemical changes observed in both communicating and non-communicating hydrocephalus suggest a variation in the efficiency of the cells of the ChP, where AQP1 could perform both CSF production and reabsorption in order to delay ventricular dilatation

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The Neuroepithelium Disruption Could Generate Autoantibodies against AQP4 and Cause Neuromyelitis Optica and Hydrocephalus.

Neuromyelitis optica is an inflammatory disease characterized by neuritis and myelitis of the optic nerve. Its physiopathology is connected with the aquaporin-4 water channel, since antibodies against aquaporin-4 have been found in the cerebrospinal fluid and blood of neuromyelitis optica patients. The seropositivity for aquaporin-4 antibodies is used for the diagnosis of neuromyelitis optica or neuromyelitis optica spectrum disease. On the other hand, aquaporin-4 is expressed in astrocyte feet in the brain-blood barrier and subventricular zones of the brain ventricles. Aquaporin-4 expression is high in cerebrospinal fluid in hydrocephalus. Furthermore, neuroepithelial denudation precedes noncommunicating hydrocephalus and this neuroepithelial disruption could allow aquaporin-4 to reach anomalous brain areas where it is unrecognized and induce the generation of aquaporin-4 antibodies which could cause the neuromyelitis optica and certain types of hydrocephalus.

Early treatment of Kallmann syndrome may prevent eunuchoid appearance and behavior.

Kallmann syndrome (KS) is a genetic disorder which combines hypogonadotropic hypogonadism and anosmia. Hypogonadism is characterized by the absence or reduced levels of gonadotropin-releasing hormone and anosmia due to olfactory bulb aplasia. KS treatment usually begins just before puberty, but brain sexual maturation occurs long before puberty normally at perinatal age. As brain cells implicated in the development of the olfactory and reproductive system have a rostral and a caudal origin, and the rostral origin is affected by aplasia in KS and the caudal origin does not seem to be affected, the early treatment of KS, as proposed in this paper, is to attain brain sexual maturation at the most appropriate age possible to prevent the eunuchoid behavior and appearance observed in KS.

Aquaporin-4 expression in the cerebrospinal fluid in congenital human hydrocephalus.

BACKGROUND: Aquaporin-4 (AQP4) is a water channel mainly located in the ventricular ependymal cells (brain-CSF barrier), the sub-ependymal glia, glia limitans and in end-feet of astrocytes in at the blood-brain barrier (BBB). METHODS: In the present work, the expression of AQP4 in the cerebrospinal fluid (CSF) in control and congenital human hydrocephalus infants (obstructive and communicating), was analysed by Western-blot and enzyme immunoassay (ELISA). RESULTS: AQP4 was found to be high compared to the control in the CSF in congenital hydrocephalus patients. Western-blot showed higher values for AQP4 than controls in communicating hydrocephalus (communicating: 38.3%, control: 6.9% p < 0.05) although the increase was not significant in obstructive hydrocephalus (obstructive: 14.7%). The AQP4 quantification by ELISA also showed that, the mean concentration of AQP4 in CSF was significantly higher in communicating hydrocephalus (communicating: 11.32 ± 0.69 ng/ml, control: 8.61 ± 0.31 ng/ml; p < 0.05). However, there was no increase over control in obstructive hydrocephalus (obstructive: 8.65 ± 0.80 ng/ml). CONCLUSIONS: AQP4 has a modulatory effect on ependyma stability and acts in CSF production and reabsorption. Therefore, the increase of AQP4 in the CSF in congenital hydrocephalus could be due to the fact that AQP4 passes from the parenchyma to the CSF and this AQP4 movement may be a consequence of ependyma denudation.

What is relationship between the medial preoptic area, the organum vasculosum of the lamina terminalis and Kallmann syndrome?

The medial preoptic area is a structure located in the hypothalamic anteroventral third ventricle region, and is closely related to the olfactory brain development and sexual differentiation of the brain. The medial preoptic area surrounds the organum vasculosum of the lamina terminalis, and both structures are the main areas where synthesis of gonadotropin-releasing hormone occurs in the brain. Neurons synthesizing gonadotropin-releasing hormone migrate from the medial nasal epithelium to the rostral brain and reach the organum vasculosum of the lamina terminalis and the medial preoptic area. Kallmann syndrome is a genetic disorder which combines hypogonadotropic hypogonadism and anosmia. Hypogonadism is characterized by the absence or reduced levels of gonadotropin-releasing hormone and anosmia due to olfactory bulb aplasia. This paper speculates on the connection between the development of the medial preoptic area, the organum vasculosum of the lamina terminalis and olfactory bulbs with Kallmann syndrome, since the anteroventral third ventricle region is crucial for the normal development of these structures and its connection with the olfactory nerves and sexual maturation.

High blood pressure effects on the blood to cerebrospinal fluid barrier and cerebrospinal fluid protein composition: a two-dimensional electrophoresis study in spontaneously hypertensive rats.

The aim of the present work is to analyze the cerebrospinal fluid proteomic profile, trying to find possible biomarkers of the effects of hypertension of the blood to CSF barrier disruption in the brain and their participation in the cholesterol and ß-amyloid metabolism and inflammatory processes. Cerebrospinal fluid (CSF) is a system linked to the brain and its composition can be altered not only by encephalic disorder, but also by systemic diseases such as arterial hypertension, which produces alterations in the choroid plexus and cerebrospinal fluid protein composition. 2D gel electrophoresis in cerebrospinal fluid extracted from the cistern magna before sacrifice of hypertensive and control rats was performed. The results showed different proteomic profiles between SHR and WKY, that α-1-antitrypsin, apolipoprotein A1, albumin, immunoglobulin G, vitamin D binding protein, haptoglobin and α-1-macroglobulin were found to be up-regulated in SHR, and apolipoprotein E, transthyretin, α-2-HS-glycoprotein, transferrin, α-1ß-glycoprotein, kininogen and carbonic anhidrase II were down-regulated in SHR. The conclusion made here is that hypertension in SHR produces important variations in cerebrospinal fluid proteins that could be due to a choroid plexus dysfunction and this fact supports the close connection between hypertension and blood to cerebrospinal fluid barrier disruption.

Tibial marks in bare tibiae: relationship with robusticity indices

In bare bones, transverse lines may have several origins. Defleshing of a prey generates cutmarks, which can also appear in relation with traumatic events, post-mortem changes such as marks of animal teeth, rodent gnawing, or impact of stones, or even bone decoration. We hypothesize that in some instances they may be due to hyperplastic vessels beating on the bone surface, as expression of increased blood flow demand imposed by hypertrophied muscles. We analyzed 140 well-preserved tibiae which belonged to pre-Hispanic individuals from El Hierro, in the Canary Archipelago, currently kept at the Department of Archaeology and Prehistory of the University of La Laguna, and determined robusticity indices. Tibial marks were found in 53 out of 140 cases. Epiphyseal and diaphyseal robusticity indices were significantly higher in the first case among those with marks than among those without marks (T=3.13; p=0.002), and nearly significantly in the latter case (T=1.88; p=0.063). Considering only men, similar differences were observed regarding epiphyseal robusticity index (T=2.90; p=0.005) and diaphyseal robusticity index (T=2.11; p=0.039). There were also differences regarding the depth of the tibial marks: a higher epiphyseal robusticity index was associated with a more marked depth of the lines (T=2.11; p=0.042). An association was also observed between depth of the marks and sex (?2=4.12; p=0.042), more profound marks being observed among men. In conclusion, we here describe subtle bone marks in tibiae, which seem to correspond to vascular imprinting and are related to bone robustness. Whether or not they really represent an adaptation to an increased blood flow demand by hypertrophied muscles in relation with increased weight-bearing activity remains speculative, but this hypothesis may explain their presence (AU)

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Luteinizing hormone-releasing hormone distribution in the anterior hypothalamus of the female rats.

Luteinizing hormone-releasing hormone (LHRH) neurons and fibers are located in the anteroventral hypothalamus, specifically in the preoptic medial area and the organum vasculosum of the lamina terminalis. Most luteinizing hormone-releasing hormone neurons project to the median eminence where they are secreted in the pituitary portal system in order to control the release of gonadotropin. The aim of this study is to provide, using immunohistochemistry and female brain rats, a new description of the luteinizing hormone-releasing hormone fibers and neuron localization in the anterior hypothalamus. The greatest amount of the LHRH immunoreactive material was found in the organum vasculosum of the lamina terminalis that is located around the anterior region of the third ventricle. The intensity of the reaction of LHRH immunoreactive material decreases from cephalic to caudal localization; therefore, the greatest immunoreaction is in the organum vasculosum of the lamina terminalis, followed by the dorsomedial preoptic area, the ventromedial preoptic area, and finally the ventrolateral medial preoptic area, and in fibers surrounding the suprachiasmatic nucleus and subependymal layer on the floor of the third ventricle where the least amount immunoreactive material is found.

Immunohistochemical study of Pax6 and Reissner fibre expression in the prenatal development of the mouse subcommissural organ

The subcommissural organ (SCO) releases glycoproteins into the ventricular cerebrospinal fluid (CSF), where they form Reissner's fibre (RF) and also secretes a CSF-soluble material different from RF-material. Pax6 is a transcription factor important for the regulation of cell proliferation, migration and differentiation in the developing brain. In the present work, we studied wild-type, heterozygous and homozygous Sey mice to compare the expression of RF-antibody and Pax6 in the SCO and adjacent structures. In wild-type mice between E15 to E18, we observed Pax6 expression in cells surrounding the secretory cells of the SCO, and RF-immunoreactive material only in the SCO ependymal cell layer and its basal process. In the heterozygous mice, the neuroanatomical structure of the SCO was present, but RF-antibody staining and Pax6 expression was scarce or almost undetectable; in the homozygous mice neither SCO nor other epithalamic structures were found. We suggest that Pax6 expression at the periphery of the SCO is essential for the development and activity of the organ (AU)

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