Emilia M. Carmona-Calero

Alterations of the subcommissural organ in the hydrocephalic human fetal brain

We have studied the subcommissural organ of two hydrocephalic brains, of 20 and 21 gestational weeks and of two normal brains, aged 19 and 23 gestational weeks. Both hydrocephalic cases presented a size reduction of the subcommissural organ compared to the normal cases; only in one case, there were also alterations of the morphological components of the subcommissural organ, suggesting different pathogenic relationships between hydrocephalus and dysplasia of the subcommissural organ.

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

BackgroundAquaporin-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).MethodsIn 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).ResultsAQP4 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).ConclusionsAQP4 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.

Changes in the secretory activity of the subcommissural organ of spontaneously hypertensive rats

The subcommissural organ (SCO) is a glandular circumventricular organ secreting glycoproteins into the cerebrospinal fluid. The SCO of 15-week-old spontaneously hypertensive rats (SHR) and of matched normotensive Wistar-Kyoto rats (WKY) was studied immunocytochemically by using an antibody against the glycoproteins secreted by the SCO. The blood pressure, water intake and volume of brain ventricles of SHR and WKY rats were also recorded. The SHR were hypertensive, drank more water and did not display dilatation of the brain ventricles. The SCO of the SHR rats showed a drastic decrease of the immunoreactive material stored in the rough endoplasmic reticulum whereas the amount of immunoreactive apical secretory granules did not vary with respect to the SCO of WKY rats. These changes are compatible with an increased secretory activity of the SCO of the SHR rats. It is suggested that the changes in the SCO of SHR rats, and their hypertensive state, are interrelated phenomena.

Effects of chronic alcohol intake on the vasopressin content in the hypothalamic paraventricular and supraoptic nuclei of the mouse. An immunohistochemical and morphometric study

The present study analyses the response of the paraventricular (PVN) and supraoptic (SPO) nuclei of the hypothalamus of the male mouse to chronic alcohol intake by immunohistochemical and morphometric methods. We relate the intensity of the reaction to A-V with the vasopressin content of the nucleus, as all the slides, from the control and experimental groups, were processed at the same time and with the same solutions of the antibodies. We suggest that the accumulation of vasopressin, observed in the alcohol-treated animals, of both hypothalamic nuclei could be related to an inhibition of vasopressin release and/or transport from the SPO and PVN to the neurohypophysis and to an increase in vasopressin synthesis in the SPO as this nucleus shows an increase in its nuclear sizes, an index of the function of the neurons.

Alcohol Intake Effects on the Dorsal Vagal Complex of the Rat: A Cellular Morphometric Study

We have analyzed the morphometric effects on the dorsal vagal complex (DVC) of the rat of alcohol exposure and/or hypoproteic diet intake during 8 weeks. In the area postrema (AP), alcohol treatment (combined with normal isoproteic or hypoproteic diet) caused a significant decrease in karyometric parameters. In the dorsal motor nucleus of the vagus (DMV) and nucleus tractus solitari (NTS), the alcohol isoproteic intake (AI) produced an increase in neuron size (expressed by an increase in the neuronal nuclear area and the cell/neuropil coefficient). The hypoproteic diets produced a reduction in the global volume of each structure of the DVC which was accompanied by a decrease in global brain volume. These results indicate that after 8 weeks of treatment, alcohol is the main cause of the morphometric alteration found in the DVC, while variations in the amount of protein intake appear to produce global effects on the whole brain.

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.

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 β-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-1β-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.

Reissner's fibre proteins and p73 variations in the cerebrospinal fluid and subcommissural organ of hydrocephalic rat.

Reissner’s fibre (RF) is formed by the polymerization of the glycoprotein secreted by the subcommissural organ (SCO). The SCO also secretes soluble glycoprotein into the cerebrospinal fluid (CSF); variations in RF and SCO have been reported in hydrocephalus. On the other hand, hydrocephalus and other brain alterations have been described in p73 mutant mice. The p73 belongs to the tumour suppressor p53 protein family and has two isoforms: the TAp73 with apoptotic activity and ΔNp73 with anti‐apoptotic function. Moreover, the TAp73 isoform is glycosylated and secreted into the CSF. In the present work, we analysed the variations in RF and p73 proteins in the CSF and SCO of spontaneously hydrocephalic rats. Brains from control rats and spontaneously hydrocephalic rats of 12 months of age were used. The SCO sections were immunohistochemically processed with anti‐TAp73 and anti‐Reissner fibre (AFRU). The spontaneous hydrocephalus presents a decrease in the AFRU immunoreactive material in the SCO and an absence of RF. The anti‐TAp73 was also present, slightly decreased, in the hydrocephalic SCO. AFRU and p73 bands were also detected in the CSF by western blot and six AFRU and p73 protein bands of a similar molecular weight were found in the CSF of the control rats. The number of AFRU and p73 bands was lower in the hydrocephalic rats than in the control rats. In conclusion, hydrocephalus produces a decrease in the secretions of the SCO and an absence of RF and a decrease in p73 and RF proteins in the CSF.

Cerebrospinal fluid levels of tumor necrosis factor alpha and aquaporin 1 in patients with mild cognitive impairment and idiopathic normal pressure hydrocephalus

OBJECTIVE The aim of the present work was to make a comparative analysis of the cerebrospinal fluid levels of Tumor necrosis factor (TNFα) and aquaporin 1 (AQP1) in (i) healthy elder control, (ii) patients with mild cognitive impairment and, (iii) patients with idiopathic normal pressure hydrocephalus. PATIENTS AND METHODS Samples of CSF were taken from seven patients with MCI, 77 years average age; six patients with iNPH, 75 years average age; eleven healthy subjects, 60year average age, were used as controls. The cerebrospinal fluid levels of AQP1 and TNFα were studied by enzyme immunoassay (ELISA). RESULTS In mild cognitive impairment the total protein content of the CSF and the relative CSF levels of AQP1 and TNFα were similar to those of control subjects and different from those of iNPH patients. On the other hand, in iNPH patients the CSF content of proteins was low and the levels of TNFα were significantly high while those of AQP1 were insignificantly high. CONCLUSION These finding may help the differential diagnosis and prognosis of mild cognitive impairment and normal pressure hydrocephalus patients.

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.