Programming peculiarities in two cochlear implant users with superficial siderosis of the central nervous system

To report the audiological outcomes of cochlear implantation in two patients with severe to profound sensorineural hearing loss secondary to superficial siderosis of the CNS and discuss some programming peculiarities that were found in these cases. Retrospective review. Data concerning clinical presentation, diagnosis and audiological assessment pre- and post-implantation were collected of two patients with superficial siderosis of the CNS. Both patients showed good hearing thresholds but variable speech perception outcomes. One patient did not achieve open-set speech recognition, but the other achieved 70% speech recognition in quiet. Electrical compound action potentials could not be elicited in either patient. Map parameters showed the need for increased charge. Electrode impedances showed high longitudinal variability. The implants were fairly beneficial in restoring hearing and improving communication abilities although many reprogramming sessions have been required. The hurdle in programming was the need of frequent adjustments due to the physiologic variations in electrical discharges and neural conduction, besides the changes in the impedances. Patients diagnosed with superficial siderosis may achieve limited results in speech perception scores due to both cochlear and retrocochlear reasons. Careful counseling about the results must be given to the patients and their families before the cochlear implantation indication.

JC virus-associated central nervous system diseases in HIV-infected patients in Brazil: clinical presentations, associated factors with mortality and outcome

Introduction: Several presentations of neurologic complications caused by JC virus (JCV) in human immunodeficiency virus (HIV)-infected patients have been described and need to be distinguished from the "classic" form of progressive multifocal leukoencephalopathy (PML). The objectives of this study were: 1) to describe the spectrum and frequency of presentations of JCV-associated central nervous system (CNS) diseases; 2) identify factors associated with in-hospital mortality of patients with JCV-associated CNS disease; and 3) to estimate the overall mortality of this population. Material and methods: This was a retrospective study of HIV-infected patients admitted consecutively for JCV-associated CNS diseases in a referral teaching center in Sao Paulo, Brazil, from 2002 to 2007. All patients with laboratory confirmed JCV-associated CNS diseases were included using the following criteria: compatible clinical and radiological features associated with the presence of JCV DNA in the cerebrospinal fluid. JCV-associated CNS diseases were classified as follows: 1) classic PML; 2) inflammatory PML; and 3) JC virus granule cell neuronopathy (GCN). Results: We included 47 cases. JCV-associated CNS diseases were classified as follows: 1) classic PML: 42 (89%); 2) inflammatory PML: three (6%); and 3) JC virus GCN: four (9%). Nosocomial pneumonia (p = 0.003), previous diagnosis of HIV infection (p = 0.03), and imaging showing cerebellar and/or brainstem involvement (p = 0.02) were associated with in-hospital mortality. Overall mortality during hospitalization was 34%. Conclusions: Novel presentations of JCV-associated CNS diseases were observed in our setting; nosocomial pneumonia, previous diagnosis of HIV infection, and cerebellar and/or brainstem involvement were associated with in-hospital mortality; and overall mortality was high. (C) 2012 Elsevier Editora Ltda. All rights reserved.

Central nervous system of Rhipicephalus sanguineus ticks (Acari: Ixodidae): an ultrastructural study

This study performed the ultrastructural description of the synganglion of Rhipicephalus sanguineus males and females, aiming to contribute to the understanding of the cellular organization of this organ. The results show that the central nervous system of these individuals consists of a mass of fused nerves, named synganglion, from where nerves emerge towards several parts of the body. It is surrounded by the neural lamella, a uniform and acellular layer, constituted by repeated layers of homogeneous and finely granular material. The perineurium is just below, composed of glial cells, which extensions invaginate throughout the nervous tissue. The synganglion is internally divided into an outer cortex, which contains the cellular bodies of the neural cells and an inner neuropile. The neural cells can be classified into two types according to cell size, cytoplasm-nucleus relation, and neurosecretory activity. Type I cells are oval or spherical and present a large nucleus occupying most part of the cytoplasm, which contains few organelles. Type 2 cells are polygonal, present a great cytoplasm volume, and their nuclei are located in the cell periphery. The cytoplasm of these cells contains a well-developed rough endoplasmic reticulum, Golgi regions, mitochondria, and several neurosecretory granules. The subperineurium and the tracheal ramifications are found between the cortex and the neuropile. The latter is formed mainly by neural fibers, tracheal elements, and glial cells. The results obtained show that R. sanguineus males' and females' nervous tissue present an ultrastructural organization similar to the one described in the literature for other tick species.

Human Endometrial-Derived Mesenchymal Stem Cells Suppress Inflammation in the Central Nervous System of EAE Mice

FAPESP [2009/13109-5]

Successful Strategy for Targeting the Central Nervous System Using Magnetic Albumin Nanospheres

This study reports on the successful use of magnetic albumin nanosphere (MAN), consisting of maghemite nanoparticles hosted by albumin-based nanosphere, to target different sites within the central nervous system (CNS). Ultrastructural analysis by transmission electron microscopy (TEM) of the material collected from the mice was performed in the time window of 30 minutes up to 30 days after administration. Evidence found that the administered MAN was initially internalized and transported by erythrocytes across the blood-brain-barrier and transferred to glial cells and neuropils before internalization by neurons, mainly in the cerebellum. We hypothesize that the efficiency of MAN in crossing the BBB with no pathological alterations is due to the synergistic effect of its two main components, the iron-based nanosized particles and the hosting albumin-based nanospheres. We found that the MAN in targeting the CNS represents an important step towards the design of nanosized materials for clinical and diagnostic applications.

The sympathetic nervous system regulates the three glycerol-3P generation pathways in white adipose tissue of fasted, diabetic and high-protein diet-fed rats

The aim of the present study was to investigate the participation of the sympathetic nervous system (SNS) in the control of glycerol-3-P (G3P) generating pathways in white adipose tissue (WAT) of rats in three situations in which the plasma insulin levels are low. WAT from 48 h fasted animals, 3 day-streptozotocin diabetic animals and high-protein, carbohydrate-free (HP) diet-fed rats was surgical denervated and the G3P generation pathways were evaluated. Food deprivation, diabetes and the HP diet provoke a marked decrease in the rate of glucose uptake and glycerokinase (GyK) activity, but a significant increase in the glyceroneogenesis, estimated by the phosphoenolpyruvate carboxykinase (PEPCK) activity and the incorporation of 1-[C-14]-pyruvate into glycerol-TAG. The denervation provokes a reduction (similar to 70%) in the NE content of WAT in fasted, diabetic and HP diet-fed rats. The denervation induced an increase in WAT glucose uptake of fed, fasted, diabetic and HP diet-fed rats (40%, 60%, 3.2 fold and 35%, respectively). TAG-glycerol synthesis from pyruvate was reduced by denervation in adipocytes of fed (58%) and fasted (36%), saline-treated (58%) and diabetic (23%), and HP diet-fed rats (11%). In these same groups the denervation reduced the PEPCK mRNA expression (75%-95%) and the PEPCK activity (35%-60%). The denervation caused a similar to 35% decrease in GyK activity of control rats and a further similar to 35% reduction in the already low enzyme activity of fasted, diabetic and HP diet-fed rats. These data suggest that the SNS plays an important role in modulating G3P generating pathways in WAT, in situations where insulin levels are low. (C) 2012 Elsevier Inc. All rights reserved.

Central leptin replacement enhances chemorespiratory responses in leptin-deficient mice independent of changes in body weight

Previous studies showed that leptin-deficient (ob/ob) mice develop obesity and impaired ventilatory responses to CO2 . In this study, we examined if leptin replacement improves chemorespiratory responses to hypercapnia (7 % CO2) in ob/ob mice and if these effects were due to changes in body weight or to the direct effects of leptin in the central nervous system (CNS). was measured via plethysmography in obese leptin-deficient- (ob/ob) and wild-type- (WT) mice before and after leptin (10 mu g/2 mu l day) or vehicle (phosphate buffer solution) were microinjected into the fourth ventricle for four consecutive days. Although baseline was similar between groups, obese ob/ob mice exhibited attenuated compared to WT mice (134 +/- 9 versus 196 +/- 10 ml min(-1)). Fourth ventricle leptin treatment in obese ob/ob mice significantly improved (from 131 +/- 15 to 197 +/- 10 ml min(-1)) by increasing tidal volume (from 0.38 +/- 0.03 to 0.55 +/- 0.02 ml, vehicle and leptin, respectively). Subcutaneous leptin administration at the same dose administered centrally did not change in ob/ob mice. Central leptin treatment in WT had no effect on . Since the fourth ventricle leptin treatment decreased body weight in ob/ob mice, we also examined in lean pair-weighted ob/ob mice and found it to be impaired compared to WT mice. Thus, leptin deficiency, rather than obesity, is the main cause of impaired in ob/ob mice and leptin appears to play an important role in regulating chemorespiratory response by its direct actions on the CNS.

Hypoactivity of the central dopaminergic system and autistic-like behavior induced by a single early prenatal exposure to lipopolysaccharide

The aim of the present study was to evaluate the behavioral patterns associated with autism and the prevalence of these behaviors in males and females, to verify whether our model of lipopolysaccharide (LPS) administration represents an experimental model of autism. For this, we prenatally exposed Wistar rats to LPS (100 mu g/kg, intraperitoneally, on gestational day 9.5), which mimics infection by gram-negative bacteria. Furthermore, because the exact mechanisms by which autism develops are still unknown, we investigated the neurological mechanisms that might underlie the behavioral alterations that were observed. Because we previously had demonstrated that prenatal LPS decreases striatal dopamine (DA) and metabolite levels, the striatal dopaminergic system (tyrosine hydroxylase [TH] and DA receptors D1a and D2) and glial cells (astrocytes and microglia) were analyzed by using immunohistochemistry, immunoblotting, and real-time PCR. Our results show that prenatal LPS exposure impaired communication (ultrasonic vocalizations) in male pups and learning and memory (T-maze spontaneous alternation) in male adults, as well as inducing repetitive/restricted behavior, but did not change social interactions in either infancy (play behavior) or adulthood in females. Moreover, although the expression of DA receptors was unchanged, the experimental animals exhibited reduced striatal TH levels, indicating that reduced DA synthesis impaired the striatal dopaminergic system. The expression of glial cell markers was not increased, which suggests that prenatal LPS did not induce permanent neuroinflammation in the striatum. Together with our previous finding of social impairments in males, the present findings demonstrate that prenatal LPS induced autism-like effects and also a hypoactivation of the dopaminergic system. (c) 2012 Wiley Periodicals, Inc.

Medial prefrontal cortex endocannabinoid system modulates baroreflex activity through CB1 receptors

Ferreira-Junior NC, Fedoce AG, Alves FHF, Correa FMA, Resstel LBM. Medial prefrontal cortex endocannabinoid system modulates baroreflex activity through CB1 receptors. Am J Physiol Regul Integr Comp Physiol 302: R876-R885, 2012. First published December 28, 2011; doi: 10.1152/ajpregu.00330.2011.-Neural reflex mechanisms, such as the baroreflex, are involved in the regulation of cardiovascular system activity. Previous results from our group (Resstel LB, Correa FM. Medial prefrontal cortex NMDA receptors and nitric oxide modulate the parasympathetic component of the baroreflex. Eur J Neurosci 23: 481-488, 2006) have shown that glutamatergic synapses in the ventral portion of the medial prefrontal cortex (vMPFC) modulate baroreflex activity. Moreover, glutamatergic neurotransmission in the vMPFC can be modulated by the endocannabinoids system (eCBs), particularly the endocannabinoid anandamide, through presynaptic CB1 receptor activation. Therefore, in the present study, we investigated eCBs receptors that are present in the vMPFC, and more specifically whether CB1 receptors modulate baroreflex activity. We found that bilateral microinjection of the CB1 receptor antagonist AM251 (100 or 300 pmol/200 nl) into the vMPFC increased baroreflex activity in unanesthetized rats. Moreover, bilateral microinjection of either the anandamide transporter inhibitor AM404 (100 pmol/200 nl) or the inhibitor of the enzyme fatty acid amide hydrolase that degrades anandamide, URB597 (100 pmol/200 nl), into the MPFC decreased baroreflex activity. Finally, pretreatment of the vMPFC with an ineffective dose of AM251 (10 pmol/200 nl) was able to block baroreflex effects of both AM404 and URB597. Taken together, our results support the view that the eCBs in the vMPFC is involved in the modulation of baroreflex activity through the activation of CB1 receptors, which modulate local glutamate release.

Central poststroke pain: somatosensory abnormalities and the presence of associated myofascial pain syndrome

Background: Central post-stroke pain (CPSP) is a neuropathic pain syndrome associated with somatosensory abnormalities due to central nervous system lesion following a cerebrovascular insult. Post-stroke pain (PSP) refers to a broader range of clinical conditions leading to pain after stroke, but not restricted to CPSP, including other types of pain such as myofascial pain syndrome (MPS), painful shoulder, lumbar and dorsal pain, complex regional pain syndrome, and spasticity-related pain. Despite its recognition as part of the general PSP diagnostic possibilities, the prevalence of MPS has never been characterized in patients with CPSP patients. We performed a cross-sectional standardized clinical and radiological evaluation of patients with definite CPSP in order to assess the presence of other non-neuropathic pain syndromes, and in particular, the role of myofascial pain syndrome in these patients. Methods: CPSP patients underwent a standardized sensory and motor neurological evaluation, and were classified according to stroke mechanism, neurological deficits, presence and profile of MPS. The Visual Analogic Scale (VAS), McGill Pain Questionnaire (MPQ), and Beck Depression Scale (BDS) were filled out by all participants. Results: Forty CPSP patients were included. Thirty-six (90.0%) had one single ischemic stroke. Pain presented during the first three months after stroke in 75.0%. Median pain intensity was 10 (5 to 10). There was no difference in pain intensity among the different lesion site groups. Neuropathic pain was continuous-ongoing in 34 (85.0%) patients and intermittent in the remainder. Burning was the most common descriptor (70%). Main aggravating factors were contact to cold (62.5%). Thermo-sensory abnormalities were universal. MPS was diagnosed in 27 (67.5%) patients and was more common in the supratentorial extra-thalamic group (P <0.001). No significant differences were observed among the different stroke location groups and pain questionnaires and scales scores. Importantly, CPSP patients with and without MPS did not differ in pain intensity (VAS), MPQ or BDS scores. Conclusions: The presence of MPS is not an exception after stroke and may present in association with CPSP as a common comorbid condition. Further studies are necessary to clarify the role of MPS in CPSP.