Differential regulation of FGF-2 in neurons and reactive astrocytes of axotomized rat hypoglossal nucleus. A possible therapeutic target for neuroprotection in peripheral nerve pathology

Despite the favorable treatment of cranial nerve neuropathology in adulthood, some cases are resistant to therapy leading to permanent functional impairments In many cases, suitable treatment is problematic as the therapeutic target remains unknown Basic fibroblast growth factor (bFGF, FGF 2) is involved in neuronal maintenance and wound repair following nervous system lesions It is one of few neurotrophic molecules acting in autocrine, paracrine and intracrine fashions depending upon specific circumstances Peripheral cranial somatic motor neurons, i e hypoglossal (XII) neurons, may offer a unique opportunity to study cellular FGF 2 mechanisms as the molecule is present in the cytoplasm of neurons and in the nuclei of astrocytes of the central nervous system FGF-2 may trigger differential actions during development, maintenance and lesion of XII neurons because axotomy of those cells leads to cell death during neonatal ages, but not in adult life Moreover, the modulatory effects of astroglial FGF 2 and the Ca+2 binding protein S100 beta have been postulated in paracrine mechanisms after neuronal lesions In our study, adult Wistar rats received a unilateral crush or transection (with amputation of stumps) of XII nerve, and were sacrificed after 72 h or 11 days Brains were processed for immunohistochemical localization of neurofilaments (NF), with or without counterstaining for Nissl substance, ghat fibrillary acidic protein (GFAP, as a marker of astrocytes), S100 beta and FGF-2 The number of Nissl positive neurons of axotomized XII nucleus did not differ from controls The NF immunoreactivity increased in the perikarya and decreased in the neuropil of axotomized XII neurons 11 days after nerve crush or transection An astrocytic reaction was seen in the ipsilateral XII nucleus of the crushed or transected animals 72 h and 11 days after the surgery The nerve lesions did not change the number of FGF-2 neurons in the ipsilateral XII nucleus, however, the nerve transection increased the number of FGF-2 ghat profiles by 72 h and 11 days Microdensitometric image analysis revealed a short lasting decrease in the intensity of FGF 2 immunoreactivity in axotomized XII neurons by 72 h after nerve crush or transection and also an elevation of FGF-2 in the ipsilateral of ghat nuclei by 72h and 11 days after the two lesions S100 beta decreased in astrocytes of 11-day transected XII nucleus The two-color immunoperoxidase for the simultaneous detection of the GFAP/FGF-2 indicated FGF-2 upregulation in the nuclei of reactive astrocytes of the lesioned XII nucleus Astroglial FGF-2 may exert paracrine trophic actions in mature axotomized XII neurons and might represent a therapeutic target for neuroprotection in peripheral nerve pathology (C) 2009 Elsevier GmbH All rights reserved

The reactions of specific neuron types to intestinal ischemia in the guinea pig enteric nervous system

Damage following ischemia and reperfusion (I/R) is common in the intestine and can be caused during abdominal surgery, in several disease states and following intestinal transplantation. Most studies have concentrated on damage to the mucosa, although published evidence also points to effects on neurons. Moreover, alterations of neuronally controlled functions of the intestine persist after I/R. The present study was designed to investigate the time course of damage to neurons and the selectivity of the effect of I/R damage for specific types of enteric neurons. A branch of the superior mesenteric artery supplying the distal ileum of anesthetised guinea pigs was occluded for 1 h and the animals were allowed to recover for 2 h to 4 weeks before tissue was taken for the immunohistochemical localization of markers of specific neuron types in tissues from sham and I/R animals. The dendrites of neurons with nitric oxide synthase (NOS) immunoreactivity, which are inhibitory motor neurons and interneurons, were distorted and swollen by 24 h after I/R and remained enlarged up to 28 days. The total neuron profile areas (cell body plus dendrites) increased by 25%, but the sizes of cell bodies did not change significantly. Neurons of type II morphology (intrinsic primary afferent neurons), revealed by NeuN immunoreactivity, were transiently reduced in cell size, at 24 h and 7 days. These neurons also showed signs of minor cell surface blebbing. Calretinin neurons, many of which are excitatory motor neurons, were unaffected. Thus, this study revealed a selective damage to NOS neurons that was observed at 24 h and persisted up to 4 weeks, without a significant change in the relative numbers of NOS neurons.

Effects of Ischemia and Reperfusion on P2X(2) Receptor Expressing Neurons of the Rat Ileum Enteric Nervous System

Purpose We investigated the effects of ischemia/reperfusion in the intestine (I/R-i) on purine receptor P2X(2)-immunoreactive (IR) neurons of the rat ileum. Methods The superior mesenteric artery was occluded for 45 min with an atraumatic vascular clamp and animals were sacrificed 4 h later. Neurons of the myenteric and submucosal plexuses were evaluated for immunoreactivity against the P2X(2) receptor, nitric oxide synthase (NOS), choline acetyl transferase (ChAT), calbindin, and calretinin. Results Following I/R-i, we observed a decrease in P2X(2) receptor immunoreactivity in the cytoplasm and surface membranes of neurons of the myenteric and submucosal plexuses. These studies also revealed an absence of calbindin-positive neurons in the I/R-i group. In addition, the colocalization of the P2X(2) receptor with NOS, ChAT, and calretinin immunoreactivity in the myenteric plexus was decreased following I/R-i. Likewise, the colocalization between P2X(2) and calretinin in neurons of the submucosal plexus was also reduced. In the I/R-i group, there was a 55.8% decrease in the density of neurons immunoreactive (IR) for the P2X(2) receptor, a 26.4% reduction in NOS-IR neuron, a 25% reduction in ChAT-IR neuron, and a 47% reduction in calretinin-IR neuron. The density of P2X(2) receptor and calretinin-IR neurons also decreased in the submucosal plexus of the I/R-i group. In the myenteric plexus, P2X(2)-IR, NOS-IR, ChAT-IR and calretinin-IR neurons were reduced in size by 50%, 49.7%, 42%, and 33%, respectively, in the I/R-i group; in the submucosal plexus, P2X(2)-IR and calretinin-IR neurons were reduced in size by 56% and 72.6%, respectively. Conclusions These data demonstrate that ischemia/reperfusion of the intestine affects the expression of the P2X(2) receptor in neurons of the myenteric and submucosal plexus, as well as density and size of neurons in this population. Our findings indicate that I/R-i induces changes in P2X(2)-IR enteric neurons that could result in alterations in intestinal motility.

The Central Nervous System as Target for Antihypertensive Actions of a Proline-Rich Peptide from Bothrops jararaca Venom

Pyroglutamyl proline-rich oligopeptides, present in the venom of the pit viper Bothrops jararaca (Bj-PROs), are the first described naturally occurring inhibitors of the angiotensin I-converting enzyme (ACE). The inhibition of ACE by the decapeptide Bj-PRO-10c (nervous system. In agreement with its supposed neuronal action, this peptide dose-dependently evoked elevations of intracellular calcium concentration ([Ca(2+)](i)) in primary culture from postnatal rat brain. The N-terminal sequence of the peptide was not essential for induction of calcium fluxes, while any changes of C-terminal Pro or Ile residues affected Bj-PRO-10c`s activity. Using calcium imaging by confocal microscopy and fluorescence imaging plate reader analysis, we have characterized Bj-PRO-10c-induced [Ca(2+)](i) transients in rat brain cells as being independent from bradykinin-mediated effects and ACE inhibition. Bj-PRO-10c induced pertussis toxin-sensitive G(i/o)-protein activity mediated through a yet unknown receptor, influx and liberation of calcium from intracellular stores, as well as reduction of intracellular cAMP levels. Bj-PRO-10c promoted glutamate and GABA release that may be responsible for its antihypertensive activity and its effect on HR. (C) 2010 International Society for Advancement of Cytometry

Fos-like immunoreactivity in central nervous system of mice simultaneously exposed to the elevated plus-maze and nociception

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Multicentric lymphoma with metastasis in the central nervous system in a dog

Linfoma multicêntrico foi diagnosticado em um cão com dois anos de idade que apresentava insuficiência respiratória, aumento de volume abdominal (ascite) e linfoadenopatia generalizada. O exame imunoistoquímico revelou origem de células T com expressão CD3+ e CD79-. Após cinco semanas, o cão apresentou déficits neurológicos progressivos, sendo identificada a presença de linfócitos neoplásicos no líquor. O exame histopatológico demonstrou invasão de células neoplásicas no baço, linfonodos, cérebro e cerebelo.

Role of nitric oxide and beta-adrenoceptors of the central nervous system on the salivary flow induced by pilocarpine injection into the lateral ventricle

Our studies have focused on the effect of L-NG-nitroarginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), and L-arginine, the substrate of NOS, on salivary secretion induced by the administration of pilocarpine into the lateral cerebral ventricle (LV) of rats. The present study has also investigated the role of the beta-adrenergic agonists and antagonist injected into LV on the salivary secretion elicited by the injection of pilocarpine into LV. Male Holtzmann rats with a stainless-steel cannula implanted into the LV were used. The amount of salivary secretion was studied over a 7-min period after injection of pilocarpine, isoproterenol, propranolol, salbutamol, salmeterol, L-NAME and L-arginine. The injection of pilocarpine (10, 20, 40, 80 and 160 mug/mul) into LV produced a dose-dependent increase in salivary secretion. The injection of L-NAME (40 mug/mul) into LV alone produced an increase in salivary secretion. The injection of L-NAME into LV previous to the injection of pilocarpine produced an increase in salivary secretion. L-Arginine (30 mug/mul) injected alone into LV produced no change in salivary secretion. L-Arginine injected into LV attenuated pilocarpine-induced salivary secretion. The isoproterenol (40 nmol/mul) injected into LV increased into LV increased the salivary secretion. When injected previous to pilocarpine at a dose of 20 and 40 mug/mul, isoproterenol produced and additive effect on pilocarpine-induced salivary secretion. The 40-nmol/mul dose of propranolol injected alone or previous to pilocarpine into LV attenuated the pilocarpine-induced salivary secretion. The injection of salbutamol (40 nmol/mul), a specific beta-2 agonist, injected alone into LV produced no change in salivary secretion and when injected previous to pilocarpine produced and increase in salivary secretion. The 40-nmol/mul dose of salmeterol, a long-acting beta-2 agonist, injected into LV alone or previous to pilocarpine produced no change in salivary secretion. The results have shown that central injections of L-NAME and L-arginine interfere with the salivary secretion, which implies that might participate in pilocarpine-induced salivary secretion. The interaction between cholinergic and beta-adrenergic receptors of the central nervous system (CNS) for the control of salivary secretion can also be postulated. (C) 2002 Elsevier B.V. All rights reserved.

Effects of seasonal variation on the central nervous system activity of Ocimum gratissimum L. essential oil

Ocimum gratissimum L. (Lamiaceae) and other species of the same genus are used as medicines to treat central nervous system (CNS) diseases, commonly encountered in warm regions of the world. The chemical composition of Ocimum gratissimum essential oil varies according to their chemotypes: timol, eugenol or geraniol. In this study, the essential oil type eugenol was extracted by hydrodistillation in each of the four seasons of the year. Activity upon CNS was evaluated in the open-field and rota-rod tests; sleeping time induced by sodium pentobarbital (PBS, 40 mg/kg, intraperitoneally, i.p.) and anticonvulsant activity against seizures induced by both pentylenetetrazole (PTZ; 85 mg/kg, s.c.) and maximal electroshock (MES, 50 mA, 0.11 s) were determined. Essential oils obtained in each season were effective in increasing the sleeping duration and a preparation obtained in Spring was able to protect animals against tonic seizures induced by electroshock. In each season, eugenol and 1,8-cineole were the most abundant compounds, and in Spring the essential oil presented the greatest relative percentage of sesquiterpenes, suggesting that these compounds could explain the differences observed in the biological activity in essential oils obtained in different seasons of the year. (c) 2005 Elsevier B.V.. All rights reserved.

Effect of thyroid hormone T3 on Myosin-Va expression in the central nervous system

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of Spider Venom Toxin PWTX-I (6-Hydroxytrypargine) on the Central Nervous System of Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Urocortin in the central nervous system of a primate (Cebus apella): Sequencing, immunohistochemical, and hybridization histochemical characterization

The urocortin (UCN)-like immunoreactivity and UCN mRNA distribution in various regions of the nonprimate mammalian brain have been reported. However, the Edinger-Westphal nucleus (EW) appears to be the only brain site where UCN expression is conserved across species. Although UCN peptides are present throughout vertebrate phylogeny, the functional roles of both UCN and EW remain poorly understood. Therefore, a study focused on UCN system organization in the primate brain is warranted. By using immunohistochemistry (single and double labeling) and in situ hybridization, we have characterized the organization of UCN-expressing cells and fibers in the central nervous system and pituitary of the capuchin monkey (Cebus apella). In addition, the sequence of the prepro-UCN was determined to establish the level of structural conservation relative to the human sequence. To understand the relationship of acetylcholine cells in the EW, a colocalization study comparing choline acetyltransferase (ChAT) and UCN was also performed. The cloned monkey prepro-UCN is 95% identical to the human preprohormone across the matched sequences. By using an antiserum raised against rat UCN and a probe generated from human cDNA, we found that the EW is the dominant site for UCN expression, although UCN mRNA is also expressed in spinal cord lamina IX. Labeled axons and terminals were distributed diffusely throughout many brain regions and along the length of the spinal cord. of particular interest were UCN-immunoreactive inputs to the medial preoptic area, the paraventricular nucleus of the hypothalamus, the oral part of the spinal trigeminal nucleus, the flocculus of the cerebellum, and the spinal cord laminae VII and X. We found no UCN hybridization signal in the pituitary. In addition, we observed no colocalization between ChAT and UCN in EW neurons. Our results support the hypothesis that the UCN system might participate in the control of autonomic, endocrine, and sensorimotor functions in primates.

LOSS OF THE SEX-CHROMOSOME IN HUMAN NEOPLASIAS OF THE NERVOUS-SYSTEM

Thirty-eight tumors (five grade I-II astrocytomas, three grade III astrocytomas, four glioblastomas, one oligodendroglioma, four ependymomas, one pineocytoma, three medulloblastomas, four acoustic nerve neurinomas, one intraspinal neurinoma, one neurofibroma, 10 meningiomas, and one craniopharyngioma) and three benign lesions of the nervous system were evaluated cytogenetically after in vitro culture. Sex chromosome loss was detected in 56% of the cases (-X in 13 of the 25 female patients and -Y in nine of the 16 male patients). The objective of the present report was to study the role of this abnormality in cells of the nervous system.