Estudo do envolvimento da neurotransmissão noradrenérgica do córtex pré-frontal medial nas respostas autonômicas desencadeadas pelo estresse por restrição agudo em ratos

O córtex pré-frontal medial (CPFM) é uma região límbica envolvida no controle da atividade autonômica e cardiovascular. Foi demonstrado que a inibição da região infra-límbica (IL) do CPFM reduziu as repostas comportamentais, neuroendócrinas e autônomas induzidas por estímulos aversivos. Entretanto, apesar das evidências de um importante papel do córtex IL na integração das respostas ao estresse, informações sobre os mecanismos neuroquímicos locais envolvidos no controle destas respostas ainda são escassos. Diante disso, o presente estudo teve o objetivo de investigar um possível envolvimento de mecanismos noradrenérgicos do córtex IL nas respostas autonômicas ao estresse por restrição agudo em ratos. Para tanto, nós investigamos, em grupos independentes de animais, o efeito da microinjeção bilateral no córtex IL de veículo (salina, 100nL), WB4101 (antagonista seletivo de adrenoceptores α1), RX821002 (antagonista seletivo de adrenoceptores α2) e propranolol (antagonista não-seletivo de adrenoceptores β, 10nmol/100nL), sobre as respostas de aumento da pressão arterial (PA) e frequência cardíaca (FC) e redução da temperatura cutânea da cauda induzidas pelo estresse por restrição agudo em ratos. A microinjeção bilateral de WB4101, RX821002 e propranolol no córtex IL não afetou os parâmetros basais de PA, FC e temperatura cutânea da cauda, o que indica uma ausência de influência na manutenção tônica do sistema cardiovascular. Entretanto, o bloqueio de adrenoceptores α1 no córtex IL diminuiu a resposta taquicárdica induzida pelo estresse por restrição, sem afetar as respostas pressora e de redução da temperatura cutânea da cauda. O bloqueio de adrenoceptores α2 no córtex IL reduziu todos os parâmetros analisados e o bloqueio de adrenoceptores β no córtex IL atenuou a resposta de redução da temperatura cutânea induzida pelo estresse por restrição. As respostas de elevação da ...

Efeitos ansiogênicos do óxido nítrico no córtex pre-frontal medial de camundongos

Medo e a ansiedade são emoções que têm origem nas reações de defesa que os animais exibem diante de ameaças que podem comprometer sua integridade física ou a própria sobrevivência, tais como confrontos com o predador ou com animais da mesma espécie. Em se tratando da espécie humana, estas respostas defensivas eliciadas representariam a ocorrência de transtornos de ansiedade e, a busca por sua compreensão, resultou no desenvolvimento de modelos animais de ansiedade, dentre os quais se destaca o labirinto em cruz elevado (LCE) que é baseado na aversão natural de roedores a espaços abertos. Com relação aos substratos neurais envolvidos nestas manifestações, cabe destacar a matéria cinzenta periaquedutal bem como estruturas prosencefálicas, como o córtex pré-frontal (CPFm), uma estrutura límbica que tem sido frequentemente descrita como relevante na neurobiologia da ansiedade. O óxido nítrico (NO) tem sido investigado em diferentes estruturas cerebrais de roedores nas quais foram evidenciadas respostas pró-aversivas. Sendo o CPFm uma estrutura que contém neurônios nitrérgicos, este estudo teve o objetivo de investigar o efeito da facilitação nitrérgica através da injeção intra-CPFm de um doador de NO, o NOC-9 [6-(Hidroxi-1-metil-2-nitrosohidrazino)-N-metil-1-hexanamina], sobre o comportamento de camundongos expostos ao labirinto em cruz elevado (LCE). Métodos e Resultados: Camundongos Suíços machos (25-35g, n = 53) receberam implante de cânula guia no CPFm. Cinco dias após, os animais receberam microinjeção de veículo ou NOC-9 nas doses de (1,875 nmol; 18,75 nmol; 37,5 nmol ou 75nmol) e, após cinco minutos, foram expostos... (Resumo completo, clicar acesso eletrônico abaixo)

Reconstruction of the anterior wall of the frontal sinus using bovine bone matrix: histological study with monkeys

The purpose of this study was to evaluate the repair process in the reconstruction of the anterior wall of the frontal sinus of monkeys with bovine bone matrix. Four adult Cebus apella monkeys underwent an ostectomy of the anterior wall of the frontal sinus. The frontal sinus mucosa and the nasofrontal duct were not manipulated. Reconstruction occurred with implants of bovine bone matrix laminae measuring 2.0 x 2.5 cm and 0.4 mm thick, stabilized under pressure in the lateral wall of the frontal sinus. The monkeys were sacrificed over a period of 150 days and routine laboratory procedures were followed for hematoxylin-eosin staining and histologic evaluation of the specimens. Neoformed bone tissue was observed in contact with the frontal sinus mucosa and the bovine bone matrix. The frontal sinus mucosa remained whole without fibrous tissue or cystic formations. There was no occurrence of cellularization as well as revascularization of the bovine bone matrix, though it has permitted bone conduction on this surface. It was possible to conclude that the demineralized bovine bone matrix was biotolerable, being incorporated into the bone without the presence of inflammatory cells with characteristics of inertness and antigenicity and behaved as an osteoconductive material.

Frontal-orbital advancement for the management of anterior plagiocephaly

The main purposes of this manuscript are to provide an overview of various modalities of surgical correction of anterior plagiocephaly and to emphasize their differences with the classic open frontal-orbital advancement. Advancement of technology provides development of many other ways to achieve the same results. The authors describe the classic open frontal-orbital advancement and compare with other proposed techniques for correction of frontal plagiocephaly. The main limitation of the use of new forms of treatment of the anterior plagiocephaly is the age of the patient. There is still no consensus on criteria for quantitative evaluation of surgical results, and new forms of treatment do not present results with long follow-up. Frontal-orbital advancement is the preferred procedure to correct unicoronal synostosis due to its universal indication regardless of the age and degree of deformation of the anterior plagiocephaly.

The differential adhesion forces of anterior cruciate and medial collateral ligament fibroblasts: effects of tropomodulin, talin, vinculin, and alpha-actinin.

We have determined the effects of tropomodulin (Tmod), talin, vinculin, and alpha-actinin on ligament fibroblast adhesion. The anterior cruciate ligament (ACL), which lacks a functional healing response, and the medial collateral ligament (MCL), a functionally healing ligament, were selected for this study. The micropipette aspiration technique was used to determine the forces needed to separate ACL and MCL cells from a fibronectin-coated surface. Delivery of exogenous tropomodulin, an actin-filament capping protein, into MCL fibroblasts significantly increased adhesion, whereas its monoclonal antibody (mAb) significantly decreased cell adhesiveness. However, for ACL fibroblasts, Tmod significantly reduced adhesion, whereas its mAb had no effect. mAbs to talin, vinculin, and alpha-actinin significantly decreased the adhesion of both ACL and MCL cells with increasing concentrations of antibody, and also reduced stress fiber formation and cell spreading rate as revealed by immunofluorescence microscopy. Disruption of actin filament and microtubule assembly with cytochalasin D and colchicine, respectively, also significantly reduced adhesion in ACL and MCL cells. In conclusion, both ACL and MCL fibroblast adhesion depends on cytoskeletal assembly; however, this dependence differs between ACL and MCL fibroblasts in many ways, especially in the role of Tmod. These results add yet another possible factor in explaining the clinical differences in healing between the ACL and the MCL.

Influence of fetal tissue transplant on the morphology of the neuromuscular junctions of tibialis anterior and medial gastrocnemius following spinal transection in the rat

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Influence of fetal tissue transplant on the morphology of the neuromuscular junctions of tibialis anterior and medial gastrocnemius following spinal transection in the rat

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Cognitive control associated with irritability induction: an autobiographical recall fMRI study

OBJECTIVE: Despite the relevance of irritability emotions to the treatment, prognosis and classification of psychiatric disorders, the neurobiological basis of this emotional state has been rarely investigated to date. We assessed the brain circuitry underlying personal script-driven irritability in healthy subjects (n = 11) using functional magnetic resonance imaging. METHOD: Blood oxygen level-dependent signal changes were recorded during auditory presentation of personal scripts of irritability in contrast to scripts of happiness or neutral emotional content. Self-rated emotional measurements and skin conductance recordings were also obtained. Images were acquired using a 1,5T magnetic resonance scanner. Brain activation maps were constructed from individual images, and between-condition differences in the mean power of experimental response were identified by using cluster-wise nonparametric tests. RESULTS: Compared to neutral scripts, increased blood oxygen level-dependent signal during irritability scripts was detected in the left subgenual anterior cingulate cortex, and in the left medial, anterolateral and posterolateral dorsal prefrontal cortex (cluster-wise p-value < 0.05). While the involvement of the subgenual cingulate and dorsal anterolateral prefrontal cortices was unique to the irritability state, increased blood oxygen level-dependent signal in dorsomedial and dorsal posterolateral prefrontal regions were also present during happiness induction. CONCLUSION: Irritability induction is associated with functional changes in a limited set of brain regions previously implicated in the mediation of emotional states. Changes in prefrontal and cingulate areas may be related to effortful cognitive control aspects that gain salience during the emergence of irritability.

Anticipation of pain enhances the nociceptive transmission and functional connectivity within pain network in rats

Background: Expectation is a very potent pain modulator in both humans and animals. There is evidence that pain transmission neurons are modulated by expectation preceding painful stimuli. Nonetheless, few studies have examined the influence of pain expectation on the pain-related neuronal activity and the functional connectivity within the central nociceptive network. Results: This study used a tone-laser conditioning paradigm to establish the pain expectation in rats, and simultaneously recorded the anterior cingulate cortex (ACC), the medial dorsal thalamus (MD), and the primary somatosensory cortex (SI) to investigate the effect of pain expectation on laser-induced neuronal responses. Cross-correlation and partial directed coherence analysis were used to determine the functional interactions within and between the recorded areas during nociceptive transmission. The results showed that under anticipation condition, the neuronal activity to the auditory cue was significantly increased in the ACC area, whereas those to actual noxious stimuli were enhanced in all the recorded areas. Furthermore, neuronal correlations within and between these areas were significantly increased under conditions of expectation compared to those under non-expectation conditions, indicating an enhanced synchronization of neural activity within the pain network. In addition, information flow from the medial (ACC and MD) to the lateral (SI cortex) pain pathway increased, suggesting that the emotion-related neural circuits may modulate the neuronal activity in the somatosensory pathway during nociceptive transmission. Conclusion: These results demonstrate that the nociceptive processing in both medial and lateral pain systems is modulated by the expectation of pain.

PACAP stimulates dopamine neuronal activity in the medial basal hypothalamus and inhibits prolactin

In sheep intracerebroventricular injection of PACAP (10 nmol) significantly (P < 0.01) stimulated the levels of the dopamine metabolite DOPAC within the medial basal hypothalamus las measured by in vivo microdialysis) and this effect was temporally correlated with a significant (P < 0.05) suppression in peripheral prolactin concentrations. This result is in accord with the hypothesis that PACAP suppresses prolactin secretion from the anterior pituitary gland by stimulating dopamine release from tuberoinfundibular dopaminergic neurons. (C) 1998 Elsevier Science B.V.

A medial to lateral shift in pre-movement cortical activity in hemi-Parkinson's disease

Objective: Recent evidence suggests that cortical activity associated with voluntary movement is relatively shifted from medial to lateral premotor areas in Parkinson's disease. This shift occurs bilaterally even for unilateral responses. It is not clear whether the shift in processing reflects an overall change in movement strategy, thereby involving alternate cortical areas, or reflects a compensatory change whereby, given the appropriate conditions, less impaired cortical areas are able to provide a similar function in compensation for those areas which are more impaired. This issue was examined in patients with hemi-Parkinson's disease, in whom basal ganglia impairment is most pronounced in one hemisphere. Methods: Fourteen patients with hemi-Parkinson's disease and 15 age-matched control subjects performed a Go/NoGo finger movement task and the contingent negative variation (CNV) was recorded from 21 scalp positions. Results and conclusions: Maximal CNV amplitudes were found over central medial regions for control subjects, but were shifted more frontally for Parkinson's disease patients, reduced in amplitude over the midline and lateralized towards the side ipsilateral to the greatest basal ganglia impairment. This shift in cortical activity from medial to lateral areas in Parkinson's disease patients appears to reflect a compensatory mechanism operating predominantly on the side of greatest basal ganglia impairment. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

THE ANTERIOR CINGULATE CORTEX IS A TARGET STRUCTURE FOR THE ANXIOLYTIC-LIKE EFFECTS OF BENZODIAZEPINES ASSESSED BY REPEATED EXPOSURE TO THE ELEVATED PLUS MAZE AND FOS IMMUNOREACTIVITY

Prior experience with the elevated plus maze (EPM) increases the avoidance of rodents to the open arms and impairs the anxiolytic-like effects of benzodiazepines on the traditional behaviors evaluated upon re-exposure to the maze, a phenomenon known as one-trial tolerance. Risk assessment behaviors are also sensitive to benzodiazepines. During re-exposure to the maze, these behaviors reinstate the information-processing initiated during the first experience, and the detection of danger generates stronger open-arm avoidance. The present study investigated whether the benzodiazepine midazolam alters risk assessment behaviors and Fos protein distribution associated with test and retest sessions in the EPM. Naive or maze-experienced Wistar rats received either saline or midazolam (0.5 mg/kg i.p.) and were subjected to the EPM. Midazolam caused the usual effects on exploratory behavior, increasing exploratory activity of naive rats in the open arms and producing no effects on these conventional measures in rats re-exposed to the maze. Risk assessment behaviors, however, were sensitive to the benzodiazepine during both sessions, indicating anxiolytic-like effects of the drug in both conditions. Fos immunohistochemistry showed that midazolam injections were associated with a distinct pattern of action when administered before the test or retest session, and the anterior cingulate cortex, area 1 (Cg1), was the only structure targeted by the benzodiazepine in both situations. Bilateral infusions of midazolam into the Cg1 replicated the behavioral effects of the drug injected systemically, suggesting that this area is critically involved in the anxiolytic-like effects of benzodiazepines, although the behavioral strategy adopted by the animals appears to depend on the previous knowledge of the threatening environment. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

Functional MR Imaging of visuo-spatial network in Autism Spectrum Disorder

Individuals with Autism Spectrum Disorder (ASD) are generally thought to have impaired attentional and executive function upon which all their cognitive and behaviour functions are based. Mental Rotation is a recognized visuo-spatial task, involving spatial working memory, known to involve activation in the fronto-parietal networks. To elucidate the functioning of fronto-parietal networks in ASD, the aim of this study was to use fMRI techniques with a mental rotation task, to characterize the underlying functional neural system. Sixteen male participants (seven highfunctioning autism or Asperger's syndrome; nine ageand performance IQ-matched controls) underwent fMRI. Participants were presented with 18 baseline and 18 rotation trials, with stimuli rotated 3- dimensionaUy (45°-180°). Data were acquired on a 3- Tesla scanner. The most widely accepted area reported to be involved in processing of visuo-spatial information. Posterior Parietal Cortex, was found to be activated in both groups, however, the ASD group showed decreased activation in cortical and subcortical frontal structures that are highly interconnected, including lateral and medial Brodmann area 6, frontal eye fields, caudate, dorsolateral prefrontal cortex and anterior cingulate. The suggested connectivity between these regions indicates that one or more circuits are impaired as a result of the disorder. In future it is hoped that we are able to identify the possible point of origin of this dysfunction, or indeed if the entire network is dysfunctional.

Lower N-Acetyl-Aspartate Levels in Prefrontal Cortices in Pediatric Bipolar Disorder: A (1)H Magnetic Resonance Spectroscopy Study

Objective: The few studies applying single-voxel(1)H spectroscopy in children and adolescents with bipolar disorder (BD) have reported low N-acetyl-aspartate (NAA) levels in the dorsolateral prefrontal cortex (DLPFC), and high myo-inositol / phosphocreatine plus creatine (PCr+Cr) ratios in the anterior cingulate. The aim of this study was to evaluate NAA, glycerophosphocholine plus phosphocholine (GPC+PC) and PCr+Cr in various frontal cortical areas in children and adolescents with BD. We hypothesized that NAA levels within the prefrontal cortex are lower in BD patients than in healthy controls, indicating neurodevelopmental alterations in the former. Method: We studied 43 pediatric patients with DSM-IV BD (19 female, mean age 13.2 +/- 2.9 years) and 38 healthy controls (79 female, mean age 13.9 +/- 2.7 years). We conducted multivoxel in vivo (1)H spectroscopy measurements at 1.5 Tesla using a long echo time of 272 ms to obtain bilateral metabolite levels from the medial prefrontal cortex (MPFC), DLPFC (white and gray matter), cingulate (anterior and posterior), and occipital lobes. We used the nonparametric Mann-Whitney U test to compare neurochemical levels between groups. Results: In pediatric BD patients, NAA and GPC+PC levels in the bilateral MPFC, and PCr+Cr levels in the left MPFC were lower than those seen in the controls. In the left DLPFC white matter, levels of NAA and PCr+Cr were also lower in BD patients than in controls. Conclusions: Lower NAA and PCr+Cr levels in the PFC of children and adolescents with BD may be indicative of abnormal dendritic arborization and neuropil, suggesting neurodevelopmental abnormalities. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(1):85-94.

The frontal assessment battery (FAB) reveals neurocognitive dysfunction in substance-dependent individuals in distinct executive domains: Abstract reasoning, motor programming, and cognitive flexibility

Substance-dependence is highly associated with executive cognitive function (ECF) impairments. However. considering that it is difficult to assess ECF clinically, the aim of the present study was to examine the feasibility of a brief neuropsychological tool (the Frontal Assessment Battery FAB) to detect specific ECF impairments in a sample of substance-dependent individuals (SDI). Sixty-two subjects participated in this study. Thirty DSM-IV-diagnosed SDI, after 2 weeks of abstinence, and 32 healthy individuals (control group) were evaluated with FAD and other ECF-related tasks: digits forward (DF), digits backward (DB), Stroop Color Word Test (SCWT), and Wisconsin Card Sorting Test (WCST). SDI did not differ from the control group on sociodemographic variables or IQ. However, SDI performed below the controls in OF, DB, and FAB. The SDI were cognitively impaired in 3 of the 6 cognitive domains assessed by the FAB: abstract reasoning, motor programming, and cognitive flexibility. The FAB correlated with DF, SCWT, and WCST. In addition, some neuropsychological measures were correlated with the amount of alcohol, cannabis, and cocaine use. In conclusion, SDI performed more poorly than the comparison group on the FAB and the FAB`s results were associated with other ECF-related tasks. The results suggested a negative impact of alcohol, cannabis, and cocaine use on the ECF. The FAB may be useful in assisting professionals as an instrument to screen for ECF-related deficits in SDI. (C) 2010 Elsevier Ltd. All rights reserved.