Rapid eye movement (REM) sleep deprivation reduces rat frontal cortex acetylcholinesterase (EC 3.1.1.7) activity

Rapid eye movement (REM) sleep deprivation induces several behavioral changes. Among these, a decrease in yawning behavior produced by low doses of cholinergic agonists is observed which indicates a change in brain cholinergic neurotransmission after REM sleep deprivation. Acetylcholinesterase (Achase) controls acetylcholine (Ach) availability in the synaptic cleft. Therefore, altered Achase activity may lead to a change in Ach availability at the receptor level which, in turn, may result in modification of cholinergic neurotransmission. To determine if REM sleep deprivation would change the activity of Achase, male Wistar rats, 3 months old, weighing 250-300 g, were deprived of REM sleep for 96 h by the flower-pot technique (N = 12). Two additional groups, a home-cage control (N = 6) and a large platform control (N = 6), were also used. Achase was measured in the frontal cortex using two different methods to obtain the enzyme activity. One method consisted of the obtention of total (900 g supernatant), membrane-bound (100,000 g pellet) and soluble (100,000 g supernatant) Achase, and the other method consisted of the obtention of a fraction (40,000 g pellet) enriched in synaptic membrane-bound enzyme. In both preparations, REM sleep deprivation induced a significant decrease in rat frontal cortex Achase activity when compared to both home-cage and large platform controls. REM sleep deprivation induced a significant decrease of 16% in the membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) in the 100,000 g pellet enzyme preparation (home-cage group 152.1 ± 5.7, large platform group 152.7 ± 24.9 and REM sleep-deprived group 127.9 ± 13.8). There was no difference in the soluble enzyme activity. REM sleep deprivation also induced a significant decrease of 20% in the enriched synaptic membrane-bound Achase activity (home-cage group 126.4 ± 21.5, large platform group 127.8 ± 20.4, REM sleep-deprived group 102.8 ± 14.2). Our results suggest that REM sleep deprivation changes Ach availability at the level of its receptors through a decrease in Achase activity

Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

Spreading depression is facilitated in adult rats previously submitted to short episodes of malnutrition during the lactation period

Lactating rat dams were submitted to short episodes (1, 2 or 3 weeks) of nutritional restriction by receiving the "regional basic diet" (RBD, with 8% protein) of low-income human populations of Northeast Brazil. Their pups were then studied regarding the developmental effects on body and brain weights. When the rats reached adulthood, cortical susceptibility to the phenomenon of spreading depression (SD) was evaluated by performing electrophysiological recordings on the surface of the cerebral cortex. SD was elicited at 20-min intervals by applying 2% KCl for 1 min to a site on the frontal cortex and its occurrence was monitored at 2 sites in the parietal region by recording the electrocorticogram and the slow potential change of SD. When compared to control rats fed a commercial diet with 23% protein, early malnourished rats showed deficits in body and brain weights (10% to 60% and 3% to 15%, respectively), as well as increases in velocity of SD propagation (10% to 20%). These effects were directly related to the duration of maternal dietary restriction, with pups malnourished for 2 or 3 weeks presenting more intense weight and SD changes than those malnourished for 1 week. The effects of 1-week restrictions on SD were less evident in the pups malnourished during the second week of lactation and were more evident in pups receiving the RBD during the third week. The results indicate that short episodes of early malnutrition during the suckling period can affect body and brain development, as well as the cortical susceptibility to SD during adulthood. The data also suggest that the third week of lactation is the period during which the brain is most sensitive to malnutrition, concerning the effects on SD

Effect of policosanol on cerebral ischemia in Mongolian gerbils

Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane wax, whose main component is octacosanol. An inhibitory effect of policosanol on platelet aggregation and cerebral ischemia in animal models has been reported. Thus, the objective of the present study was to evaluate the effect of policosanol on cerebral ischemia induced by unilateral carotid ligation and bilateral clamping and recirculation in Mongolian gerbils. Policosanol (200 mg/kg) administered immediately after unilateral carotid ligation and at 12- or 24-h intervals for 48 h significantly inhibited mortality and clinical symptoms when compared with controls, whereas lower doses (100 mg/kg) were not effective. Control animals showed swelling (tissue vacuolization) and necrosis of neurons in all areas of the brain studied (frontal cortex, hippocampus, striatum and olfactory tubercle), showing a similar injury profile. In the group treated with 200 mg/kg policosanol swelling and necrosis were significantly reduced when compared with the control group. In another experimental model, comparison between groups showed that the brain water content of control gerbils (N = 15) was significantly higher after 15 min of clamping and 4 h of recirculation than in sham-operated animals (N = 13), whereas policosanol (200 mg/kg) (N = 19) significantly reduced the edema compared with the control group, with a cerebral water content identical to that of the sham-operated animals. cAMP levels in the brain of control-ligated Mongolian gerbils (N = 8) were significantly lower than those of sham-operated animals (N = 10). The policosanol-treated group (N = 10) showed significantly higher cAMP levels (2.68 pmol/g of tissue) than the positive control (1.91 pmol/g of tissue) and similar to those of non-ligated gerbils (2.97 pmol/g of tissue). In conclusion, our results show an anti-ischemic effect of policosanol administered after induction of cerebral ischemia, in two different experimental models in Mongolian gerbils, suggesting a possible therapeutic effect in cerebral vascular disorders.

Effects of septal cholinergic lesion on rat exploratory behavior in an open-field

The medial septum participates in the modulation of exploratory behavior triggered by novelty. Also, selective lesions of the cholinergic component of the septohippocampal system alter the habituation of rats to an elevated plus-maze without modifying anxiety indices. We investigated the effects of the intraseptal injection of the cholinergic immunotoxin 192 IgG-saporin (SAP) on the behavior of rats in an open-field. Thirty-nine male Wistar rats (weight: 194-230 g) were divided into three groups, non-injected controls and rats injected with either saline (0.5 µl) or SAP (237.5 ng/0.5 µl). Twelve days after surgery, the animals were placed in a square open-field (120 cm) and allowed to freely explore for 5 min. After the test, the rats were killed by decapitation and the septum, hippocampus and frontal cortex were removed and assayed for acetylcholinesterase activity. SAP increased acetylcholinesterase activity in the septum, hippocampus and frontal cortex and decreased the total distance run (9.15 ± 1.51 m) in comparison to controls (13.49 ± 0.91 m). The time spent in the center and at the periphery was not altered by SAP but the distance run was reduced during the first and second minutes (2.43 ± 0.36 and 1.75 ± 0.34 m) compared to controls (4.18 ± 0.26 and 3.14 ± 0.25 m). SAP-treated rats showed decreased but persistent exploration throughout the session. These results suggest that septohippocampal cholinergic mechanisms contribute to at least two critical processes, one related to the motivation to explore new environments and the other to the acquisition and storage of spatial information (i.e., spatial memory).

Absence-like seizures in adult rats following pilocarpine-induced status epilepticus early in life

Administration of pilocarpine causes epilepsy in rats if status epilepticus (SE) is induced at an early age. To determine in detail the electrophysiological patterns of the epileptogenic activity in these animals, 46 Wistar rats, 7-17 days old, were subjected to SE induced by pilocarpine and electro-oscillograms from the cortex, hippocampus, amygdala, thalamus and hypothalamus, as well as head, rostrum and vibrissa, eye, ear and forelimb movements, were recorded 120 days later. Six control animals of the same age range did not show any signs of epilepsy. In all the rats subjected to SE, iterative spike-wave complexes (8.1 ± 0.5 Hz in frequency, 18.9 ± 9.1 s in duration) were recorded from the frontal cortex during absence fits. However, similar spike-wave discharges were always found also in the hippocampus and, less frequently, in the amygdala and in thalamic nuclei. Repetitive or single spikes were also detected in these same central structures. Clonic movements and single jerks were recorded from all the rats, either concomitantly with or independently of the spike-wave complexes and spikes. We conclude that rats made epileptic with pilocarpine develop absence seizures also occurring during paradoxical sleep, showing the characteristic spike-wave bursts in neocortical areas and also in the hippocampus. This is in contrast to the well-accepted statement that one of the main characteristics of absence-like fits in the rat is that spike-wave discharges are never recorded from the hippocampal fields.

Interaction between affordance and handedness recognition: a chronometric study

The visualization of tools and manipulable objects activates motor-related areas in the cortex, facilitating possible actions toward them. This pattern of activity may underlie the phenomenon of object affordance. Some cortical motor neurons are also covertly activated during the recognition of body parts such as hands. One hypothesis is that different subpopulations of motor neurons in the frontal cortex are activated in each motor program; for example, canonical neurons in the premotor cortex are responsible for the affordance of visual objects, while mirror neurons support motor imagery triggered during handedness recognition. However, the question remains whether these subpopulations work independently. This hypothesis can be tested with a manual reaction time (MRT) task with a priming paradigm to evaluate whether the view of a manipulable object interferes with the motor imagery of the subject's hand. The MRT provides a measure of the course of information processing in the brain and allows indirect evaluation of cognitive processes. Our results suggest that canonical and mirror neurons work together to create a motor plan involving hand movements to facilitate successful object manipulation.

Proton magnetic resonance spectroscopy of the frontal, cingulate and perirolandic cortices and its relationship to skin conductance in patients with schizophrenia

The aim of the present study was to determine whether specific subgroups of schizophrenic patients, grouped according to electrodermal characteristics, show differences in the N-acetylaspartate/creatine plus choline (NAA / (Cr + Cho)) ratios in the frontal, cingulate and perirolandic cortices. Skin conductance levels (SCL) and skin conductance responses to auditory stimulation were measured in 38 patients with schizophrenia and in the same number of matched healthy volunteers (control). All subjects were submitted to multivoxel proton magnetic resonance spectroscopic imaging. When compared to the control group, patients presented significantly lower NAA / (Cr + Cho) ratios in the right dorsolateral prefrontal cortex (schizophrenia = 0.95 ± 0.03; control = 1.12 ± 0.04) and in the right (schizophrenia = 0.88 ± 0.02; control = 0.94 ± 0.03) and left (schizophrenia = 0.84 ± 0.03; control = 0.94 ± 0.03) cingulates. These ratios did not differ between electrodermally responsive and non-responsive patients. When patients were divided into two groups: lower SCL (less than the mean SCL of the control group minus two standard deviations) and normal SCL (similar to the control group), the subgroup with a lower level of SCL showed a lower NAA / (Cr + Cho) ratio in the left cingulate (0.78 ± 0.05) than the controls (0.95 ± 0.02, P < 0.05) and the subgroup with normal SCL (0.88 ± 0.03, P < 0.05). There was a negative correlation between the NAA / (Cr + Cho) ratio in the left cingulate of patients with schizophrenia and the duration of the disease and years under medication. These data suggest the existence of a schizophrenic subgroup characterized by low SCL that could be a consequence of the lower neuronal viability observed in the left cingulate of these patients.

Laringectomia frontal anterior: técnica de Tucker. Estudo retrospectivo

O carcinoma epidermóide da laringe é a sexta neoplasia mais comum, sendo uma das neoplasias malignas mais freqüentes na cabeça e pescoço, ocupando o segundo lugar imediatamente após o câncer da cavidade oral. FORMA DE ESTUDO: Estudo clínico retrospectivo. MATERIAL E MÉTODO: Entre os anos de 1991 e 2003, 24 pacientes portadores de lesões glóticas envolvendo a comissura anterior foram submetidos a laringectomia frontal anterior com epiglotoplastia descrita por Tucker e colaboradores no ano de 1979. RESULTADO: Nossos resultados confirmam aqueles encontrados em outras publicações. Não ocorreram mortes no pós-operatório e o seguimento foi relativamente simples. Todos os pacientes foram decanulizados e recuperaram um efetivo trato digestivo e aéreo. CONCLUSÃO: Nossos achados mostram que a laringectomia pela técnica de Tucker é uma cirurgia efetiva para o tratamento dos carcinomas glóticos que acometem a comissura anterior e a porção membranosa das cordas vocais com a motilidade preservada, pois tais lesões não devem ser tratadas pela ressecção endoscópica trans-oral ou por uma laringectomia fronto lateral.

O treinamento da operação osteoplástica usando o seio frontal do cão

O acesso ao seio frontal usando a técnica do retalho osteoplástico está indicada em lesões que não podem ser abordadas pela via endonasal. O aprendizado da técnica pode ser realizado em cães, mas a delimitação do seio do cão, de forma como se faz no homem, não é facilmente realizável. OBJETIVO: Apresentar um método de localização e delimitação do seio frontal do cão que permita reproduzir a técnica osteoplástica. FORMA DE ESTUDO: Técnica cirúrgica em animal. MATERIAL E MÉTODO: Em cães traçaram-se duas linhas retas, uma delas ao longo da linha média da região frontal, outra passando pela pupila, inclinada 45º em direção à linha anterior. No ponto de intersecção, mede-se um ou um centímetro e meio para frente e um centímetro para trás. A partir destas medidas desenha-se um retângulo incompleto que delineia os limites aproximados do seio frontal. RESULTADOS: O procedimento foi realizado 12 vezes com a participação de médicos residentes. O seio frontal foi aberto facilmente em todos os animais, reproduzindo a técnica osteoplástica sem erros de localização do seio. CONCLUSÃO: O método de localização e de limitação do seio frontal do cão mostrou-se útil no ensino da técnica osteoplástica de acesso por ser reproduzível de forma realística.

Cirurgia das fraturas do seio frontal: estudo epidemiológico e análise de técnicas

O trauma do seio frontal não é raro, correspondendo a 8% das fraturas faciais. Pode afetar a lâmina anterior e/ou posterior, com ou sem envolvimento do ducto nasofrontal. Tem alto potencial para complicações e seu manejo ainda é controvertido em algumas situações. OBJETIVO: Apresentar a epidemiologia, o diagnóstico e tratamento clínico e cirúrgico de 24 pacientes com fratura do seio frontal. MATERIAL E MÉTODOS: Estudo retrospectivo, não randomizado, de 24 pacientes com fratura de seio frontal operados no Hospital das Clínicas da Faculdade de Medicina de Botucatu, São Paulo, Brasil. RESULTADOS: Dos 24 pacientes, 16 tinham fraturas da lâmina externa e 8, da lâmina interna e externa. Em 2 casos havia lesão do ducto nasofrontal. Vinte (83,4%) pacientes tiveram fraturas faciais associadas e em 13 (54,2%) foram observadas complicações intracranianas. A incisão em asa de borboleta, abaixo da sobrancelha, foi empregada na maioria dos casos cirúrgicos com bom resultado estético. Fixação dos fragmentos ósseos com diferentes materiais (fio de aço, mononylon, miniplacas de titânio) e, se necessário, reconstrução da tábua anterior com material aloplástico ou osso parietal. CONCLUSÃO: A causa principal das fraturas do seio frontal é acidente com veículos. O tratamento depende de sua complexidade, pois comumente há lesões cranioencefálicas associadas. As técnicas cirúrgicas utilizadas são as incisões, retalho bicoronal ou na sobrancelha, infra-orbital (em asa de borboleta), associadas à cirurgia endoscópica em casos de infecção fístula liquórica e complicações orbitárias.

A Trefinação do Seio Frontal deve ser sempre realizada a 1cm da linha média? Um estudo tomográfico

A complexa anatomia do recesso frontoetmoidal, bem como sua relação anatômica com estruturas vitais, explicam a razão do considerável cuidado que se tem durante a cirurgia para preservar estas estruturas e minimizar complicações relacionadas ao processo de cicatrização. A trefinação é um procedimento amplamente aceito para acesso ao seio frontal. OBJETIVO: Avaliar o melhor ponto para se realizar a trefinação do seio frontal. MÉTODOS: Mensuração da profundidade do seio frontal em 3 pontos eqüidistantes da linha média (crista galli) em cortes tomográficos axiais. RESULTADOS: Foram medidos 138 seios frontais (69 pacientes). A profundidade do seio frontal medida a 0,5cm da linha média foi significativamente maior do que a 1,0 e 1,5cm, assim como a medida a 1,0cm foi significativamente maior do que a 1,5cm (12,22±4,25 vs 11,78±4,65 p<0,05; 12,22±4,25 vs 10,78±5,98 p<0,001; 11,78±4,65 vs 10,78±5,98 p<0,05). O trefinador usado (penetração máxima de 0,7cm) é seguro de ser usado em cerca de 80% dos pacientes. CONCLUSÃO: A trefinação pode ser realizada em pontos variáveis do seio frontal, mas a distância de 1cm da linha média parece ser mais segura e apresentar resultados estéticos melhores.

Estudo da anatomia do recesso frontal por meio de dissecção endoscópica em cadáveres

INTRODUÇÃO E OBJETIVO: O óstio do seio frontal freqüentemente apresenta difícil reconhecimento devido a estruturas anatômicas que encobrem sua visibilização. O objetivo principal desse estudo foi identificar e descrever as estruturas anatômicas do recesso frontal que dificultam o reconhecimento do óstio do seio frontal. CASUÍSTICA E MÉTODOS: Foi realizado um estudo prospectivo por meio de dissecção endoscópica consecutiva de 32 cadáveres (59 fossas nasais), 10 (31,25%) do sexo feminino e 22 (68,75%) do sexo masculino. Após exérese endoscópica da porção inferior do processo uncinado, com a preservação da sua inserção superior, avaliamos quais estruturas anatômicas necessitavam ser removidas até a completa visibilização endonasal do óstio do seio frontal. RESULTADOS E CONCLUSÃO: A visibilização do óstio do seio frontal após a exérese da porção inferior do processo uncinado foi possível em apenas 11 (18,64%) fossas nasais. O processo uncinado (recesso terminal) representou a principal estrutura anatômica que dificultou o reconhecimento endonasal do óstio do seio frontal, ocorrendo em 45 (76,27%) fossas nasais, seguido pela bolha etmoidal (16,95%) e a célula agger nasi (6,78%).