An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice / 神经科学通报·英文版

Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex-midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.

Ultrastructural morphological alterations during hyperoxia exposure in relation to glutathione peroxidase activity and free radicals productions in the mitochondria of the cortical brain / Alteraciones morfológicas ultraestructurales durante la exposición a la hiperoxia en relación con la actividad de la glutatión peroxidasa y la producción de radicales libres en las mitocondrias de la corteza cerebral

Exposure to normobaric hyperoxia (NH) is known to increase the production of reactive oxygen species (ROS) by mitochondria. The present study was designed to examine mitochondrial ultrastructure morphological changes in the cortical brainin relation to glutathione peroxidase (GPX) activity and free radicals (FR) productions in brain tissue during hyperoxia exposure. The experimental groups were exposed to NH for 24 and 48 h continuously. Following the exposure periods, animals were sacrificed and cortical tissues were divided randomly into two parts; the first part was processed for the ultrastructural examination and the second was homogenized for GPX and FR determinations. Analysis of variance (ANOVA) showed that the main effects of O2 exposure periods were significant (p<0.05) for GPX and FR. Pair-wise means comparisons showed that NH elevated the average (+SE) GPX activity significantly (p<0.05) from the baseline control value of 5670.99+556.34 to13748.42+283.04 and 15134.19+1529.26 U/L with increasing length of NH exposure period from 24 to 48 h, respectively. Similarly, FR production was increased significantly (p<0.05) to 169.73+10.31 and 185.33+21.87, above baseline control of 105.27+5.25 Unit. Ultrastructure examination showed that O2 breathing for 48 h resulted in giant and swelled mitochondria associated with diluted inner membrane and damaged cristae. These mitochondria pathological alterations were associated with damages of myelin, axonal and cellular organelles. Normobaric-hyperoxia inducts mitochondria oxidative stress (MOS) and the subsequent rise of ROS causes variety of ultrastructure morphological pathological alterations in the organelles of cortical brain cells.

Se sabe que la exposición a la hiperoxia normobárica (HN) aumenta la producción de especies reactivas de oxígeno (ERO) por parte de las mitocondrias. El estudio se diseñó para examinar los cambios morfológicos de la ultraestructura mitocondrial en la corteza cerebral con la actividad de la glutatión peroxidasa (GPX) y la producción de radicales libres (RL) en el tejido cerebral durante la exposición a la hiperoxia. Los grupos experimentales fueron expuestos a HN durante 24 y 48 h continuamente. Tras los períodos de exposición, los animales se sacrificaron y los tejidos corticales se dividieron aleatoriamente en dos partes; la primera parte se procesó para el examen ultraestructural y la segunda se homogeneizó para las determinaciones de GPX y RL. El análisis de varianza (ANOVA) mostró que los efectos principales de los períodos de exposición al O2 fueron significativos (p <0,05) para GPX y RL. Las comparaciones de medias por pares mostraron que la HN elevó la actividad promedio de GPX (+ SE) significativamente (p <0,05) desde el valor de control de línea base de 5670,99 + 556,34 a 13748,42 + 283,04 y 15134,19 + 1529,26 U / L con una mayor duración del período de exposición a HN de 24 a 48 h, respectivamente. De manera similar, la producción de RL se incrementó significativamente (p <0,05) a 169,73 + 10,31 y 185,33 + 21,87, por encima del control de referencia de 105,27 + 5,25 unidades. El examen de la ultraestructura mostró que la respiración de O2 durante 48 h dio lugar a mitocondrias gigantes e hinchadas asociadas con la membrana interna diluida y las crestas dañadas. Estas alteraciones patológicas de las mitocondrias se asociaron con daños de mielina, axones y organelos celulares. La hiperoxia normobárica induce el estrés oxidativo mitocondrial (MOS) y el posterior aumento de las ERO provoca una variedad de alteraciones patológicas y morfológicas en los organelos de las células cerebrales corticales.

Cognitive dysfunction in corticobasal degeneration / Disfunção cognitiva na degeneração corticobasal

ABSTRACT Corticobasal degeneration (CBD) was originally described as a distinct clinicopathological entity in 1967. Since then, different phenotypic presentations have emerged as possible manifestations of CBD histopathological findings. In addition, pathophysiological findings and the molecular basis have been delineated and several aspects of its cognitive manifestations have been clarified. Thus, not only the spectrum of what is currently designated as CBD has expanded, but overlap with other degenerative and even secondary disorders has made clinical diagnostic certainty even more challenging in the absence of specific and readily-available markers. Cognitive deficits in CBD are now recognized as a frequent initial presentation and may appear up to eight years before the motor symptoms, depending on the phenotypic variant. Characteristic cognitive features of CBD involve language deficits, visuospatial and executive dysfunctions, apraxia, and behavioral disorders. Semantic and episodic memories are usually preserved, while language is often impaired in the early stages.

RESUMO A degeneração corticobasal (DCB) foi originalmente descrita como uma entidade clínico-patológica distinta em 1967. Desde então, nossa compreensão sobre DCB evoluiu substancialmente. Diferentes apresentações fenotípicas emergiram refletindo possíveis manifestações das anormalidades histopatológicos da DCB. Adicionalmente, dados fisiopatológicos e moleculares foram delineados e aspectos das manifestações cognitivas foram explorados. Assim, não só o espectro do que é atualmente designado DCB foi expandido, mas a sobreposição com outras doenças degenerativas e até mesmo secundárias tornaram o diagnóstico clínico ainda mais desafiador na ausência de marcadores específicos e prontamente disponíveis. Déficits cognitivos na DCB são agora reconhecidos frequentemente como apresentações iniciais e podem surgir até 8 anos antes dos sintomas motores, dependendo da variante fenotípica. O quadro cognitivo envolve característicamente déficits de linguagem, disfunção visuoespacial e executiva, apraxia, e distúrbios comportamentais. Anormalidades da linguagem são frequentemente descritas nos estágios iniciais da DCB.

Hallazgos morfométricos y funcionales acerca de la ínsula en población VIH+ con apatía / Morphometric and functional findings about the insula in HIV+ population with apathy

La corteza insular es uno de los componentes de la zona paralímbica que presenta conexiones con áreas corticales y subcorticales. El estudio en personas viviendo con VIH (PVVIH), donde la apatía es frecuente, la implicó como modulador de respuesta emocional y ejecutiva. El objetivo es describir morfométricamente y funcionalmente la ínsula en relación con estructuras cerebrales corticales y subcorticales en PVVIH con apatía en comparación con controles y con PVVIH sin apatía, a fin de determinar su implicancia. Estudiamos 23 encéfalos de PVVIH de sexo masculino con apatía según evaluaciones neuropsiquiátricas. Se utilizó resonancia magnética (RM) con protocolo cognitivo para cuantificación y tomografía por emisión de fotón único (SPECT) para evaluar la perfusión cortical, aplicados a: cortezas frontales, insulares, núcleos caudados y cuerpos amigdalinos. Registramos reducción significativa morfométrica de la corteza del cíngulo anterior izquierdo, núcleo caudado ipsilateral y cortezas dorso-laterales en VIH+ con apatía; la ínsula anterior registró una reducción no significativa (p=0,4). En el análisis funcional se determinó hipoperfusión en las cortezas del cíngulo anterior izquierdo, insular anterior izquierda y en el caudado de forma asimétrica; con hipoperfusiones relativas en regiones del hemisferio derecho. La perfusión de la ínsula anterior izquierda fue correlativa con la del caudado ipsilateral y proporcional a la severidad en el test de apatía. Concluimos que en la cohorte evaluada de pacientes viviendo con VIH y apatía hallamos un significativo compromiso funcional de la corteza insular anterior, correlativo con la afectación funcional y morfométrica de los núcleos caudados. La implicancia de la corteza insular sugiere su participación en la psicopatología de la apatía, parámetro vinculado con el déficit de interés por las actividades e iniciativas.

The insular cortex is one of the components of the paralimbic zone that has connections with cortical and subcortical areas. The study in people living with HIV (PLHIV), in which apathy is frequent, implicated the structure as a modulator of emotional and executive responses. The objective is to make a description based on morphometry and functionality of the insula in relation to cortical and subcortical structures in PLHIV with apathy compared to controls and compared to PLHIV without apathy, in order to determine its implication. We studied 23 brains of male PLHIV with apathy according to neuropsychiatric evaluations. Magnetic resonance imaging (MRI) with cognitive quantification protocol and Single photon emission tomography (SPECT) to evaluate cortical perfusion were used applied to: frontal cortices, insular cortex, caudate nuclei and amygdaloid bodies. We recorded a significant morphometric reduction of the left anterior cingulate cortex, left caudate nucleus and dorso-lateral cortex in PLHIV with apathy; anterior insula cortex recorded a non-significant reduction (p = 0.4). Functional analysis showed hypoperfusion in the left anterior cingulum cortex, left anterior insular region and caudate nucleus´s perfusion were assymetrically; relative hypoperfusion were found in right hemisphere regions. The perfusion of the left anterior insula was correlated with ipsilateral caudate and proportional to the severity in the apathy test. We concluded in the cohort evaluated patients living with HIV and apathy found a significant functional compromise of the anterior insular cortex, correlated with morphometric and functional impairment of the caudate nuclei. The implication of the insular cortex suggests their participation in the psychopathology of apathy, parameter linked with the deficit of interest in the activities and initiatives.

The Role of CBS in Injury Time Estimation after Brain Contusion / 法医学杂志

OBJECTIVES@#To observe the changes of cystathionine β-synthase （CBS） expression in the cerebral cortex after brain contusion at different times.@*METHODS@#An experimental model of traumatic brain injury （TBI） in mice was established by an improved weight-drop device. Then Western blotting and immunohistochemical examination were used to detect the CBS expression in cerebral cortex around injury at different time points （1 h, 6 h, 12 h, 1 d, 2 d, 3 d, 7 d）.@*RESULTS@#The results of Western blotting revealed that the expression level of CBS was down-regulated and reached its lowest level at the 3rd days after injury, and then restored to normal level after 7 days. The results of immunohistochemistry showed that CBS was present in the normal brain cortex. CBS expression gradually decreased at the 3rd days after injury, and then restored to normal level after 7 days.@*CONCLUSIONS@#CBS has the potential to be a reference index for time estimation after brain contusion in forensic practice.

Differential effect of the route of inoculation of rabies virus on NeuN immunoreactivity in the cerebral cortex of mice / Efecto diferencial de la vía de inoculación del virus de la rabia sobre la inmunorreactividad de NeuN en la corteza cerebral de ratones

Rabies is a lethal disease caused by a neurotropic virus that produces inconspicuous morphological changes hardly observable with conventional histopathology. The fatal outcome caused by rabies could be attributed to specific biochemical changes that severely impact neuronal function. The neuronal nuclear protein (NeuN) has become a widely used neuronal marker for the research and the histopathological diagnosis of nervous system diseases. To evaluate the distribution of the protein NeuN in the motor cortex of normal and rabies-infected mice adult ICR mice were inoculated with rabies virus either intramuscularly or intracerebrally. Rabies-infected mice were sacrificed at the terminal stage of the disease. Control mice were also euthanized at the same age. The brains were removed and cut into coronal sections on a vibratome. Immunohistochemistry was used to study the expression of NeuN in the motor area of the cerebral cortex. Neuronal counts, cellular optical densitometry and neuronal diameter measurements were performed to analyze the immunoreactivity of the protein. All parameters revealed decreased immunoreactivity for NeuN in cortical neurons of mice intracerebrally infected with rabies. In contrast, the changes were not statistically significant in mice inoculated intramuscularly. Either the immunoreactivity of NeuN or its expression is affected by the presence of rabies virus in the cerebral cortex depending on the inoculation route. These results contribute to the knowledge of the dynamics of cellular infection on rabies pathogenesis.

La rabia es una enfermedad mortal causada por un virus neurotrópico que produce discretos cambios morfológicos difícilmente observables con la histopatología convencional. El desenlace fatal causado por la rabia puede atribuirse a cambios bioquímicos específicos que afectan gravemente la función neuronal. La proteína nuclear neuronal (NeuN) es un marcador ampliamente utilizado para la investigación y el diagnóstico histopatológico de enfermedades del sistema nervioso. Este trabajo se realizó con el propósito de evaluar la distribución de la proteína NeuN en la corteza motora de ratones normales y ratones infectados con virus de la rabia. Ratones ICR adultos fueron inoculados con virus de la rabia por vía intramuscular o por vía intracerebral. Los animales infectados con rabia fueron sacrificados en la etapa terminal de la enfermedad. Ratones de la misma edad no inoculados con el virus (controles) fueron sacrificados simultáneamente. Se extrajeron los cerebros y se obtuvieron cortes coronales en un vibrátomo. Mediante inmunohistoquímica se estudió la expresión de NeuN en el área motora de la corteza cerebral. Se realizaron conteos neuronales, densitometría óptica celular y mediciones del diámetro de los perfiles neuronales para analizar la inmunorreactividad de la proteína. En los ratones inoculados por vía intracerebral hubo disminución significativa de la inmunorreactividad de NeuN manifestada en los diferentes parámetros evaluados. En contraste, estos cambios no fueron estadísticamente significativos en los cerebros de ratones inoculados por la ruta intramuscular. La inmunorreactividad de NeuN o su expresión es afectada por la presencia del virus de la rabia en la corteza cerebral pero dependiendo de la vía de inoculación. Estos resultados contribuyen al conocimiento de las dinámicas de infección celular en la patogénesis de la rabia.

Beneficial effects of glucan against cisplatin side effects on the nervous system in rats 1

ABSTRACT PURPOSE: To investigate the protective effect of Bg on cisplatin (CP)-induced neurotoxicity in rats. METHODS: Twenty eight rats were randomly distributed into four groups. The first group was kept as a control. In the second group, CP was given at the single dose of 7 mg/kg intraperitoneally. In the third group, βg was orally administered at the dose of 50 mg/kg/day for 14 days. In the fourth group, CP and βg were given together at the same doses. RESULTS: CP treatment caused significant oxidative damage via induction of lipid peroxidation and reductions antioxidant defense system potency in the brain tissue. In addition, histopathological damage increased with CP treatment. On the other hand, βg treatment largely prevented oxidative and histopathological negative effects of CP. CONCLUSIONS: Cisplatin has severe neurotoxic effects in rats and βg supplementation has significant beneficial effects against CP toxicity depending on its antioxidant properties. Thus, it appears that βg might be useful against CP toxicity in patients with cancer in terms of nervous system.

Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage

The timing and mechanisms of protection by hyperbaric oxygenation (HBO) in hypoxic-ischemic brain damage (HIBD) have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders) were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI) and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm) occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.

Relationship between the Expression of α-syn and Neuronal Apoptosis in Brain Cortex of Acute Alcoholism Rats / 法医学杂志

OBJECTIVES@#To observe the changes of expression of α-synuclein （α-syn） and neuronal apoptosis in brain cortex of acute alcoholism rats and to explore the mechanism of the damage caused by ethanol to the neurons.@*METHODS@#The model of acute alcoholism rat was established by 50% alcohol gavage. The α-syn and caspase-3 were detected by immunohistochemical staining and imaging analysis at 1 h, 3 h, 6 h and 12 h after acute alcoholism. The number of positive cell and mean of optical density were detected and the trend change was analyzed. The variance analysis and t-test were also performed.@*RESULTS@#The number of α-syn positive cell and average optical density in brain cortex of acute alcoholism rat increased significantly and peaked at 6 hour with a following slight decrease at 12 h, but still higher than the groups at 1 h and 3 h. Within 12 hours after poisoning, the number of caspase-3 positive cell and average optical density in brain cortex of rats gradually increased.@*CONCLUSIONS@#The abnormal aggregation of α-syn caused by brain edema and hypoxia may participate the early stage of neuronal apoptosis in brain cortex after acute alcoholism.

Degeneración corticobasal: reporte de un caso / Corticobasal degeneration: a case report

Se presenta un caso de Degeneración Corticobasal en una paciente chilena de 48 años de edad. La evolución clínica fue progresiva, con parkinsonismo (rigidez, acinesia, alteraciones posturales, disartria), deterioro cognitivo, apraxia del vestir, apraxia constructiva e hipomimia. Además, la paciente presentaba afasia no fluente. Adicionalmente, fue diagnosticada con Síndrome Depresivo Crónico (SDC) y Trombosis Venosa Profunda (TVP) de la extremidad inferior izquierda. Se han descrito varios tipos de enfermedades neurodegenerativas en las últimas décadas, las cuales cumplen con distintas características patológicas y clínicas. Sin embargo, la diferenciación de estas, en la práctica, es compleja y se necesita de una apreciación clínica entrenada, evaluaciones clínicas detalladas, neuroimágenes y estudios de laboratorio para lograr llegar a un diagnóstico adecuado. Dentro de las principales enfermedades neurodegenerativas que se presentan con parkinsonismo encontramos las llamadas “taupatías”, que son la Degeneración Corticobasal (DCB) y la Parálisis Supranuclear Progresiva*(PSP)...

A case study of corticobasal degeneration in a Chilean 48 year old female patient is reported. The clinical course was progressive and included Parkinsonism (rigidity, akinesia, postural abnormalities, dysarthria), cognitive impairment, dressing apraxia, constructive apraxia and hypomimia. In addition, the patienth ad non Mfluent aphasia. Also, the patient was diagnosed with Chronic Depressive Syndrome and Deep Venous Thrombosis (DVT) of the left lower extremity. In recent decades, several types of neurodegenerative diseases* have been described. These diseases have different clinical and pathologic features. However, in practice, it is difficult to differentiate them from one another and, to reach an accurate diagnosis, advanced medical skills, detailed clinical evaluations of neuroimaging and laboratory studies are needed. “Tauopathies”, which are Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP) are among the major neurodegenerative diseases occurring with Parkinsonism...

Alterations of the giant pyramidal neurons (Betz cells) in brain cortex of rat offspring born from gestational diabetic dams: a morphometric study / Alteraciones de las neuronas piramidales gigantes de la corteza cerebral en crías de ratas nacidas de hembras con diabetes gestacional: un estudio morfométrico

A few studies reported the adverse effects of gestational diabetes on hippocampus and spinal cord of rat offspring. Giant pyramidal neurons are giant pyramidal neurons located in fifth layers of the gray matter in the primary motor cortex. Therefore, this study was conducted to determine the effect of gestational diabetes on the giant pyramidal neurons and the thickness of internal pyramidal layer in the brain cortex of rat offspring. On day 1 of gestation, 10 Wistar rat dams were randomly allocated into two control and diabetic groups. Five animals in diabetic group received 40 mg/kg/BW of Streptozotocin (intraperitoneally) and control animals received normal saline. We randomly selected six offspring of every subject in both groups at day 28, 56 and 84. Rat offspring were scarified and then coronal sections were taken from the right brain cortex and sections were stained with Cresyl violet. The density of giant pyramidal neurons in brain cortex and thickness of internal pyramidal layer of brain cortex were evaluated. In P28, P56, P84 the Betz cells density of brain cortex were significantly reduced from 107.6±6.2, 131.6±4.6 and 143.5±4.0 in controls to 84.96±2.1, 109.8±7.3 and 121.05±5.6 in cases (p<0.05), respectively. The thickness of the internal pyramidal layer of brain cortex in P28, 56 and P84 was significantly higher in gestational diabetic group in comparison with the control group (p<0.05). This study showed that uncontrolled gestational diabetes reduces the giant pyramidal neurons density and internal pyramidal layer thickness in brain cortex of rat offspring.

Pocos estudios han informado de los efectos adversos de la diabetes gestacional sobre las células del hipocampo y médula espinal. Este estudio, se realizó para determinar el efecto de la diabetes gestacional sobre las neuronas piramidales gigantes ubicadas en la quinta capas de la sustancia gris en la corteza motora primaria y el espesor de la capa piramidal interna en la corteza cerebral en crías de ratas. En el día 1 de la gestación, 10 ratas Wistar se asignaron aleatoriamente en dos grupos: control y diabéticos. Cinco animales del grupo diabético, fueron inyectados con 40 mg/kg de peso corporal de estreptozotocina (por vía intraperitoneal), y los de el grupo control, con solución salina. Aleatoriamente, se seleccionaron seis crías de cada hembra de ambos grupos los días 28, 56 y 84. Las crías fueron sacrificadas, se tomaron secciones coronales de la corteza cerebral derecha y se tiñeron con violeta de cresilo. Se evaluó la densidad de las neuronas piramidales gigantes en la corteza cerebral y el espesor de la capa piramidal interna de la corteza cerebral. En los días 28, 56, 84 la densidad de las neuronas piramidales gigantes en corteza cerebral se redujo significativamente al comparar los controles (107,6±6,2, 131,6±4,6 y 143,5±4,0 respectivamente) con los casos (84,96±2,1, 109,8±7,3 y 121,05±5,6 respectivamente) (p<0,05). El espesor de la capa piramidal interna de la corteza cerebral en los días 28, 84 y 56 fue significativamente mayor en el grupo diabético gestacional en comparación con el grupo control (p<0,05). Este estudio muestra que la diabetes gestacional no controlada reduce la densidad de neuronas piramidales gigantesy el espesor interno de la capa piramidal en la corteza cerebral de las crías de rata.

Cortical correlates of affective syndrome in dementia due to Alzheimer’s disease / Correlatos corticais da síndrome afetiva na demência da doença de Alzheimer

Neuropsychiatric symptoms in Alzheimer’s disease (AD) are prevalent, however their relationship with patterns of cortical atrophy is not fully known. Objectives To compare cortical atrophy’s patterns between AD patients and healthy controls; to verify correlations between neuropsychiatric syndromes and cortical atrophy. Method 33 AD patients were examined by Neuropsychiatric Inventory (NPI). Patients and 29 controls underwent a 3T MRI scanning. We considered four NPI syndromes: affective, apathy, hyperactivity and psychosis. Correlations between structural imaging and neuropsychiatric scores were performed by Freesurfer. Results were significant with a p-value < 0.05, corrected for multiple comparisons. Results Patients exhibited atrophy in entorhinal cortices, left inferior and middle temporal gyri, and precuneus bilaterally. There was correlation between affective syndrome and cortical thickness in right frontal structures, insula and temporal pole. Conclusion Cortical thickness measures revealed atrophy in mild AD. Depression and anxiety symptoms were associated with atrophy of right frontal, temporal and insular cortices. .

Os sintomas neuropsiquiátricos na doença de Alzheimer (DA) são prevalentes, porém suas relações com padrões de atrofia cortical não são totalmente compreendidas. Objetivos Comparar padrões de atrofia cortical entre DA e controles; verificar se há correlações entre sintomas neuropsiquiátricos e atrofia cortical. Método 33 pacientes com DA foram examinados pelo Inventário Neuropsiquiátrico. Os pacientes e 29 controles foram submetidos à RNM. Consideramos quatro síndromes: afetiva, apatia, hiperatividade e psicose. Correlações entre imagens estruturais e os scores foram feitas pelo Freesurfer. Os resultados foram significantes com um valor de p < 0,05, corrigido para múltiplas comparações. Resultados Pacientes exibiram atrofia nos córtices entorrinais, giros temporal médio e inferior esquerdos, e precuneo bilateralmente. Houve correlação entre síndrome afetiva e espessura cortical em estruturais frontais direitas, ínsula e polo temporal. Conclusão Medidas de espessura cortical revelaram atrofia na DA. Sintomas de depressão e ansiedade foram associados à atrofia dos córtices frontal direito, temporal e ínsula. .

Fundamentals of Brain Tumor Surgery in Eloquent Areas / Fundamentos da cirurgia de tumor cerebral em áreas eloquentes

Central nervous system tumors are a major cause of morbidity and mortality. Themain pathology involved is brainmetastases, followed by intrinsic gliomas. In nearly all cases, surgery is the initial and most important measure to change natural course of disease. In brain metastases and meningiomas, gross total resection is also precluded, and usually more achievable, because of biological behavior of tumor and extrinsic presentation. Generally these tumors push or compress eloquent areas, but spare them. In intrinsic tumors, complete resection is often difficult, once tumor is invasive and may even be within eloquent cortex.When tumors occur in eloquent areas such as sensorial, motor and language cortex, there is the need for taking several measures to avoid worsening of symptoms after surgery. Especially in lesions involving language cortex, an awake craniotomy may be performed to assess intraoperatively language functions.(AU)

Tumores no Sistema nervoso central são a maior causa de morbimortalidade. A principal patologia é metástase do cérebro, seguida de gliomas intrínsecos. Em quase todos os casos, cirurgia é a primeira e mais importante medida para impedir a evolução da doença. Em metástase do cérebro e meningiomas, ressecção brutal total é igualmente excluída e geralmente mais factível, devido ao comportamento biológico do tumor e apresentação extrínseca. Normalmente, estes tumores empurram ou comprimem áreas eloquentes, mas o separam. Em tumores intrínsecos, a ressecção completa é difícil, uma vez que o tumor é invasivo e pode até mesmo estar dentro córtex. Quando tumores ocorrem em áreas eloquentes, como a sensorial, a motora e o córtex de linguagem, há a necessidade de tomar diversas medidas para evitar piora dos sintomas pós-cirúrgicos. Particularmente em lesões envolvendo o córtex da linguagem, uma craniotomia desperta deve ser realizada para acesso funções linguísticas de forma intraoperativa.(AU)

Immunohistochemical overexpression of MAP-2 in the cerebral cortex of rabies-infected mice / Aumento en la expresión inmunohistoquímica de MAP-2 en la corteza cerebral de ratones infectados con rabia

The microtubule-associated protein MAP-2 is an integral part of the cytoskeleton and plays an important role in neural morphogenesis. This protein is an essential component of the dendritic cytoskeleton, especially in the adult brain, and its expression can be altered under experimental or pathological conditions. The purpose of this study was to evaluate the effect of infection with the rabies virus on MAP-2 immunoreactivity in the cerebral cortex of mice. The mice were inoculated with the rabies virus and the animals were sacrificed when the disease reached its advanced stage, together with uninfected animals of the same age. The brains were extracted after being previously perfusion-fixed with paraformaldehyde; coronal sections were obtained with a vibratome. The coronal sections were processed by immunohistochemistry to reveal the presence of the MAP-2 protein in neurons of the motor area of the cerebral cortex. Rabies-infected mice showed an increase in the immunoreactivity of the somata and apical dendrites in pyramidal neurons of the motor cortex. This is an unexpected result, as dendritic pathology has been previously demonstrated in rabies, and some studies on neurological disorders associate dendritic alterations with loss of expression of the MAP-2 protein. Therefore, whatever the alteration in the expression of this protein, decrease or increase, it could be causing a biochemical imbalance in the integrity and stability of the neuronal cytoskeleton.

La proteína asociada a microtúbulos MAP-2 es una parte integral del citoesqueleto y juega un papel importante en la morfogénesis neuronal. Esta proteína es un componente esencial del citoesqueleto de las dendritas, especialmente en el cerebro adulto, y su expresión puede ser alterada en condiciones experimentales o patológicas. El propósito de este estudio fue evaluar el efecto de la infección con el virus de la rabia sobre la inmunorreactividad de MAP-2 en la corteza cerebral de ratones. Ratones inoculados con el virus de la rabia fueron sacrificados cuando la enfermedad alcanzó su fase avanzada, junto con animales no infectados de la misma edad. Los cerebros se extrajeron después de que los animales fueron tratados con paraformaldehído mediante perfusión intracardiaca. En un vibrátomo se obtuvieron cortes coronales y estos se procesaron mediante inmunohistoquímica para revelar la presencia de la proteína MAP-2 en las neuronas de la zona motora de la corteza cerebral. Los ratones infectados con rabia mostraron un aumento en la inmunorreactividad de los somas y dendritas apicales en las neuronas piramidales de la corteza motora. Este es un resultado inesperado, ya que previamente se ha demostrado patología dendrítica en rabia, y algunos estudios sobre los trastornos neurológicos asocian las alteraciones dendríticas con pérdida de expresión de la proteína MAP-2. Por lo tanto, cualquiera que sea la alteración en la expresión de esta proteína, disminución o aumento, podría ser la causa de un desequilibrio bioquímico en la integridad y estabilidad del citoesqueleto neuronal.

Histological study of the cerebral cortex and spinal cord in a model of experimentally induced autoimmune encephalomyelitis in adult albino rabbits

Axonal damage is responsible for the increasing disability seen in patients afflicted with multiple sclerosis [MS]. An animal model of autoimmune encephalomyelitis may help to develop better therapeutic and neuroprotective strategies. The aim of the study was to investigate the histological patterns of axonal injury and the mechanism of demyelination in autoimmune encephalomyelitis in the cerebral cortex and spinal cord of adult albino rabbits. Twenty male adult albino rabbits were divided into two groups: the control group - group I [10 animals] - and the experimental group - group II [10 animals]. Autoimmune encephalomyelitis was induced by the injection of 0.3 ml/kg of 0.01% ethidium bromide solution. The animals were sacrificed and their cerebral cortex and spinal cord were processed for light microscopic examination, whereas electron microscopy was used to study the lumbar segment of spinal cord. Light microscopic examination of the cerebral cortex and spinal cord showed some cellular infiltration, together with degeneration and necrosis of nerve cells. Electron microscopic examination of the white matter of the spinal cord showed areas of destruction of nerve fibers, together with defective myelination. The extent of motor neuron inflammation and demyelination, axonal damage, and white matter pathology are reflective of the severity of experimental MS. Our results delineate the experimental autoimmune encephalomyelitis model as a valuable tool for MS research

0.1T magnetic resonance image in the study of experimental hydrocephalus in rats. Accuracy of the method in the measurements of the ventricular size / Imagem de ressonância magnética de 1,0T no estudo da hidrocefalia experimental em ratos. Avaliação do método de medição do tamanho ventricular

PURPOSE: To investigate the accuracy of 1.0T Magnetic Resonance Imaging (MRI) to measure the ventricular size in experimental hydrocephalus in pup rats. METHODS: Wistar rats were subjected to hydrocephalus by intracisternal injection of 20% kaolin (n=13). Ten rats remained uninjected to be used as controls. At the endpoint of experiment animals were submitted to MRI of brain and killed. The ventricular size was assessed using three measures: ventricular ratio (VR), the cortical thickness (Cx) and the ventricles area (VA), performed on photographs of anatomical sections and MRI. RESULTS: The images obtained through MR present enough quality to show the lateral ventricular cavities but not to demonstrate the difference between the cortex and the white matter, as well as the details of the deep structures of the brain. There were no statistically differences between the measures on anatomical sections and MRI of VR and Cx (p=0.9946 and p=0.5992, respectively). There was difference between VA measured on anatomical sections and MRI (p<0.0001). CONCLUSION: The parameters obtained through 1.0T MRI were sufficient in quality to individualize the ventricular cavities and the cerebral cortex, and to calculate the ventricular ratio in hydrocephalus rats when compared to their respective anatomic slice.

OBJETIVO: Investigar a fidelidade das Imagens de Ressonância Magnética de 1,0T no estudo do tamanho ventricular na hidrocefalia experimental em ratos jovens. MÉTODOS: Ratos Wistar foram submetidos à hidrocefalia através da injeção intracisternal de caulim 20%. Dez animais permaneceram sem injeção para uso como controles. Ao final do experimento, os animais foram submetidos à Ressonância magnética de encéfalo e sacrificados. O tamanho ventricular foi avaliado por três medidas: razão ventricular (VR), espessura cortical (Cx) e área ventricular (VA), tomadas em fotografias das secções anatômicas e nas imagens de ressonância magnética (RM). RESULTADOS: As imagens por RM apresentaram qualidade suficiente para individualizar os ventriculos laterais, mas a distinção entre córtex e substância branca, bem como detalhamento das estruturas profundas do encéfalo não foram possíveis. Quando comparadas as medidas em seções anatômicas e RM, não houve diferença estatística entre as médias de razão ventricular e espessura cortical (p=0,9946 e p=0,5992, respectivamente). Houve diferença da área ventricular comparando-se as secções anatômicas e ressonância magnética (p<0,0001). CONCLUSÃO: Os parâmetros obtidos através de imagens da ressonância magnética de 1,0T foram suficientes para individualizar as cavidades ventriculares e o córtex cerebral, e para calcular o tamanho ventricular em ratos hidrocefálicos quando comparados aos seus respectivos cortes anatômicos.

Estatus parcial continuo, causa de hiperintensidad de la corteza cerebral en la resonancia nuclear magnética / Continous partial status cause of hyperintensity in cerebral cortex in magnetic resonance imaging

Magnetic Resonance Imaging has demonstrated functional changes of the cerebral cortex in relation to status epilepticus, which can eventually localize the origin of the crisis. The purpose of this presentation is relevant to this condition and pretends to highlight the action of incidental situations that can modify it. We present a 29 year old woman with a neurosurgical intervention for a neuroblastoma irradiated fifteen years ago, which incidentally starts a continuous partial status epilepticus, expressed by clonies of the face and left limbs associated with functional impotence, resistant to oral therapy. Faced with the suspicion of recurrence of the tumor, a brain MRI is performed, showing hyperintensity of all neural areas the right hemisphere, with no evidence of tumor recurrence. Once submitted the status epilepticus, the hyperintensity disappeared in the hemisphere. This extensive reaction of the neural structures might be related to a permanent effect of radiation, which may have caused a mismatch functional glia, of the blood-brain barrier and interneural network.

La Resonancia Nuclear Magnética (RM) ha puesto en evidencia cambios funcionales de la corteza cerebral en relación a estados epilépticos que eventualmente permiten localizar el origen de las crisis. El propósito de esta presentación es hacer relevante dicha condición y destacar la acción de situaciones incidentales que pueden modificarla. Se presenta a una mujer de 29 años portadora de una intervención neuroquirúrgica por un neuroblastoma irradiado hace quince años, que incidentalmente inicia un estatus epiléptico parcial continuo, expresado por clonías de la cara y extremidades izquierdas asociadas a impotencia funcional resistente a la terapia oral. Frente a la sospecha de recidiva de la neoplasia se realiza RM cerebral que muestra una hiperintensidad de todas las áreas neuronales del hemisferio derecho, sin evidencias de recidiva tumoral. Una vez remitido el estado epiléptico se observó una desaparición de estas alteraciones. La interpretación para esta extensa reacción de las estructuras neurales podría estar relacionado con un efecto permanente de la irradiación, que pudo haber provocado un desajuste funcional de la glía, de la barrera hematoencefálica y de la red interneural.

Encefalopatía hepática fulminante vinculada a hiperintensidad de la corteza cerebral en la resonancia magnética / Fulminant hepatic encephalopathy vinculated with hyperintensity of the cerebral cortex in magnetic resonance

Background: The presence of manganese deposits in basal ganglia is an expression of chronic liver damage in neuroimaging, whereas diffuse edema of the white matter and hyperintensity of the internal capsule are seen in MRI in acute decompensation. In fulminant encephalopathy, changes in intensity in the cerebral cortex have been described, suggesting different pathogenic aspects. Purpose: To describe and try to interpret hyperintensities images of the cerebral cortex in fulminant hepatic encephalopathy. Case report: A 42 years old woman, with history of hyperthyroidism treated with propylthiouracil developed abdominal pain, choluria and general malaise, without fever. At admission, she had jaundice, elevated liver enzymes, and hyperammronemia of 481 ug. She developed progressive impairment of consciousness falling into a non-reactive coma with intermediate size and poorly reactive pupils, absence of oculocephalic reflexes and diminished osteotendinous reflexes, with indifferent plantar reflexes. Brain CT showed brain edema without focal lesions. The MRI showed hyperintense signal abnormalities in the fronto-parietal cortex in T2 and FLAIR with restriction in difussion sequency. She became brain dead. Comment: These exceptional images on MRI are considered an expression of cytotoxic damage, consistent with high levels of ammonium in fulminant hepatic encephalopathy. The swelling of astrocytes and cortical neurons is caused by the accumulation of intracellular glutamine, highly osmophilic, and explains the restriction on the difussion and lower values in the ADC. Interstitial edema would be part of the chronic forms by acquisition of compensatory mechanisms capable of preventing the accumulation of glutamine.

Antecedentes: La presencia de depósitos de manganeso en los núcleos basales es una expresión neuroimagenológica de daño hepático crónico, así como el edema difuso de la substancia blanca y la hiperintensidad de la cápsula interna con RM en descompensaciones agudas. En encefalopatías fulminantes se ha visualizado cambio de intensidad en la corteza cerebral, sugiriendo aspectos patogénicos distintos. Propósito: Describir e intentar interpretar imágenes hiperintensas de la corteza cerebral en una encefalopatía hepática fulminante. Caso clínico: Mujer de 42 años, hipertiroidea en tratamiento con propiltiouracilo. Consultó por dolor abdominal, coluria y compromiso del estado general, sin fiebre. Ingresó con ictericia, enzimas hepática elevadas, e hiperamonemia de 481 ug. Desarrolló progresivo compromiso de conciencia cayendo en un coma no reactivo, con pupilas de tamaño intermedio pobremente reactivas, ausencia de reflejos oculocefálicos y reflejos osteotendíneos apagados, con reflejos plantares indiferentes. TAC de cerebro mostró edema cerebral, sin lesiones focales. La RM definió áreas hiperintensas en la corteza fronto-parietal en T2 y FLAIR, que presentaban incremento de señal en la difusión. Evolucionó hasta la muerte cerebral. Comentario: Estas imágenes excepcionales en la RMson consideradas expresión de daño citotóxico, en concordancia con los altos niveles de amonio de una encefalopatía hepática fulminante. El edema de astrocitos y neuronas corticales se origina por la acumulación de glutamina intracelular, altamente osmofílica, y explica la restricción en la difusión y valores menores en el ADC. El edema intersticial, sería atributo de las formas crónicas, debido a la adquisición de mecanismos compensatorios capaces de impedir la acumulación de glutaminas.