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.

Impact of dexmedetomidine on amino acid contents and the cerebral ultrastructure of rats with cerebral ischemia-reperfusion injury

Abstract Purpose: To investigate the effects of dexmedetomidine (DEX) on amino acid contents and the cerebral ultrastructure of rats with cerebral ischemia-reperfusion injury (I/R). Methods: Thirty-six, male, Wistar rats were randomly divided into three groups: the sham operation group (group C), the ischemia-reperfusion group (group I/R), and the DEX group (group D). The middle cerebral artery occlusion model was prepared by the modified Longa method. The time of ischemia was 180 min, and 120 min after reperfusion, the amount of glutamate (Glu), and γ-aminobutyric acid (GABA) in the brain were measured, and the ultrastructure-level changes in the cerebral cortex were examined using electron microscopy. Results: Compared to group C, Glu contents in group D, and I/R significantly increased. Compared to group I/R, Glu contents in group D significantly decreased. Compared to group C, GABA contents in group D, and I/R significantly increased, and those in group D significantly increased, as compared to group I/R. The cerebral ultrastructure was normal in group C. Vacuolar degeneration in the plastiosome and nervous processes, was more critical than in group D. Vascular endothelial cells (VEC) were damaged. On the contrary, these changes in group D significantly improved. Conclusion: Dexmedetomidine is capable of decreasing glutamergic content, and increasing GABAergic content, in order to decrease the injury of the cerebral ultrastructure, following cerebral ischemia-reperfusion injury.

possible ameliorating effect of Nigella sativa oil on tramadol induced apoptosis in the motor area of rat cerebral cortex: a histological and immunohistochemical study

Tramadol is a centrally active analgesic commonly prescribed for moderate to severe pain. Thymoquinone, the major active component of the Nigella sativa oil, is characterized by its antioxidant properties. This study aimed to demonstrate the histological and p53-immunohistochemical changes induced by tramadol in the rat cerebral cortex and evaluate the potential role of N. sativa oil in the attenuation of these changes. Twenty-four male albino rats divided into three groups were used in this study. Group I was the control group. Group II was given repeated intraperitoneal injections of increasing doses of tramadol of 20, 40, and 80 mg/kg/day on the first, second, and third ten days of the study, respectively. Group III was given oral N. sativa oil 4 ml/kg/day, 30 min before each tramadol injection for 30 days. Paraffin sections of the frontal cortex motor area were prepared and stained with H and E and with an immunohistochemical stain using anti-p53 antibody. In group II rats, numerous shrunken pyramidal cells with acidophilic cytoplasm and deeply stained pyknotic nuclei were seen. Some of the granular cells appeared as ghosts with margination of chromatin. Homogeneous acidophilic masses containing fragmented deeply stained nuclei and surrounded by clear halos were also observed. The number of p53-positive cells was significantly higher compared with both group I and group III. In contrast, in group III, multiple pyramidal and granular cells appeared normal and the number of p53-positive cells was significantly less compared with group II. N. sativa oil and derived thymoquinone ameliorate tramadol-induced apoptosis in the motor area of the rat cerebral cortex

Harmful effects of arsenic on the cerebral cortex of adult male albino rats: light and electron microscopic studies

Arsenic is a common environmental contaminant that is available worldwide. It has been reported that human arsenic exposure causes nervous system disturbances such as polyneuropathy and neurobehavioral deficits. The purpose of this work was to describe the histological changes induced by arsenic in the cerebral cortex of adult male albino rats and discuss its possible mechanisms of action. Twenty adult male albino rats were equally classified into control [I] and experimental [II] groups of 10 animals each. Rats of group II were intraperitoneally injected with 2mg/kg/day of sodium arsenite for 20 days. Samples from the temporal lobes of the cerebrum were taken and processed for light and electron microscopic examination. Features of neurodegeneration such as shrunken, irregular, and darkly stained nuclear and degenerating organelles were observed in arsenic-treated rats. Good evidence of gliosis and disrupted blood-brain barrier were also detected. The adult brain is particularly susceptible to arsenic-induced oxidative stress and contributes to the neurodegenerative lesions

Effect of chronic lead exposure in various doses on the pyramidal cell neurons of the developing cerebral cortex in young rats [light and electron microscopic study]

Lead represents a toxin which affects the developing nervous system with neuro-behavioural deficits. The present study was planned with the aim of studying the morphological changes that might occur in the cerebrum of the young rats in response to two different doses of the lead for 3 months, and discover whether these changes are reversible or irreversible. Fifty young albino rats, aged 4-5 weeks, were used in the present work. They are classified into 3 groups: a control group [10 rats], group "A" [20 rats] received a low dose of lead acetate for 3 months, and group "B" [20 rats] received a high dose of lead acetate for 3 months. Ten rats of both groups "A" and "B" were sacrificed one month after the last given dose of lead [ie. recovery animals]. The cerebral cortex of the young rats of the group "A" showed that pyramidal cell neurons are little in number. Some of them are atrophic and other showed either degenerating mitochondria and dilated Golgi apparatus or ill-defined cytoplasmic organelles. Also, there is obvious perivascular oedema. In addition, most myelinated axons showed vacuolation of their myelin sheaths. The cerebral cortex of the young rats of the group "B" showed that most of the pyramidal cell neurons are distorted, with irregular nuclear membrane, proliferative endoplasmic reticulum, dilated Golgi apparatus and degenerating mitochondria. Also, wide-spread gliosis and extensive pericellular oedema were evident. Most myelinated axons showed vacuolation of myelin sheaths, and vacuolated or ill-defined axoplasm. The cerebral cortex of the recovery animals of the group "A" showed nearly complete recovery, while that of the group "B" showed incomplete recovery in the form of perivascular oedema and abnormal myelinated and non-myelinated axons

Histological study on the effect of pyridoxine [vitamin B6] overdose on rat cerebral cortex

Vitamin B[6] plays vital roles in numerous metabolic processes in the human body, such as nervous system development and function. High intake of this vitamin may result in intoxication. In this study, the effect of a high dose of pyridoxine on the rat cerebral cortex was investigated. Thirty six albino rats were used in this study. The animals were divided into three groups [12 animals each]; control group that received daily intraperitoneal saline injections for 3 weeks and two experimental groups received vitamin B[6] at a dose of 5mg/kg/day intraperitoneally for three weeks. One of the two experimental groups left for 3 weeks after stoppage of the drug for recovery. Specimens from the cerebral cortex were taken and examined by both light and electron microscopy. The neuronal mitochondria demonstrated swelling with loss of matrix density. In some neurons, mitochondria demonstrated homogenously increased matrix density and some appeared disrupted. There was overall decrease of neuronal cellular processes and organelles. The neuropil appeared vacuolated. The results of the present study showed that high intake of vitamin B[6] causes damage to the rat cerebral cortex. It could be concluded that the dose of vitamin B[6] should be taken into consideration during vitamin B[6] supplementation

Experimental simulation for accidental exposure to uranium pollutants in drinking water a histological study on the possible impact to the cerebral cortex of adult albino rats

The international racing between countries for using uranium element and its isotopes led to renewal of the efforts evaluating its health impacts. The present study aimed at assessing the possible histological alterations in the cerebral cortex of albino rats ingesting a soluble uranium compound as an experimental simulation to the long term exposure to uranium pollutants in drinking water. Ten control adult male albino rats have received daily 1 ml of ordinary tap water by orogastric intubation for 90 days. Another group of 15 experimental rats have received 60 micro g / kg body weight dissolved uranium in 14.21 micro ml uranyl acetate added to 1 ml tap water by the same route and for the same duration. Specimens from the left fronto-temporal area of the cerebral cortices of both groups of animals were processed for light microscopic examination by routine hematoxylin and eosin stain and immunohistochemical labeling for glial fibrillary acidic protein as well as for transmission electron microscopy. The applied dose and duration of exposure to uranyl acetate in drinking water proved to induce focal degenerative changes in some neurons of the cerebral cortex, which was associated with moderate increase in the neuroglial reaction. Regular, short-termed monitoring of uranium levels in all sources of drinking water is mandatory at the local as well as the national ranges. The population at risk for high rates of exposure should be subjected to periodic assessment of uranium level in urine. The efforts of the national and international health organizations together with the governments should be directed to limit the expanding utilization of uranium compounds in civilian and military applications

toxic effect of prolonged ultram administration on cerebral cortex of albino rats. Toxicological and histological study

Ultram [Tramadol] is a widely used opioid analgesic effective in treating both acute and chronic pains and has acceptable adverse effects. The aim of the present study was to evaluate the cerebrocortical toxicity resulting from one month and two month Ultram administration in to albino rats using biochemical and histological parameters. The study was carried out on 25 adult male albino rats divided into: control group received 0.5 ml /day saline orally by orogastric tube for two months, a short-term Ultram-treated group that received a dose of 30 mg/kg/day [1/10 LD50] for one month orally and a long-term Ultram-treated group that received the same dose for two months. The study revealed that Ultram administration caused a significant elevation of serotonin level in the cerebral cortical tissues of rats which was directly proportional to the duration of Ultram admistration. Histologically, there were many changes in the organization and ultrastructure of neurons in the different layers of cerebral cortex associated with an increased response of the supporting neuroglial cells. Intense neurological tissue lesions were more evident with the two months Ultram dosing than with one month. The correlation between the biochemical results and the histological findings proved that Ultram induced neuronal lesions could be mediated by the elevated cerebrocortical serotonin level which gives serious alarms for reconsidering the rush towards the excessive use of ultram

Effect of lead toxicity on ultrastructure of cerebral cortex of adult rat

Lead is a major air polluant in large cities including Cairo. This study was designed to evaluate the lead induced toxic effects on the cerebral cortex of adult rats. Fifteen normal adult rats were used. They were divided into 2 groups: 5 rats as a control group and the other 10 rats were subdivided into 2 subgroups. Subgroup A [5 rats] were given lead as 400 ug/g body weight / day by gastric intubation [as high dose] for 2 months. Subgroup B [5 rats] were given lead as 100 microg/g body weight /day [as low dose] for 2 months. In the rats treated with low dose of lead, gliosis was seen as an apparent degenerative feature. Also, infiltration with inflammatory cells was evident. However, in the rats treated with high dose the degenerative changes were more evident. The neurons were distended and few. Nuclear and cytoplasmic lead inclusions were detected. Other features included; indented nuclear membranes, dilated endoplasmic reticulum as well as gliosis

Effects of potassium cyanide on the cerebral cortex of albino rats: histological, histochemical and Ultrastructural study

The central nervous system [CNS] is the primary target system which is affected by cyanide toxicity. Repeated exposure to potassium cyanide causes loss of tyrosine-hydroxylase-containing neurons and locomotor dysfunction. Cyanide intoxication causes progressive degeneration of the CNS similar to neuropathology associated with Parkinson's disease and cell death in certain brain areas. The purpose of this study is to demonstrate the effect of potassium cyanide which is considered as an example of one of the three derivatives of cigarette smoking: nicotine, carbon monoxide and hydrogen cyanide. Our investigation involved 25 male albino rats. Ten of them were assigned as the control group and the remaining were injected with potassium cyanide [0.02 mg/kgm body weight every day] intraperitoneally over 4 weeks. Parts of the motor cortex of each animal were freshly cut for demonstration of acid phosphatase enzyme activity. Another part was immediately processed for routine histological examination. The last part was prepared for electron microscopic examination. Light microscopic examination of the motor cortex of cyanide treated rats revealed marked degenerative changes involving the majority of their cells. Many cells were shrunken, having irregular outline, containing many cytoplasmic vacuoles and pyknotic nuclei. Cresyl violet stained sections showed chromatolysis [in the form of marked reduction of staining of Nissl substance] in the majority of cortical neurons. Transmission electron micrographs revealed both neuronal and axonal degenerative changes in cyanide treated rats. Pyramidal cells showed irregular shape, many cytoplasmic vacuoles, corrugated cell membrane, degenerated mitochondria and condensed nuclei. In addition, the nerve fibers showed, beading appearance and irregularity of the myelin layers. Thus our results might draw more attention to the harmful effects of smoking as well as might explain fine tremors affecting head and fingers of old aged heavy smokers, concerning the cerebral cortical neuronal affection especially pyramidal cells following cyanide exposure

Desarrollo dendrítico de las células piramidales de la neocorteza en víctimas del síndrome de muerte súbita infantil / Neocortical pyramidal cell dendritic development in victims of the sudden infant death syndrome

En pacientes fallecidos por síndrome de muerte súbita infantil se han descrito alteraciones de la maduración neuronal en el tronco cerebral y gliosis. Propósito: determinar si existen alteraciones en niños fallecidos por síndrome de muerte súbita infantil. Sujetos y método: mediciones de densidad, longitud y volumen del cilindro dendrítico de las células piramidales en preparaciones de la corteza motora de cuatro lactantes fallecidos por síndrome de muerte súbita infantil y cuatro controles muertos por neumonía. Las preparaciones fueron teñidas con la técnica de Golgi-Cox y evaluados con métodos morfométricos. Resultados: no se encontraron diferencias significativas en la densidad, número de ramas dendríticas a diferentes distancias del soma neuronal y volumen del cilindro dendrítico basal entre los lactantes fallecidos por neumonía y los considerados como casos de muerte súbita infantil, pero en estos últimos se registró, a diferencia de los controles, marcado proliferación de la glia. Conclusión: en lactantes fallecidos por síndrome de muerte súbita la maduración neuronal podría no ser afectada por aquellos factores que, en cambio, inducirían un retardo de la maduración histológica de núcleos del tronco encefálico y gliosis difusa del tejido nervioso. La gliosis sugiere exposición crónica a situaciones de hipoxia

Eletroscilogramas das areas corticais do rato durante o alerta e o sono dessincronizado: topografia diferencial da dessincronizacao e das ondas teta / Cortical eletro-oscilograms during wakefulness and desynchronized sleep: differential topography of desynchronization and theta waves

No estudo do ciclo vigilia-sono de varias especies demonstra-se a ocorrencia de periodos de vigilia e sono com diferentes graus de vigilancia e de atencao. Tanto no rato como no homem e outros primatas evidenciam-se alguns periodos de intenso grau de atencao no alerta vigil e na atividade onirica (sono dessincronizado), com grande correlacao entre essas fases demonstrada por eventos fisiologicos perifericos (manifestacao motora) e caracteristicas eletroscilograficas semelhantes...

Serotonin reverses the inhibitory effect of a brain soluble fraction on synaptosomal membrane Na+, K(+)-ATPase activity

Normal operation of the Na+ pump (Na+, K(+)-ATPase) is essential for the maintenance of neurotransmission. Filtration through Sephadex G-50 of a brain soluble fraction allowed the separation of peaks I and II fractions, respectively stimulating and inhibiting synaptosomal membrane Na+, K(+)-ATPase activity. Peaks I and II were isolated from rat cerebral cortex and their effect together with serotonin (5-HT) was studied on ATPase activity by estimating K(+)-p-nitrophenylphosphatase activity in brain cortex synaptosomal membranes. It was observed that 10(-5) or 10(-4) M 5-HT failed to modify either control membrane enzyme activity or peak I activatory effect; on the other hand, such 5-HT concentrations significantly suppressed peak II inhibitory effect. This ability of 5-HT to reverse the inhibitory effect of endogenous factors on Na+, K(+)-ATPase activity could well be a new 5-HT modulatory action within the brain.

The anatomical substrates for language and hemispheric specialization

Three main lines of investigation are discussed in this paper: (1) the comparison between the anatomical arrangement of the language areas and the large-scale neurocognitive cortical networks partly involved in active or working memory; (2) the relations between hemispheric specialization and the development of interhemispheric communication; and (3) the analysis of individual differences in brain organization for language. The hypothesis and evidence presented stem from work being performed in our laboratories

Poda selectiva de las proyecciones comisurales del colículo superior de la rata durante el desarrollo posnatal / Selective pruning of commisural projections in the superior colliculus of the rat during posnatal development

En el presente trabajo he estudiado los cambios que ocurren en proyecciones intercoliculares rata durante el desarrollo posnatal de la rata. El uso de la carbocianina DiI ha permitido marcar los axones comisurales del colículo superior. Durante el período postnatal temprano (P-1 a P-5), se observan proyecciones comisurales muy abundantes, que se distribuyen a gran parte del colículo superior contralateral. A partir del día 15 estas proyecciones se van reduciendo para adquirir, alrededor del día 30, el aspecto observado en el adulto. Existe, por lo tanto, un proceso de poda o eliminación selectiva de las proyecciones intercoliculares durante el desarrollo postnatal

Creutzfeldt-Jakob disease: report of 10 neuropathologically verified cases in Argentina

Enfermedad de Creutzfeldt-Jakob. Comunicación de 10 casos en Argentina con verificación neuropatológica. La incidencia mundial de la enfermedad de Creutzfeldt-Jakob (CJ) es dealrededor de un caso por millón de población por año. A pesar de nuestra proximidad con Chile, donde la incidencia es alta, las comunicaciones en nuestro medio alcanzan a 9 casos desde 1945 a 1980. Se presenta una serie de 10 casos de CJ con confirmación neuropatológica por biopsia cerebral y/o autopsia, nueve de ellos estudiados a partir de la creación de un Centro Neuropatológico Nacional de Referencia de Enfermedades por "virus lentos". El rango de edad de los pacientes fue de 42 a 63 años, correspondiendo la mitad de los casos a la 6ta. década. La distribución por sexo fue de 3 mujeres y 7 varones. La duración de la enfermedad fue de 3,5 a 24 meses, con una media de 10,4 meses. Todos los casos fueron esporádicos (el caso 2 tenía antecendentes neurológicos paternos poco claros). Ocho de los diez pacientes eran argentinos, los otros dos eran chilenos de nacimiento, que emigraron a la Argentina 26 años previos al comienzo de los síntomas (caso 9) y 6 meses antes de su fallecimiento (caso6). El caso 7 visitó Chile periódicamente. De los 8 argentinos, 5 eran residentes de Buenos Aires, Capital, y 3 de Córdoba, Rosario y Mar del Plata. Los casos 6 y 9 presentaban como antecendente de interés la ingestión, con relativa frecuencia, de cerebro de oveja. Los síntomas prodrómicos consistieron esencialmente en trastornos...

Localización ultraestructural de la aspartato aminotransferasa (cAATasa) en corteza cerebelosa de rata / Ultrastructural localization of the aspartate aminotransferase (cAAtse) in rat cerebelous cortex

Se ha investigado la localización de la cAAt con el método inmunocitoquímico a nivel de microscopía electrónica en la corteza cerebelosa de la rata. Las observaciones realizadas demostraron la presencia de esta enzima en algunas sinapsis excitadoras y en todas las sinapsis inhibidoras. Se discute el papel que podría desempeñar la enzima en la neurotrasmisión