RESUMEN

It has been demonstrated that rat litter size affects the immune cell response, but it is not known whether the long-term effects aggravate age-related memory impairments or microglial-associated changes. To that end, we raised sedentary Wistar rats that were first suckled in small or large litters (6 or 12pups/dam, respectively), then separated into groups of 2-3 rats from the 21st post-natal day to study end. At 4months (young adult) or 23months (aged), all individual rats were submitted to spatial memory and object identity recognition tests, and then sacrificed. Brain sections were immunolabeled with anti-IBA-1 antibodies to selectively identify microglia/macrophages. Microglial morphological changes in the molecular layer of the dentate gyrus were estimated based on three-dimensional reconstructions. The cell number and laminar distribution in the dentate gyrus was estimated with the stereological optical fractionator method. We found that, compared to young rat groups, aged rats from large litters showed significant increases in the number of microglia in all layers of the dentate gyrus. Compared to the microglia in all other groups, microglia in aged individuals from large litters showed a significantly higher degree of tree volume expansion, branch base diameter thickening, and cell soma enlargement. These morphological changes were correlated with an increase in the number of microglia in the molecular layer. Young adult individuals from small litters exhibited preserved intact object identity recognition memory and all other groups showed reduced performance in both spatial and object identity recognition tasks. We found that, in large litters, brain development was, on average, associated with permanent changes in the innate immune system in the brain, with a significant impact on the microglial homeostasis of aged rats.

Asunto(s)

Forma de la Célula/fisiología , Giro Dentado/citología , Tamaño de la Camada , Aprendizaje por Laberinto/fisiología , Trastornos de la Memoria/fisiopatología , Microglía/citología , Factores de Edad , Animales , Recuento de Células , Giro Dentado/inmunología , Trastornos de la Memoria/inmunología , Microglía/inmunología , Ratas , Ratas Wistar , Reconocimiento en Psicología/fisiología

RESUMEN

AIMS: We investigated how different nutritional states resulting from distinct lactation conditions modulate the effects of cortical electrical stimulation (CES) on the excitability-related phenomenon known as cortical spreading depression (CSD). MAIN METHODS: Wistar rats were reared in different litter sizes with 12, 6 or 3 pups, designated as malnourished (M), well-nourished (W) and overnourished (Ov), respectively. CSD was recorded for 4h on 2 cortical points of each cerebral hemisphere at baseline and after CES. CES was applied for 20 min on the left cortex using a bipolar electrode placed between the CSD recording electrodes. Paired Student t test and ANOVA followed by Tukey test were used for statistical analysis (p<0.05). KEY FINDINGS: The lactation conditions significantly influenced body weight (the M and Ov groups presented the lowest and largest average weight, respectively) and modified the CSD velocities of propagation in adulthood (Ov

Asunto(s)

Encéfalo/metabolismo , Depresión de Propagación Cortical/fisiología , Lactancia/fisiología , Desnutrición/complicaciones , Estado Nutricional/fisiología , Análisis de Varianza , Animales , Peso Corporal , Modelos Animales de Enfermedad , Estimulación Eléctrica , Femenino , Masculino , Ratas , Ratas Wistar

RESUMEN

OBJECTIVES: We review the main adverse effects of reactive oxygen species (ROS) in the mammalian organism, introducing the reader on the worldwide problem of the ROS neurophysiological impact on the developing and the adult brain, and discussing the neuroprotective action of antioxidant molecules. METHODS: We briefly present the electrophysiological phenomenon designated as 'cortical spreading depression' (CSD), as a parameter of normal brain functioning. We highlight recent electrophysiological advances obtained in experimental studies from our laboratory and from others, showing how to investigate the ROS effects on the brain by using the CSD phenomenon. RESULTS: Under conditions such as aging, ROS production by photo-activation of dye molecules and ethanol consumption, we describe the effects, on CSD, of treating animals with (1) antioxidants and (2) with antioxidant-deficient diets. DISCUSSION: The current understanding of how ROS affect brain electrophysiological activity and the possible interaction between these ROS effects and those effects of altered nutritional status of the organism are discussed.

Asunto(s)

Envejecimiento/efectos de los fármacos , Antioxidantes/farmacología , Encéfalo/efectos de los fármacos , Depresión de Propagación Cortical/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Encéfalo/fisiopatología , Dieta , Fenómenos Electrofisiológicos/efectos de los fármacos , Humanos , Estado Nutricional

RESUMEN

Spreading depression (SD) consists of a transient significant suppression of the spontaneous neural electrical activity that spreads slowly across regions of the gray matter in a wave form. Nowadays, this phenomenon is being studied by means of mathematical and computational models to reproduce the main characteristics of SD. Given the high number of parameters and their unknown ranges of variation, the setting of parameters for current SD models is usually a hard task that must be addressed in order to make such models reproduce real data. In this paper, we present a 1-D model which is able to reproduce the most important characteristics of SD waves observed in laboratory experiments: the slow extracellular potential shift and extracellular ionic concentration variations regarding speed, shape, and amplitude. Such a reproduction is possible due to a methodology that we introduced to set the parameters of the SD models. The methodology allows the impact of each parameter on the results produced by the model and the range of parameters for which the model displays plausible behavior to be determined. The methodology also helps to identify features that the model cannot produce and it gives insights about what parts of the model should be modified to improve its capacities through the identification of parameters involved with each behavior.

Asunto(s)

Corteza Cerebral/fisiología , Depresión de Propagación Cortical/fisiología , Modelos Neurológicos , Animales , Simulación por Computador , Ratas

RESUMEN

L-Arginine (ARG) is the precursor of the nitric oxide (NO) synthesis. NO-mediated signaling seems to be involved in the phenomenon of cortical spreading depression (CSD). Here, well-nourished and malnourished rats were treated, by gavage, with 150, 300 or 450 mg/kg/day of L-arginine from postnatal days 7-28, and CSD propagation was analyzed at 30-40 days. Compared to non-treated ('naïve') and water-treated controls, ARG-treated rats dose-dependently displayed higher CSD-velocities (P<0.05). In the malnourished rats, only the highest ARG-dose (450 mg/kg/day) increased CSD velocities. The mean +/- SD CSD-velocities (in mm/min) were: for well-nourished rats, 3.77 +/- 0.15, 3.78 +/- 0.23, 4.03 +/- 0.16, 4.36 +/- 0.19 and 4.41 +/- 0.26, in the naïve-, water-controls, 150, 300 and 450 mg/kg/day ARG-groups, respectively; for the same conditions in the malnourished rats, the velocities were 4.18 +/- 0.13, 4.22 +/- 0.09, 4.24 +/- 0.10, 4.27 +/- 0.21 and 4.64 +/- 0.22, respectively. Results demonstrate a dose- and nutrition-dependent CSD-facilitation by L-arginine administered during brain development. It is suggested that this effect is due to the modulation of nitric oxide synthesis.

Asunto(s)

Arginina/administración & dosificación , Encéfalo/crecimiento & desarrollo , Depresión de Propagación Cortical/efectos de los fármacos , Desnutrición/fisiopatología , Animales , Peso Corporal , Relación Dosis-Respuesta a Droga , Masculino , Óxido Nítrico/biosíntesis , Tamaño de los Órganos , Ratas , Ratas Wistar

RESUMEN

Pups were subjected to malnutrition by feeding the lactating mothers a multi-deficient (8% protein content) diet, known as regional basic diet (RBD), from birth up to weaning. The weanings were fed the same diet until 60 days of age. Ultrastructure of the optic nerve was analyzed at postnatal (P) day P8, P13, P21, P30 and P60. Electron microscopy revealed that at P8 the process of myelination has not started yet in neither groups. At P 13 different stages of myelination were observed and, in the experimental group, the optic nerve showed non-organized axon bundles and empty spaces. Control optic nerve at P21 exhibited axons with fully developed myelin sheath; whereas malnourished group had many axons being enveloped by myelin with anomalous alteration. These alterations were present in malnourished group at P30 and P60. Quantitative analysis showed statistically significant difference between control and malnourished groups when compared to the percentage of myelinated axons, axons with myelin anomalous alterations (MAA) and non-myelinated axons. Also, the myelin area was significantly smaller in malnourished groups when compared to control group. Finally, a high percentage of large non-myelinated fibers were found in the malnourished group. In conclusion, our results show that early malnutrition by a multideficient diet (RBD) affects permanently the optic nerve organization and myelination, indicating an impairment of nerve transmission and a probable dysfunction in the visual ability.

Asunto(s)

Desnutrición/patología , Vaina de Mielina/patología , Nervio Óptico/ultraestructura , Envejecimiento , Animales , Axones/ultraestructura , Proteínas en la Dieta/administración & dosificación , Femenino , Lactancia , Microscopía Electrónica , Vaina de Mielina/fisiología , Vaina de Mielina/ultraestructura , Ratas , Ratas Wistar , Pérdida de Peso

RESUMEN

We investigated in young rats the effects of malnutrition on the main structures of the circadian timing system: retina, hypothalamic suprachiasmatic nuclei (SCN), thalamic intergeniculate leaflet, retinohypothalamic- and geniculohypothalamic tracts. Control rats were born from mothers fed a commercial diet since gestation, and malnourished rats from mothers fed a multideficient diet since gestation (GLA group) or lactation (LA group). After weaning, pups received the same diet as their mothers, and were analysed at postnatal days 27, 30-33 and 60-63. Brain sections were processed to visualise in the SCN neuropeptide Y immunoreactivity and terminal labeling after intraocular tracer injections. Nissl staining was used to assess cytoarchitectonic boundaries of the SCN and cell features in retinal whole mounts. Cell counts, morphometric and densitometric analysis were performed. Compared with controls, the total retinal surface was reduced and the topographical distribution of retinal ganglion cells was altered in malnourished rats, with changes in their density. Alterations were also detected in the SCN dimensions in the GLA and LA groups at one and two postnatal months, as well as in the SCN portion occupied by the retinal input in the GLA group at days 30-33, but not in the NPY-containing geniculohypothalamic tract. The present data point to subtle changes, with a low and differential vulnerability to early malnutrition, of structures involved in circadian timing regulation. Furthermore, the present findings suggest that the altered circadian rhythmicity previously documented in malnourished rats cannot be ascribed to impaired development of the retino- and geniculohypothalamic projections to the SCN.

Asunto(s)

Encéfalo/patología , Cuerpos Geniculados/patología , Desnutrición/patología , Retina/patología , Núcleo Supraquiasmático/patología , Factores de Edad , Animales , Animales Recién Nacidos , Peso Corporal/fisiología , Encéfalo/citología , Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Recuento de Células/métodos , Tamaño de la Célula , Femenino , Cuerpos Geniculados/anatomía & histología , Cuerpos Geniculados/crecimiento & desarrollo , Cuerpos Geniculados/metabolismo , Inmunohistoquímica/métodos , Lactancia , Masculino , Vías Nerviosas/crecimiento & desarrollo , Vías Nerviosas/patología , Neuronas/metabolismo , Neuronas/patología , Neuropéptido Y/metabolismo , Tamaño de los Órganos/fisiología , Ratas , Ratas Wistar , Retina/citología , Retina/crecimiento & desarrollo , Retina/metabolismo , Factores Sexuales , Coloración y Etiquetado/métodos , Núcleo Supraquiasmático/crecimiento & desarrollo , Núcleo Supraquiasmático/metabolismo

RESUMEN

We investigated the somatic maturation of neonate rats treated during the suckling period with citalopram, a selective serotonin reuptake inhibitor. Groups with 6 male neonates were randomly assigned to different treatments 24 h after birth. Each litter was suckled by one of the dams until the 21st postnatal day. Body weight, head axis and tail length were measured daily from the 1st to the 21st postnatal day. Time of ear unfolding, auditory conduit opening, incisor eruption, and eye opening was determined. Pups received 5 mg (Cit5), 10 mg (Cit10) or 20 mg/kg (Cit20) citalopram sc, or saline (0.9 percent NaCl, w/v, sc). Compared to saline, body weight was lower (24.04 percent, P < 0.01) for Cit10 from the 10th to the 21st day and for Cit20 from the 6th to the 21st day (38.19 percent, P < 0.01). Tail length was reduced in the Cit20 group (15.48 percent, P < 0.001) from the 8th to the 21st day. A reduction in mediolateral head axis (10.53 percent, P < 0.05) was observed from the 11th to the 21st day in Cit10 and from the 6th to the 21st day in Cit20 (13.16 percent, P < 0.001). A reduction in anteroposterior head axis was also observed in the Cit20 group (5.28 percent, P < 0.05) from the 13th to the 21stday. Conversely, this axis showed accelerated growth from the 12th to the 21stday in the Cit5 group (13.05 percent, P < 0.05). Auditory conduit opening was delayed in the Cit5 and Cit20 groups and incisor eruption was delayed in all citalopram groups. These findings show that citalopram injected during suckling to rats induces body alterations and suggest that the activity of the serotoninergic system participates in growth mechanisms.

Asunto(s)

Animales , Masculino , Femenino , Ratas , Animales Recién Nacidos , Animales Lactantes , Citalopram , Inhibidores Selectivos de la Recaptación de Serotonina , Aumento de Peso , Ratas Wistar , Cola (estructura animal)/crecimiento & desarrollo , Factores de Tiempo

RESUMEN

We investigated the somatic maturation of neonate rats treated during the suckling period with citalopram, a selective serotonin reuptake inhibitor. Groups with 6 male neonates were randomly assigned to different treatments 24 h after birth. Each litter was suckled by one of the dams until the 21st postnatal day. Body weight, head axis and tail length were measured daily from the 1st to the 21st postnatal day. Time of ear unfolding, auditory conduit opening, incisor eruption, and eye opening was determined. Pups received 5 mg (Cit5), 10 mg (Cit10) or 20 mg/kg (Cit20) citalopram sc, or saline (0.9% NaCl, w/v, sc). Compared to saline, body weight was lower (24.04%, P < 0.01) for Cit10 from the 10th to the 21st day and for Cit20 from the 6th to the 21st day (38.19%, P < 0.01). Tail length was reduced in the Cit20 group (15.48%, P < 0.001) from the 8th to the 21st day. A reduction in mediolateral head axis (10.53%, P < 0.05) was observed from the 11th to the 21st day in Cit10 and from the 6th to the 21st day in Cit20 (13.16%, P < 0.001). A reduction in anteroposterior head axis was also observed in the Cit20 group (5.28%, P < 0.05) from the 13th to the 21st day. Conversely, this axis showed accelerated growth from the 12th to the 21st day in the Cit5 group (13.05%, P < 0.05). Auditory conduit opening was delayed in the Cit5 and Cit20 groups and incisor eruption was delayed in all citalopram groups. These findings show that citalopram injected during suckling to rats induces body alterations and suggest that the activity of the serotoninergic system participates in growth mechanisms.

Asunto(s)

Animales Recién Nacidos/crecimiento & desarrollo , Animales Lactantes/crecimiento & desarrollo , Citalopram/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Aumento de Peso/efectos de los fármacos , Animales , Femenino , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Cola (estructura animal)/crecimiento & desarrollo , Factores de Tiempo

RESUMEN

A few months ago, the Brazilian Society for Neuroscience and Behavior (SBNeC) promoted a "virtual symposium" (by Internet, under the coordination of R.C.A. Guedes) on "Nutrition and Brain Function". The discussions generated during that symposium originated the present text, which analyzes current topics on the theme, based on the multidisciplinary experience of the authors. The way the brain could be non-homogeneously affected by nutritional alterations, as well as questions like early malnutrition and the development of late obesity and hormone abnormalities were discussed. Also, topics like the role of essential fatty acids (EFAs) on brain development, increased seizure susceptibility and changes in different neurotransmitters and in cognitive performance in malnourished animals, as well as differences between overall changes in nutrient intake and excess or deficiency of specific nutrients (e.g. iodine deficiency) were analyzed. It was pointed out that different types of neurons, possibly in distinct brain structures, might be differently affected by nutritional manipulation, including not only lack-but also excess of nutrient intake. Such differences could help in explaining discrepancies between data on humans and in animals and so, could aid in determining the basic mechanisms underlying lesions or changes in brain function and behavior.

Asunto(s)

Encéfalo/fisiología , Trastornos Nutricionales/complicaciones , Fenómenos Fisiológicos de la Nutrición , Interfaz Usuario-Computador , Humanos , Internet , Yodo/deficiencia , Convulsiones/etiología

RESUMEN

The aim of the present study was to determine the effect of a regional basic diet (RBD) on the prevalence of caries in the molar teeth of rats of both sexes aged 23 days. The animals were divided into six groups of 10 rats each receiving the following diets for 30 and 60 days after weaning: RBD, a cariogenic diet, and a commercial diet. The prevalence and penetration of caries in the molar teeth of the rats was then analyzed. The RBD produced caries in 37.5% of the teeth of animals fed 30 days, and in 83.4% of animals fed 60 days, while the cariogenic diet produced caries in 72.5% and 77.5% of the teeth of animals fed 30 and 60 days, respectively. Rats fed the RBD for 30 days had caries in the enamel in 38% of their teeth, 48% had superficial dentin caries, and 7.5% moderate dentin caries. The effect of the RBD did not differ significantly from that of the cariogenic diet in terms of the presence of caries in rats fed 60 days. The penetration depth of the caries produced by the RBD was the same as that produced by the cariogenic diet. Our results show that the RBD has the same cariogenic potential as the cariogenic diet. Since the RBD is the only option for the low-income population, there should be a study of how to compensate for the cariogenicity of this diet.

Asunto(s)

Cariogénicos/efectos adversos , Caries Dental/etiología , Dieta Cariógena , Animales , Brasil , Caries Dental/prevención & control , Pruebas de Actividad de Caries Dental , Femenino , Masculino , Prevalencia , Ratas , Ratas Wistar

RESUMEN

The aim of the present study was to determine the effect of a regional basic diet (RBD) on the prevalence of caries in the molar teeth of rats of both sexes aged 23 days. The animals were divided into six groups of 10 rats each receiving the following diets for 30 and 60 days after weaning: RBD, a cariogenic diet, and a commercial diet. The prevalence and penetration of caries in the molar teeth of the rats was then analyzed. The RBD produced caries in 37.5 percent of the teeth of animals fed 30 days, and in 83.4 percent of animals fed 60 days, while the cariogenic diet produced caries in 72.5 percent and 77.5 percent of the teeth of animals fed 30 and 60 days, respectively. Rats fed the RBD for 30 days had caries in the enamel in 38 percent of their teeth, 48 percent had superficial dentin caries, and 7.5 percent moderate dentin caries. The effect of the RBD did not differ significantly from that of the cariogenic diet in terms of the presence of caries in rats fed 60 days. The penetration depth of the caries produced by the RBD was the same as that produced by the cariogenic diet. Our results show that the RBD has the same cariogenic potential as the cariogenic diet. Since the RBD is the only option for the low-income population, there should be a study of how to compensate for the cariogenicity of this diet

Asunto(s)

Animales , Masculino , Femenino , Ratas , Cariogénicos , Caries Dental , Dieta , Brasil , Caries Dental , Pruebas de Actividad de Caries Dental , Dieta Cariógena , Diente Molar , Prevalencia , Ratas Wistar

RESUMEN

The effect of early postnatal malnutrition upon food intake and its modulation by the selective serotonin reuptake inhibitor (SSRI) citalopram, was investigated in adult rats. Sixty four Wistar rats were allocated to two groups, according to their mother's diet during lactation. Mothers receiving a 23% protein diet fed the well-nourished group; mothers receiving 8% protein diet fed the malnourished. After weaning, all rats received the 23% protein diet ad libitum. On the 120th day after birth, each nutritional group was divided in two subgroups (each one, n = 16) which received a single daily injection of citalopram (10 mg/kg) or saline (0.9% NaCl) for 14 days. Chronic treatment with citalopram decreased both the food intake and weight gain in the well-nourished rats, but not in the malnourished ones. These data are consistent with findings concerning the nutritional manipulation of the nervous system during its higher vulnerable phase, suggesting that early malnutrition alters the effect of treatment of SSRI in adult rats, and that malnutrition during the critical period of brain development affects the serotoninergic system.

Asunto(s)

Anorexia/inducido químicamente , Citalopram/administración & dosificación , Deficiencia de Proteína/fisiopatología , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Animales , Proteínas en la Dieta/administración & dosificación , Ingestión de Alimentos/efectos de los fármacos , Lactancia , Masculino , Ratas , Ratas Wistar , Serotonina/fisiología , Aumento de Peso/efectos de los fármacos

RESUMEN

Adult, well-nourished (W) and early-malnourished (M) male Wistar rats were injected intraperitoneally for 7 days with 20 mg/kg CIT and cortical spreading depression (CSD) was recorded for 4 h on the day following the treatment. M-animals presented lower body weights, as well as higher CSD velocities of propagation, than the W ones, as previously reported. Compared to saline-injected controls, rats treated with CIT for 7 days presented comparable body weights and lower mean CSD velocities, per hour of recording, the differences being significant at the second hour (3.29+/-0.31 versus 3.56+/-0.40 mm/min; P < 0.05). Topical, cortical application of CIT (1- and 5 mg/ml solutions over the intact dura-mater) reduced dose-dependently the CSD velocity (maximal reductions of 16.3 and 55.8% for the 1 and 5 mg/ml solutions, respectively; P < 0.05), as well as the amplitude of the CSD-slow potential change (58.2 and 88.3%). In three out of seven W-rats and in one out of seven M-rats, topical CIT (5 mg/ml) blocked CSD propagation. The effects were reverted by flushing the treated region with saline. In the M-groups, CIT affected CSD in the same manner as in the W ones. The results reinforce previous evidence for an antagonistic influence of the serotoninergic activity on CSD.

Asunto(s)

Citalopram/farmacología , Depresión de Propagación Cortical/efectos de los fármacos , Trastornos Nutricionales/fisiopatología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Animales , Peso Corporal , Inyecciones Intraperitoneales , Masculino , Ratas

RESUMEN

Most studies suggest that serotonin exerts an inhibitory control on the aggression process. According to experimental evidence, this amine also influences growth and development of the nervous tissue including serotoninergic neurons. Thus, the possibility exists that increased serotonin availability in young animals facilitates a long-lasting effect on aggressive responses. The present study aimed to investigate the aggressive behavior of adult rats (90-120 days) treated from the 1st to the 19th postnatal day with citalopram (CIT), a selective serotonin reuptake inhibitor (20 mg/kg, sc, every 3 days). Aggressive behavior was induced by placing a pair of rats (matched by weight) in a box (20 x 20 x 20 cm), and submitting them to a 20-min session of electric footshocks (five 1.6-mA - 2-s current pulses, separated by a 4-min intershock interval). When compared to the control group (rats treated for the same period with equivalent volumes of saline solution), the CIT group presented a 41.4 percent reduction in the duration of aggressive response. The results indicate that the repeated administration of CIT early in life reduces the aggressive behavior in adulthood and suggest that the increased brain serotoninergic activity could play a role in this effect

Asunto(s)

Animales , Masculino , Ratas , Agresión/efectos de los fármacos , Citalopram/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Animales Recién Nacidos , Peso Corporal , Distribución Aleatoria , Ratas Wistar , Factores de Tiempo

RESUMEN

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 percent protein) of low-income human population 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 percent 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 percent protein, early malnourished rats showed deficits in body and brain weights (10 percent to 60 percent and 3 percent to 15 percent, respectively), as well as increases in velocity of SD propagation (10 percent to 20 percent). these effects were directly related to the duration of maternal dietary restriction, with pups malnourished for 2 ou 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.

Asunto(s)

Ratas , Animales , Femenino , Peso Corporal/fisiología , Depresión de Propagación Cortical/fisiología , Lactancia/fisiología , /fisiopatología , Electroencefalografía , /complicaciones , Ratas Wistar

RESUMEN

The effects of aging on spreading depression (SD) were investigated in the Mongolian gerbil (G; age range 1.5 to 58 months; N = 35) and in the albino rat (R; 2.5 to 24 months; N = 100). Two strains of rats were studied: Wistar (W; N = 35) and Sprague-Dawley (SDAW; N = 65). SDAW rats were divided into two groups: one group was fed a commercial lab chow diet (CD) containing 22 per cent protein (N = 47), and the other was fed a 22 per cent casein diet (CAS; N = 18). SD was elicited on the frontal cortical surface by 1-min application of 2 per cent KCl and its appearance was recorded (ECoG and DC potential) at two points in the parieto-occipital area of the same hemisphere. SD propagation velocity was measured on the basis of the time spent for an SD "wave" to cross the distance between the two recording points. Within the age range studied, older animals displayed significantly lower SD velocities than the younger ones, independent of the species, strain or diet (velocity ranges, in mm/min: G, 2.22-5.99; W, 2.47-4.12; SDAW-CD, 2.32-4.42 and SDAW-CAS, 2.65-4.14). The correlation coefficients between age and SD velocity were: G, -0.78; W, -0.45; SDAW-CD, -0.68 and SDAW-CAS, -0.72 (P<0.05 in all cases). As a rule, at each time point the gerbils presented higher SD velocities than the rats of the same age. In another set of experiments, in order to test the role of free radicals in SD, 7 gerbils (14-51 months old) and 13 W rats (3-24 months old) were fed a 22 per cent casein diet free of the antioxidant vitamins C and E for 4-6 weeks before the experiments. No correlation was found between age and SD propagation in these animals fed a diet free of vitamins C and E, although gerbils displayed higher SD velocities than age-matched rats (velocities: G, 3.70-5.34; R, 3.25-4.44 mm/min; correlation coefficients: G, -0.39; W, -0.29; P>0.05). These data indicate that gerbils have higher SD susceptibility than rats of the same age, and that this susceptibility decreases with aging in both species. The lack of correlation between age and SD velocity in the animals fed a diet free of antioxidant vitamins suggests a possible role of free radicals in cortical SD, in accordance with evidence from other laboratories obtained in the isolated retina.

Asunto(s)

Ratas , Animales , Envejecimiento/fisiología , Antioxidantes/metabolismo , Depresión de Propagación Cortical/fisiología , Dietoterapia , Gerbillinae , Ratas Sprague-Dawley , Ratas Wistar

RESUMEN

We investigated the effect of a single ip injection of ed-fenfluramine (d-fen; 5-10 mg/kg), a serotinin reuptake blocker, on cortical spreading depression (SD) in 17 male Wistar rats (300-360 g body weight). SD was elicited at the right frontal cortex by 1-min application of 2 percent KCl at 20-min intervals. SD propagation was monitored (electrocorticogram and DC-recording) at 2 points on the right parietal surface for 3 h. After a "baseline" recording period (1 h), d-fen was injected and the recording session was continued for 2 h. When compared to the predrug SD velocities (t = 0 min) the values measured after d-fen decreased significantly at t = 20 min (3.44 + or - 0.63 vs 2.66 + or - 0.51 mm/min; N = 17, P<0.001), at t = 40 min (3.32 + or - 0.58 vs 2.53 + or - 0.52 mm/min; N = 14, P<0.001), att=60 min (3.68 + or - 0.63 vs 2.92 + or - 0.72 mm/min; N = 11, P<0.001) and at t = 80 min (3.57 + or - 0.61 vs 3.03 + or - 0.83 mm/min; N = 12, P<0.05) but not at t = 100 min (3.47 + or - 0.72 vs 3.31 + or - 0.88 mm/min; N = 12) nor at t = 120 min (3.44 + or - 0.67 vs 3.37 + or - 0.76 mm/min; N = 11). Furthermore, in 19 of 48 KCl stimulations (40 percent) performed ...

Asunto(s)

Animales , Masculino , Ratas , Depresión de Propagación Cortical , Fenfluramina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Depresión de Propagación Cortical/fisiología , Electrofisiología , Fenfluramina/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Ratas Wistar

RESUMEN

The effect of treatment with propylthiouracil early in life (PTU; 8 mg k-1 day-1, ip, from day 17 of gestation to postnatal day 42) on the susceptibility of the cerebral cortex to spreading depression (SD) was studied in 13 adult Wistar rats (90-100 days of age). Ten animals injected with Ringer solution served as control. Adult PTU-treated rats displayed a significant (P < 0.05) reduction in body weight (mean +/- SD: 139.9 +/- 28.9 g vs 304.9 +/- 42.8 g) as well as wet brain weight (1.39 +/- 0.12 g vs 1.86 +/- 0.13 g) and dry brain weight (247.3 +/- 24.2 mg vs 359.4 +/- 30.1 mg). Their thyroid glands presented histological changes indicative of hypofunction and SD velocity of propagation was significantly reduced all along the 6 h of the recording session (mean +/- SD ranges: 1.90 +/- 0.46 to 2.52 +/- 0.68 mm/min vs 3.49 +/- 0.57 to 3.71 +/- 0.55 mm/min). The results indicate that PTU early in life was effective in producing hypothyroidism and that in this situation cortical susceptibility to SD is impaired

Asunto(s)

Animales , Femenino , Embarazo , Ratas , Depresión de Propagación Cortical , Glándula Tiroides/fisiología , Propiltiouracilo/farmacología , Peso Corporal , Cerebro/anatomía & histología , Glándula Tiroides/patología , Tamaño de los Órganos , Ratas Wistar

RESUMEN

The effect of ip anesthesia with urethane + chloralose (U + C, 1,0 g/kg) or thionembutal (TH, 40.0 mg/kg) on the velocity of propagation of cortical spreading depression was studied in adult Wistar rats. We also describe a technique for measuring the spreading depression propagation rate based on implanting insulated silver wires into the right parietal region, whose silver chloride tips are in contact with the cortical surface. The propagation rate was measured in the same animals during (mean ñ SEM, mm/min: 2.69 ñ 0.17 for U C, N =9, and 2.60 ñ 0.09 for TH, N =7) and after (3.23 ñ 0.13 for U C and 3.84 ñ 0.18 for TH) anesthesia. The rate was significantlyhigher for rats in the awake condition. The second administration of anesthesia to the same rats decreased the velocity of spreading depression again (2.01 ñ 0.38 for U + C, N=7, and 2.96 ñ 0.18 for TH, N=7). The effects of TH and U + C on the rate of propagation were reversed 24 and 48 hours after anesthesia, respectively. We conclude that the technique proposed is adequate for measuring the velocity of spreading depression in unanesthetized rats and that U + C and TH reduce the propagation velocity

Asunto(s)

Anestesia/efectos adversos , Barrera Hematoencefálica , Cloralosa , Depresión de Propagación Cortical , Uretano , Cerebro/fisiología , Electrofisiología , Potenciales Evocados