Litter size, age-related memory impairments, and microglial changes in rat dentate gyrus: stereological analysis and three dimensional morphometry.

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.

Favorable and unfavorable lactation modulates the effects of electrical stimulation on brain excitability: a spreading depression study in adult rats.

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

The use of cortical spreading depression for studying the brain actions of antioxidants.

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.

Modeling the slow wave shapes of spreading depression in a rat cortex: a methodology for seeking physiological parameters.

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.

L-Arginine administration during rat brain development facilitates spreading depression propagation: evidence for a dose- and nutrition-dependent effect.

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.

Diagnóstico citológico de neoplasia pulmonar por meio de lavado broncoalveolar em uma cadela: relato de caso / Cytologic diagnosis of pulmonary neoplasm with bronchoalveolar lavage in a bitch: case report

Relata-se o caso de uma cadela de raça Poodle, de 12 anos de idade, com quadro clínico de tosse crônica não responsiva à terapia medicamentosa. O exame radiográfico mostrou imagem de consolidação do lobo pulmonar esquerdo. O exame de lavado broncoalveolar pelo broncofibroscópio mostrou células epiteliais com características de malignidade, permitindo firmar o diagnóstico de carcinoma pulmonar sem diferenciação entre neoplasia primária ou metastática.

This article reports a case of a bitch, Poodle, 12 year-old with chronic cough, which had insufficient response to medicamentous therapy. Thoracic radiographic revealed a lobar consolidation in left caudal pulmonary lobe. A bronchoalveolar lavage sample was collected by bronchoscopy for cytology examination. Malignant epithelial cells were observed through cytology allowing the diagnosis of carcinoma. The differential diagnosis between primary pulmonary neoplasm and metastatic neoplasm was not possible.

Kinetic and wet oxidation of phenol catalyzed by non-promoted and potassium-promoted manganese/cerium oxide.

The wet oxidation of organic compounds to CO2 and H2O has been shown to be a very efficient technique in the outflows treatment. This work focuses on the interaction of the chemical element potassium with the catalyst MnO2-CeO2 in the wet degradation of phenol. The reaction has been carried out in an autoclave with a controlled system of agitation, pressure, temperature and sampling of the liquid phase. The experiments were performed in the presence of the catalysts MnO2-CeO2 and K-MnO2-CeO2 in the following operational conditions: temperature of 130 degrees C, P = 20.4 atm, catalyst concentration in the range 1.5-5.0 g/L, initial phenol concentration of 0.5 g/L, initial pH varying between 6.8 and 8.5, and percentage of potassium in the catalyst MnO2-CeO2 ranging between 0% and 10%. Curves indicating the profile of conversion of total organic carbon show that the phenol degradation is favored when the potassium quantity is reduced. This behaviour is confirmed by BET analysis, whereby the catalyst presents larger specific area when compared to the percentages of other components. Regardless of the catalyst used in the phenol oxidation, the kinetic constant of reaction had the same order of magnitude for two parallel stages proposed by a first-order kinetic model.

Effect of dietary inclusion of distillers dried grains with solubles on the ability of growing pigs to resist a Lawsonia intracellularis challenge.

An experiment was conducted to determine if including distillers dried grains with solubles (DDGS) in the diet of growing pigs reduces the incidence or severity of infection after a Lawsonia intracellularis challenge. Eighty 17-d-old weaned pigs were blocked by sex, ancestry, and BW and randomly allotted to 1 of 4 treatment groups: negative control (NC), unchallenged, corn-soy diet; positive control (PC), challenged, corn-soy diet; 10% DDGS diet (10D), challenged; and 20% DDGS diet (20D), challenged. Challenged pigs were orally inoculated with 1.5 x 10(9) L. intracellularis organisms after a 4-wk prechallenge feeding period. On d 21 postchallenge, pigs were euthanized, lesions of intestinal mucosa were evaluated, and ileal tissue samples were analyzed by immunohistochemistry to determine the presence and proliferation rate of L. intracellularis. Compared with unchallenged pigs, challenging pigs with L. intracellularis reduced growth rate, feed intake, and efficiency of gain (P < 0.01) and increased gauntness (P < 0.05) and diarrhea (P < 0.01). Diet did not affect growth performance postchallenge (P > 0.40). Feeding 10 or 20% DDGS diets did not reduce lesion length, prevalence, proliferation of L. intracellularis, or severity of lesions (P > 0.10). Thus, dietary inclusion of DDGS did not reduce the incidence or severity of lesions under the conditions of a severe L. intracellularis challenge used in this study.

Effect of including distillers dried grains with solubles in the diet, with or without antimicrobial regimen, on the ability of growing pigs to resist a Lawsonia intracellularis challenge.

A disease challenge experiment was conducted to determine if including 10% dried distillers grains with solubles (DDGS) in the diet, with or without antimicrobial supplementation, reduces the incidence or severity, or both, of intestinal lesions in growing pigs after an Lawsonia intracellularis challenge. One hundred 17-d-old weaned pigs were blocked by sex, ancestry, and BW and randomly allotted to 1 of 5 treatment groups: negative control, unchallenged, corn-soy diet; positive control, challenged, corn-soy diet; 10% DDGS diet, challenged; positive control with antimicrobial regimen, challenged; and 10% DDGS diet with antimicrobial regimen, challenged. For antimicrobial-supplemented treatments, diets contained 33 ppm bacitracin methylene disalicylate throughout the experiment, with chlortetracycline (Aureomycin) pulsed at 550 ppm from d 3 prechallenge to d 11 postchallenge. Challenged pigs were orally inoculated with 8.0 x 10(8) L. intracellularis organisms after a 4-wk prechallenge period. On d 21 postchallenge, pigs were euthanized, lesions of intestinal mucosa were evaluated, and ileal tissue samples were analyzed by immunohistochemistry to determine the presence and proliferation rate of L. intracellularis. Compared with other dietary treatments, feeding a diet containing 10% DDGS reduced ileum and colon lesion length and prevalence (P < 0.05) and reduced severity of lesions in the ileum (P < 0.05) and colon (P < 0.10) in challenged pigs. Compared with other challenged pigs, those fed the diet containing the antimicrobial regimen had a lower prevalence and severity of lesions in the jejunum (P < 0.05) and tended to have reduced total tract lesion length (P = 0.11). Compared with other challenged pigs, pigs on the 10% DDGS diet with antimicrobial regimen exhibited no differences in length, severity, or prevalence of lesions (P > 0.15), but fecal shedding of L. intracellularis was reduced on d 14 postchallenge (P < 0.05). No dietary effects on fecal shedding were observed by d 20 postchallenge (P > 0.10). The proportion of cells infected with L. intracellularis was reduced when DDGS (P = 0.05) or antimicrobial (P = 0.10) diets were fed. Under the conditions of this experiment, dietary inclusion of 10% DDGS appears to provide some benefit to growing pigs subjected to a moderate L. intracellularis challenge, similar to those of a currently approved antimicrobial regimen.

Effect of dietary inclusion of distillers dried grains with solubles, soybean hulls, or a polyclonal antibody product on the ability of growing pigs to resist a Lawsonia intracellularis challenge.

An experiment was conducted to determine if dietary inclusion of distillers dried grains with solubles (DDGS), soybean hulls, or soybean hulls sprayed with an egg-based, polyclonal antibody product would reduce the incidence or severity of infection, or both, in growing pigs after a Lawsonia intracellularis challenge. One hundred 17-d-old weaned pigs were blocked by sex, ancestry, and BW, and randomly allotted to 1 of 5 treatment groups: negative control, unchallenged, corn-soy diet; positive control, challenged, corn-soy diet; 20% DDGS diet (D), challenged; 5% soybean hulls diet (SH), challenged; and SH sprayed with a polyclonal antibody product diet, challenged. Challenged pigs were orally inoculated with 6.4 x 10(8) L. intracellularis organisms after a 4-wk prechallenge feeding period. On d 21 postchallenge, pigs were euthanized, lesions of intestinal mucosa were evaluated, and ileal tissue samples were analyzed by immunohistochemistry to determine the presence and proliferation rate of L. intracellularis. Challenging pigs with L. intracellularis reduced growth rate, feed intake, and efficiency of gain (P < 0.02) and increased the proportion of internal organ weights relative to BW (P < 0.01). Dietary treatment did not affect growth performance pre- or postchallenge (P > 0.10). Heart, empty stomach, and liver weights were similar among dietary treatments (P > 0.10). Weight of the large intestine as a percentage of BW was increased in D and SH pigs compared with positive control pigs (P < 0.05). Lesion length, prevalence, and severity, and fecal shedding of L. intracellularis were primarily unaffected by dietary treatment (P > 0.10), although ileal lesion length and severity observed tended to be greater in the SH sprayed with polyclonal antibody product diet vs. the D pigs (P < 0.10). Results from a previous study indicated that diet composition may affect length, severity, and prevalence of lesions caused by L. intracellularis in growing pigs subjected to a moderate challenge. However, beneficial results were not observed by feeding the dietary treatments used in this study.

Quantitative ultrastructural evidence of myelin malformation in optic nerves of rats submitted to a multideficient diet.

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.

Differential vulnerability of the rat retina, suprachiasmatic nucleus and intergeniculate leaflet to malnutrition induced during brain development.

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.

Neonatal administration of citalopram delays somatic maturation in rats

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.

Neonatal administration of citalopram delays somatic maturation in rats.

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.

Nutrition and brain function: a multidisciplinary virtual symposium.

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.

Effect of a Brazilian regional basic diet on the prevalence of caries in rats.

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.

Effect of a Brazilian regional basic diet on the prevalence of caries in rats

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

Early malnourished rats are not affected by anorexia induced by a selective serotonin reuptake inhibitor in adult life.

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.

Citalopram has an antagonistic action on cortical spreading depression in well-nourished and early-malnourished adult rats.

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.

Cortical spreading depression during streptozotocin-induced hyperglycaemia in nutritionally normal and early-malnourished rats.

Cortical spreading depression (SD) was investigated in adult rats during Streptozotocin (STZ)-induced hyperglycaemia (group S; n=13). SD velocities of propagation were significantly lower than in the controls injected only with vehicle solution (group V; n=17). In contrast, rats rendered hypoglycaemic by food restriction+insulin for 3 days (group HG; n=9) presented SD velocities significantly higher than controls; this effect was reversed by injecting glucose during the recording session. SD velocity in early-malnourished rats was not different during STZ-hyperglycaemia (group MS; n=8) compared with previously-malnourished rats injected with vehicle (group MV; n=9). The data indicate an inverse relationship between glycaemia changes and SD propagation in well-nourished rats. Early malnutrition seems to abolish the effect of STZ-hyperglycaemia on SD.