Sepsis impairs the propagation of cortical spreading depression in rats and this effect is prevented by antioxidant extract.

Sepsis is a clinical syndrome with high morbidity and mortality. It is characterized by acute inflammatory response and oxidative stress, which is implicated in cerebral dysfunction. Murici (Byrsonimacrassifolia (L.) Kunth) is a fruit rich in antioxidant compounds, which could be an alternative to prevent damage to tissues induced by sepsis . Here, we evaluated the effects of sepsis on the propagation of cortical spreading depression (CSD) and oxidative stress, and tested the action of murici antioxidant extract in prevention against the effect of sepsis. Male Wistar rats (90-210 days, n = 40) were previously supplemented, orogastrically, with murici extract (150 mg/kg/day or 300 mg/kg/day), or an equivalent volume of the vehicle solution, for fifteen days. Then the animals were subjected to experimental sepsis through cecal ligation and perforation (CLP). Subsequently, CSD recordings were obtained and brain oxidative stress was evaluated. Sepsis decelerated CSD and increased the malondialdehyde (MDA) levels in the brain cortex of the animals. In contrast, septic rats that had been previously supplemented with murici antioxidant extract in doses of 150 and 300 mg/kg/day showed an increase in CSD propagation velocity, low levels of MDA and GSH/GSSG ratio and an increase of superoxide dismutase (SOD) activity, regardless of the dose tested. Our results demonstrate that sepsis affects brain excitability and that this effect can be prevented by murici antioxidant extract. The effects of sepsis and/or murici extract on CSD may be due to the oxidative state of the brain.

Physical exercise counteracts the increase in velocity of propagation of cortical spreading depression imposed by early over-nutrition in rats.

Objectives: This investigation studied whether physical exercise could modulate cortical spreading depression (CSD) propagation velocity in adult rat offspring from dams that had received a high-fat (HF) diet during lactation. Methods: Wistar male rats suckled by dams fed either control (C) or HF diet ad libitum. After weaning, pups received standard laboratory chow. From 40 to 60 days of life, half of the animals exercised on a treadmill (group E); the other half remained sedentary (group S). Two additional HF groups (E and S) received fluoxetine (F; 10 mg/kg/day, orogastrically) from 40 to 60 days of life (groups HF/EF and HF/F). Results: At 40 days of life, rats from the maternal HF diet presented higher weight, thoracic circumference, and Lee Index than C animals and remained heavier at 60 days of life. Physical exercise decreased abdominal circumference. HF diet increased CSD propagation velocity (mean ± SD; mm/min) in sedentaries (HF/S 3.47 ± 0.31 versus C/S 3.24 ± 0.26). Treadmill exercise decelerated CSD propagation in both groups C/E (2.94 ± 0.28) and HF/E (2.97 ± 0.40). Fluoxetine alone decreased CSD propagation (HF/F 2.88 ± 0.45) compared with HF/S group. The combination of fluoxetine + exercise under HF condition (2.98 ± 0.27) was similar to HF/E group. Discussion: Physical exercise is able to reduce CSD propagation velocity in rat adult brains even when they have suffered over-nourishing during lactation. The effects of exercise alone or fluoxetine alone on CSD were similar to the effects of fluoxetine + exercise, under the HF condition. Data reinforce malnutrition during lactation modifies cortical electrophysiology even when the HF condition no longer exists.

Antioxidant extract counteracts the effects of aging on cortical spreading depression and oxidative stress in the brain cortex.

PURPOSE: To investigate the effects of Murici extract on the brain excitability-dependent phenomenon known as cortical spreading depression (CSD) and on brain oxidative stress. METHODS: Adult and aged Wistar rats were supplemented with murici extract (150 mg/kg/day or 300 mg/kg/day) by gavage for fifteen days. Afterwards, the animals were submitted to a CSD electrophysiological recording and to brain oxidative stress evaluation. RESULTS: Our results showed that aging decreased CSD propagation velocity, catalase activity and glutathione/oxidized glutathione ratio (GSH/GSSG) in the brain cortex of the rats, and increased malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) activity. The highest dose (300 mg/kg/day) of murici extract accelerated CSD, whereas the lowest (150mg/kg/day) decelerated, in both adult and aged animals. In contrast, aged animals supplemented with murici extract in both doses presented low MDA levels and high GSG/GSSG ratio in comparison to the control-aged animals. CONCLUSION: Murici extract supplementation seems to revert detrimental effects in aged brains and could be considered as a strategy in the treatment of pathologies related to aging and cortical spreading depression.

Antioxidant extract counteracts the effects of aging on cortical spreading depression and oxidative stress in the brain cortex

Abstract Purpose: To investigate the effects of Murici extract on the brain excitability-dependent phenomenon known as cortical spreading depression (CSD) and on brain oxidative stress. Methods: Adult and aged Wistar rats were supplemented with murici extract (150 mg/kg/day or 300 mg/kg/day) by gavage for fifteen days. Afterwards, the animals were submitted to a CSD electrophysiological recording and to brain oxidative stress evaluation. Results: Our results showed that aging decreased CSD propagation velocity, catalase activity and glutathione/oxidized glutathione ratio (GSH/GSSG) in the brain cortex of the rats, and increased malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) activity. The highest dose (300 mg/kg/day) of murici extract accelerated CSD, whereas the lowest (150mg/kg/day) decelerated, in both adult and aged animals. In contrast, aged animals supplemented with murici extract in both doses presented low MDA levels and high GSG/GSSG ratio in comparison to the control-aged animals. Conclusion: Murici extract supplementation seems to revert detrimental effects in aged brains and could be considered as a strategy in the treatment of pathologies related to aging and cortical spreading depression.

Interferência da L-arginina e do exercício físico sobre a morfologia do músculo estriado esquelético em ratos jovens / L-arginine and physical exercise interference on the morphology of the skeletal muscle in young rats

INTRODUÇÃO: O exercício físico pode promover alterações anatomofisiológicas no músculo estriado esquelético e a ingestão do aminoácido L-arginina pode influenciar na morfometria da fibra muscular esquelética. OBJETIVO: Analisar a influência da L-arginina associada ao exercício físico sobre a fibra muscular esquelética. MÉTODOS: Foram utilizados 24 ratos da linhagem Wistar. Aos sete dias de vida, esses animais foram divididos em dois grupos: tratados com L-arginina (grupo-Ar; 300 mg/kg/dia) e tratados com volume equivalente do veículo - água destilada (grupo-Ag; controle). A L-arginina ou a água foi administrada diariamente por gavagem. Aos 15 dias de idade, os animais dos grupos Ar e Ag foram subdivididos de acordo com a condição de exercício físico a que foram submetidos: exercitados em esteira (grupo E) e não exercitado (grupo N). O exercício foi realizado em esteira (ET 2000 Insight) cinco dias por semana com duração diária de 30 minutos. Os grupos foram assim distribuídos (n = 6): AgN, AgE, ArN e ArE. Ao atingirem a idade de 35-45 dias de vida, os animais foram pesados, sacrificados e retidado o músculo gastrocnêmio. Este foi medido, pesado e processado para análise histológica. As imagens do músculo foram capturadas na objetiva de 100x para cálculo do diâmetro médio da fibra muscular. Os dados foram expressos na forma de média ± desvio padrão, analisados através do programa SPSS. Foram utilizados os testes de Shapiro-Wilk, ANOVA one way e teste de Tukey (p < 0,05). RESULTADOS: Não houve diferença entre os grupos, quanto ao peso corporal do animal e ao peso do músculo gastrocnêmio. No entanto, o grupo ArN apresentou diâmetro médio maior significativamente quando comparado aos dos demais grupos. CONCLUSÃO: Isto sugere que a L-arginina, em animais que não realizaram o exercício físico, promove hipertrofia muscular, enquanto que o exercício realizado não foi capaz de promover aumento do diâmetro da fibra muscular.

INTRODUCTION: Exercise and amino acid L-Arginine can promote anatomical and physiological changes in skeletal muscle. OBJECTIVE: The objective of this work was to analise the influence of L-arginine associated with the exercise in skeletal muscle fibers. METHODS: To carry out our research, 24 male Wistar rats divided into 4 groups according to the administration of Arginine and physical exercise wer used. The experimental groups were distributed as follows: Arginine-Exercise (AE, n = 6), Arginine-Not Exercised (AN, n = 6), Water-Exercise (WE, n = 6) and Water-Not Exercised (WN, n = 6). The amino acid L-Arginine was administered via orogastric intubation, at dose of 300mg/kg, daily from the 7th to 35th days of life of the animal. The exercise was performed on motorized treadmill for 30 minutes/day, 5 times a week, from 15th to 35th days of life of the animal. At the age of 35-45 days, the animals were weighed and sacrificed in order to collect the gastrocnemius muscle. The gastrocnemius muscle was measured, weighed and processed for histological analysis. The muscle's images were taken in order to calculate the mean diameter of the muscle fiber. Data were expressed as mean ± standard deviation and analyzed using SPSS. The Shapiro-Wilk, one-way ANOVA and Tukey's tests (p <0.05) were applied. RESULTS: Concerning body weight and gastrocnemius weight, there was no significant difference when all the experimental groups were compared. However, the AN group presented the highest mean diameter when compared to the other groups. CONCLUSION: This fact suggests that orogastric administration of Arginine offered to the animals that were not exercised, promotes muscle hypertrophy. On the other hand, exercise by itself did not lead to increase in mean diameter of skeletal muscle.

Differential effects of physical exercise and L-arginine on cortical spreading depression in developing rats.

OBJECTIVE: We investigated the effect of early-in-life administration of L-arginine, combined with physical exercise, on cortical spreading depression (CSD) in young and adult rats. METHODS: L-arginine (300 mg/kg/day, n = 40) or distilled water (vehicle, n = 40) was given to the rats during postnatal days 7-35 by gavage. Physical exercise (treadmill) was carried out during postnatal days 15-35 in half of the animals in each gavage condition described above. The other half (non-exercised) was used for comparison. When the animals reached 35-45 days (young groups) or 90-120 days of age (adult) CSD was recorded on two cortical points during 4 hours and CSD propagation velocity was calculated. RESULTS: L-arginine-treated + exercised rats had increased body weight, but not brain weight, in adult age compared to L-arginine + non-exercised ones (P < 0.05). In both young and adult animals, L-arginine increased, whereas exercise decreased the CSD propagation velocity. Analysis of variance revealed a significant interaction between gavage treatment and age (P < 0.001), and also between gavage treatment and exercise (P = 0.004), but not between age and exercise. An additional control group of young rats, treated with 300 mg/kg of L-histidine, presented CSD velocities comparable to the corresponding water-treated controls, suggesting that the CSD acceleration seen in the L-arginine group was an L-arginine-specific effect, rather than an effect due to a non-specific amino acid imbalance. DISCUSSION: L-arginine and exercise affect CSD differentially (L-arginine accelerated, while exercise decelerated CSD), and both effects did interact. Probably, they depend on developmental plasticity changes associated with the treatments.