RESUMO
PURPOSE: Cerebral ischemia is the result of decreased or interrupted blood flow to the brain. It is the third leading cause of death after cardiovascular disease and cancer. Cerebral ischemia is reversible or irreversible in neurons in the affected area, and subsequent free radical damage can be exacerbated if reperfusion occurs. Ciproxifan is used to study the involvement of histaminergic neurons in different phases such as wakefulness and cognition. We wanted to find out whether ciproxifan has a protective effect on the brain of rats with cerebral ischemia-reperfusion injury. MATERIALS AND METHODS: A total of 64 adult rats (32 male and 32 female) were used for the experiment. Eight cages were formed with randomly selected rats. No substance was administered to the rats in Group 1 and no surgical procedure was performed. The cerebral ischemia-reperfusion model (clamping of the left common carotid artery for 15 min followed by reperfusion for 24 h) was applied to rats in Group 2, Group 3, and Group 4 after 7 days/single dose of saline and ciproxifan (10 mg/kg, 30 mg/kg). After that, the activitymeter, forced swim test (FST), and Morris water maze (MWM) were performed on all animals. RESULTS: Rats treated with ciproxifan exhibit neurons and glial cells with histologic structures similar to those of the control group, and interestingly, these differences became more pronounced with increasing dose. Rats administered ciproxifan improved motor coordination, decreased total distance behavior, and improved learning ability. However, when the groups were compared by sex, no significant difference was found in the parameters. CONCLUSION: Thus, we could conclude that ciproxifan has a protective effect on the brain to a certain extent, regardless of the dose.
Cerebral ischemia is one of the leading causes of death.Cerebral ischemia is a common mechanism of acute brain injury that results from impaired blood flow to the brain.Ciproxifan is a well-investigated histamine H3 receptor inverse agonist/antagonist.Ciproxifan presynaptically inhibits glutamate release in rat hippocampus.
RESUMO
Unbalanced nutrition during perinatal period causes varying degrees of perturbations in the metabolism and cognitive functions of offspring. The aim of this study was to investigate effects of maternal and postweaning high-fat diet (HFD) exposure on the growth parameters, hippocampal functions and morphology of offspring in a sex-dependent manner. Spraque-Dawley rats were fed either standard (10 % fat) or saturated-fat (65 % fat) diet during their gestation and lactation period. After weaning, pups were sustained in same diet for 6 more weeks. Body mass index (BMI) of pups were monitored weekly, then spontaneous locomotor activities were recorded. Spatial learning and memory functions were analyzed by Morris Water Maze (MWM) test. Total volumetric changes of hippocampal subfields were estimated by Cavalieri method. HFD exposure produced sex-dependent alterations in BMI, serum lipid and activity levels. MWM results showed no significant difference among groups. However, retrieval indexes were higher in HFD-fed males. Total volumetric analysis of the dentate gyrus was comparable, but the pyramidal cell layer volume of HFD-fed males was lower than those of SD-fed males. Despite alterations in some growth and lipid parameters, maternal and perinatal exposure to HFD did not markedly affect cognitive functions and hippocampal morphology of offspring.
La nutrición desequilibrada durante el período perinatal causa diversos grados de perturbaciones en el metabolismo y las funciones cognitivas en neonatos. El objetivo de este estudio fue investigar los efectos de la exposición a una dieta alta en grasas (HFD) materna y posdestete en los parámetros de crecimiento, las funciones del hipocampo y la morfología de neonatos de una manera dependiente del sexo. Ratas SpragueDawley fueron alimentadas con dieta estándar (10 % grasa) o grasa saturada (65 % grasa) durante su período de gestación y lactancia. Después del destete, las crías se mantuvieron en la misma dieta durante 6 semanas. El índice de masa corporal (IMC) de las crías se controló semanalmente, luego se registraron las actividades locomotoras espontáneas. El aprendizaje espacial y las funciones de memoria se analizaron mediante la prueba Morris Water Maze (MWM). Los cambios volumétricos totales de los subcampos del hipocampo se estimaron mediante el método de Cavalieri. La exposición a HFD produjo alteraciones dependientes del sexo en el IMC, los niveles de lípidos séricos y los niveles de actividad. Los resultados de MWM no mostraron diferencias significativas entre los grupos. Sin embargo, los índices de recuperación fueron más altos en machos alimentados con HFD. El análisis volumétrico total del giro dentado fue comparable, pero el volumen de la capa de células piramidales de los machos alimentados con HFD fue menor que el de los machos alimentados con SD. A pesar de las alteraciones en algunos parámetros lipídicos y de crecimiento, la exposición materna y perinatal a HFD no afectó marcadamente las funciones cognitivas y la morfología del hipocampo de la descendencia.
Assuntos
Animais , Masculino , Feminino , Gravidez , Ratos , Efeitos Tardios da Exposição Pré-Natal , Gorduras na Dieta/efeitos adversos , Hipocampo/fisiopatologia , Hipocampo/patologia , Tamanho do Órgão , Ratos Sprague-Dawley , Aprendizagem em Labirinto , Fenômenos Fisiológicos da Nutrição Pré-Natal , Animais Recém-NascidosRESUMO
The aim of this study was to examine the effect of simvastatin (SMV), a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor, in rats fed with a standard or a high-fat diet (HFD) throughout the prenatal and the postnatal periods. The emotional status of the animals was evaluated by elevated plus-maze and modified forced swimming tests, whereas cognitive performance was assessed by a Morris water maze task. Morphological changes in the hippocampus were examined by design-based stereology. HFD exposure significantly increased blood serum triglycerides without altering cholesterol levels relative to the controls. After four weeks of oral SMV (5 mg/kg) administration, serum triglycerides reverted to the control level. SMV caused significant anxiolytic, antidepressant-like, and nootropic effects in animals fed the standard diet. In the HFD group, enhanced anxiety and depression, and reduced cognitive performances of animals were reversed by SMV treatment. Although a total volume estimation of the hippocampal subfields indicated no significant change among the groups, the total number of pyramidal neurons decreased significantly in animals fed the HFD; following SMV treatment, this detrimental effect was reversed. In conclusion, chronic SMV administration has significant therapeutic potential for the treatment of affective and cognitive disorders with or without altering the serum lipid profiles.
