Malnutrition Increases Dentate Granule Cell Proliferation in Immature Rats After Status Epilepticus

Abstract

Summary:Purpose: Nutritional insults early in life have a profound and often permanent effect on the development of the central nervous system. A direct relationship between malnutrition and epilepsy has not been established; however, it is believed that inadequate nutrition may predispose the brain to seizures. This study was designed to determine whether neonatally malnourished rats are different from nourished rats in terms of flurothyl seizure susceptibility at postnatal day (P)15, in the behavioral manifestations of seizures, and in status epilepticus-induced hippocampal injury.Methods: Sprague-Dawley rat pups were maintained on a starvation regimen from P2 until P17. Age-matched control rats were not exposed to starvation. At P15, all animals were exposed to flurothyl-induced status epilepticus. At P17, the rats received a single injection of bromodeoxyuridine (50 mg/kg intraperitoneal) to determine the extent of genesis of new cells in the dentate gyrus. At P18, the rats were killed, and the brains were processed for histology and immunohistochemistry.Results: Preliminary analysis indicates that early malnutrition did not modify flurothyl seizure susceptibility or the behavioral manifestations of seizures at P15. Histological assessment did not reveal any evidence of hippocampal cell loss after status epilepticus in either group. Malnutrition per se induced an increase in the genesis of new cells in the anterior dentate granule cell layer. Although exposure to status epilepticus augmented the expression of new cells in the dentate gyrus in both groups, this expression was more pronounced in the malnourished group.Conclusions: The findings suggest that malnutrition early in life alters dentate plasticity but not the susceptibility to flurothy1 seizures. Although status epilepticus can increase the expression of new cells in the dentate gyrus in immature rats, malnutrition followed by status epilepticus further increases dentate granule cell proliferation. Key Words: EpilepsyMalnutrition-Plasticity-CNS development-Hippocampus-Dentate gyrus.Malnutrition is one of the most important health problems in developing and underdeveloped countries. Nutritional insults early in life have a profound and often permanent effect on the subsequent development of the central nervous system. Clinical studies indicate that malnourished children have more learning and behavioral problems than well-nourished children (1-3). In a cross-sectional study from a pediatric population residing in a governmental institution, there was a trend toward a greater number of epilepsy cases among malnourished children compared with controls (4). However, a direct relationship between malnutrition and epilepsy has not been established in clinical studies.Many animal studies suggest that malnutrition may have detrimental effects on the brain and predispose the A decrease in the number of dendritic spines of pyramidal neurons of lamina I11 or V of the anterior cingulate cortex and in the CA3 hippocampal region was also described (6,7). Furtherm...

Effects of early malnutrition and nutritional rehabilitation in rats

“…Wasterlain sugere que não é a desnutrição, mas sim a repetição de crises no cérebro, em períodos críticos do desenvolvimento, a responsável pela redução no número de células e peso cerebral 20 . Em estudo prévio 13 , utilizando ratos desnutridos precocemente, submetidos a estado de mal convulsivo em Figura 2 -O gráfico apresenta as diferenças de peso (± SEM) em relação ao sexo e à idade P15, sem reabilitação nutricional, observamos diminuição do tamanho cerebral de animais desnutridos quando comparados aos controles (observação não publicada). Os achados opostos observados em nosso primeiro estudo em P15 e no atual, em P30, podem estar relacionados tanto ao efeito das crises em período em que ocorre extenso crescimento e diferenciação celular (idade P15) como ao efeito da reabilitação nutricional.…”

“…Após o período de privação nutricional, os filhotes retornavam para a sua gaiola com livre acesso à fêmea nutriz. Os animais controle permaneciam sempre em sua gaiola, com livre acesso à lactação 13 .…”

“…Entre os mais utilizados, encontram-se a restrição alimentar pelo afastamento da mãe durante o período de lactação, dietas hipoprotéicas e dietas deficientes em aminoácidos essenciais. O modelo experimental de desnutrição crônica precoce, por restrição da ingesta alimentar 13 , é o mais semelhante ao que acontece na nossa população infantil, a desnutrição protéico-calórica nos dois primeiros anos de vida, iniciando após o término do aleitamento materno.…”

“…A vantagem da utilização do método de inalação de flurothyl deve-se ao fato de as crises poderem ser moduladas e interrompidas rapidamente através de alterações no gotejo da droga 13 .…”

The influence of gestational age and birth weight in the clinical assesment of the muscle tone of healthy term and preterm newborns

“…About 70% t o 75% of newborns that are discharged from the intensive care units still present low to medium risk for problems in the neurological development and this ratio increases as the weight and gestational age decre a s e s 1 0 . Intrauterine malnutrition seems to influence central nervous system (CNS) maturation anatomically and functionally 11,12 . Newborns with low birth weight frequently show abnorm a l ities in their neurological outcome.…”