Impact of varying maternal dietary folate intake on cerebellar cortex histomorphology and cell density in offspring rats.

The cerebellum has a long, protracted developmental period that spans from the embryonic to postnatal periods; as a result, it is more sensitive to intrauterine and postnatal insults like nutritional deficiencies. Folate is crucial for foetal and early postnatal brain development; however, its effects on cerebellar growth and development are unknown. The aim of this study was to examine the effects of maternal folate intake on the histomorphology and cell density of the developing cerebellum. Twelve adult female rats (rattus norvegicus) were randomly assigned to one of four premixed diet groups: standard (2 mg/kg), folate-deficient (0 mg/kg), folate-supplemented (8 mg/kg) or folate supra-supplemented (40 mg/kg). The rats started their diets 14 days before mating and consumed them throughout pregnancy and lactation. On postnatal days 1, 7, 21 and 35, five pups from each group were sacrificed, and their brains were processed for light microscopic analysis. Histomorphology and cell density of the external granule, molecular, Purkinje and internal granule layers were obtained. The folate-deficient diet group had smaller, dysmorphic cells and significantly lower densities of external granule, molecular, Purkinje and internal granule cells. Although the folate-enriched groups had greater cell densities than the controls, the folate-supplemented group had considerably higher cell densities than the supra-supplemented group. The folate supra-supplemented group had ectopic Purkinje cells in the internal granule cell layer. These findings imply that a folate-deficient diet impairs cellular growth and reduces cell density in the cerebellar cortex. On the other hand, folate supplementation increases cell densities, but there appears to be an optimal dose of supplementation since excessive folate levels may be detrimental.

Maternal usage of varying levels of dietary folate affects the postnatal development of cerebellar folia and cortical layer volumes.

OBJECTIVE: The cerebellum has a long, protracted developmental period; therefore, it is more sensitive to intrauterine and postnatal insults like nutritional deficiencies. Folate is an essential nutrient in fetal and postnatal brain development, and its supplementation during pregnancy is widely recommended. This study aimed to describe the effects of maternal folate intake on postnatal cerebellum development. METHODS: Twelve adult female Rattus norwegicus (6-8 weeks old) rats were randomly assigned to one of four groups and given one of four premixed diets: a standard diet (2 mg/kg), a folate-deficient (folate 0 mg/kg), folate-supplemented (8 mg/kg), or folate supra-supplemented (40 mg/kg). The rats began consuming their specific diets 14 days before mating and were maintained on them throughout pregnancy and lactation. Five pups from each group were sacrificed, and their brains processed for light microscopic examination on postnatal days 1, 7, 21, and 35. The data gathered included the morphology of the cerebellar folia and an estimate of the volume of the cerebellar cortical layer using the Cavalieri method. RESULTS: Folia of the folate-supplemented and supra-supplemented groups were thicker and showed extensive branching with sub-lobule formation. The folate-deficient diet group's folia were smaller, had more inter-folial spaces, or fused. When compared to the folate-deficient group, the volumes of the cerebellum and individual cerebellar cortical layers were significantly larger in the folate-supplemented and supra-supplemented groups (p<0.05). CONCLUSION: Folate supplementation during pregnancy and lactation improves the degree and complexity of the cerebellar folia and the volumes of individual cerebellar cortical layers.

Age related effects of selective and non-selective COX-2 inhibitors on bone healing.

INTRODUCTION: Fractures are increasing worldwide and with an aging population, are frequent in the elderly. The healing of fractures progresses through various phases including the inflammatory stage. Aging is associated with slower healing and the use of non steroidal anti-inflammatory drugs (NSAIDs) may interrupt bone healing processes. We designed a study to compare the effect of diclofenac and celecoxib on fracture callus histomorphometry in a rat model of different age groups. METHODS: Using 5 and 15 month old rats, fractures were induced on the left tibia and the animals allocated to receive one of the drugs. Animals were sacrificed at day 21 and 42 and the fracture callus harvested for processing and histological evaluation. Tissue proportions and histological grades were determined and compared across the groups. RESULTS: Across all groups, the histological grade increased with time and animals in the young diclofenac group had the highest grade at day 42 (p = 0.004). The proportion of bone increased in all groups and was highest in the young diclofenac group at day 21 and day 42 (p = 0.003). Post hoc analysis showed that the young celecoxib and old celecoxib groups had the least proportion of bone (p = 0.032 and p = 0.003). The proportion of cartilage reduced in all groups at both time points. CONCLUSION: Celecoxib was associated with lower histological grade and lower proportion of bone in older animals. We urge for caution regarding the use of celecoxib in older people for the management of pain associated with fractures. Diclofenac may be a better option in this group.