Abstracts

Nutritional insults early in life have a profound and often permanent effect on the development of the central nervous system. The direct relationship between malnutrition and epilepsy is not known. There is evidence that malnutrition could contribute to the raised prevalence of epilepsy in children in the developing world. In this study, we ascertained if malnutrition has an influence on seizure susceptibility and injury during early development.
Malnutrition was induced from postnatal day (P) 2 to 19, by separating rat pups from the mother. Age match control rats were not exposed to this regimen. During the study, immunochemistry was performed to determine the neurogenesis. Bromodeoxyuridine (BrdU), which labels proliferating cells, was injected on P10, P15, P19, P20 and P25. Animals were sacrifized and brains were processed for immunohistochemistry 36 hr after the injection.On P20, a group of rat pups was subjected to status epilepticus (SE) by lithium-pilocarpine injection (P20). Another group of rats received only saline(sham SE). Following the SE, BrdU was injected either on P20 or P25. Malnourished and control rats which did not receive BrdU injection were sacrificed on P38 to determine cell loss and axonal sprouting.
The animals tolerated the malnourished paradigm well. The malnourished animals were smaller and had developmental delay. The latency to seizure onset was shorter in the malnourished groups (13 minutes versus 21 minutes). [italic]Neurogenesis: [/italic]BrdU-labeled cells were confined to the hilar border of the granule cell layer of the dentate gyrus. The highest number of BrdU-labeled cells occurred in the animals injected at P10 and decreased until the last day the animals received BrdU (P25). Malnourished animals had fewer labeled cells than control animals at P15, P20 and P25 although significance was only reached for the P20 and P25. When BrdU was administered after the SE, both the control and malnourished rats had fewer labeled cells than the control that did not have SE . While number of BrdU-labeled cells was smaller in the malnourished group than the controls following SE, the findings were not statistically significant. [italic]Histology: [/italic]Rats with SE had modest cell loss in CA3, CA1, and the hilus. No difference in cell loss scores were found in the well nourished controls and malnourished rats. Pronounced sprouting of mossy fibers was observed in the supragranular region. In the supragranular region, rats subjected to malnutrition had significantly less sprouting than the controls (p=0.035).
Our findings suggest that malnutrition during brain development alters brain plasticity and seizure susceptibility. Malnourished rats had fewer new neurons than well nourished controls. SE reduced neurogenesis in both control and malnourished animals. The nutritional status of animals is an important factor in brain plasticity following SE and deserves further study.
[Supported by: A grant from the NINDS (NS27984)]