OBJECTIVENeurogenesis in the dentate gyrus of hippocampus persists in brain of the immature and adult mammalian including human and it can be regulated by physiological and pathological events including nutritional status and seizures. The present study was designed to investigate the potential effects of malnutrition followed by status epileptics on hippocampal neurogenesis in the immature rat.

METHODSRat pups were divided into 4 groups: malnourished (M), nourished (N), malnourished plus seizures (MS) and nourished plus seizures (NS). The rat pups of group M and group MS were maintained on a starvation regimen from postnatal day 2 (P2) to P18. The status epilepticus of the rat pups in group MS and group NS was elicited by unilateral microinfusion of kainic acid (KA) into the amygdula at P15. Rat pups of the 4 groups were given bromodeoxyuridine (BrdU) intraperitoneally twice daily for 2 days beginning at P17. At P19, the rat pups were killed and the brains were processed for BrdU mitotic labeling combined with double-label immunohistochemistry using early neuron- or glia-specific markers TuJ1 (beta III tubulin) or GFAP (glial fibrillary acidic protein).

RESULTSThere were no significant differences in the latent time of seizure between group M and group N [(12.4 +/- 2.6) min vs. (12.1 +/- 2.9) min, P < 0.05]. Histological assessment did not reveal any evidence of hippocampal cell loss after status epilepticus in either group. BrdU-labeled cells were significantly higher in the rats of group MS (374 +/- 18) than group M (303 +/- 20), group NS (312 +/- 24) than group N (269 +/- 18), respectively (P < 0.01). There was also significant difference between group M and group N, group MS and group NS, respectively (P < 0.01). No significant difference was seen between the rats of group NS and group M (P > 0.05). Approximately 60% of BrdU-labeled cells coexpressed TuJ1, and 5% approximately 10% of those co-expressed GFAP.

CONCLUSIONEarly malnutrition do not alter KA seizure susceptibility and the behavioral manifestations of seizures at P15. Although malnutrition and status epilepticus can increase the proliferation of newly developed cells in the immature rat respectively, malnutrition followed by status epilepticus further increases this proliferation. Furthermore, most of newly developed cells differentiate into early neurons.