Malnutrition increases dentate granule cell proliferation in immature rats after status epilepticus

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 flurothyl 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.