Reduced neurogenesis after neonatal seizures

Although neonatal seizures are quite common, there is controversy regarding their consequences. Despite considerable evidence that seizures may cause less cell loss in young animals compared with mature animals, there are non etheless clear indications that seizures may have other potentially deleter ious effects. Because it is known that seizures in the mature brain can inc rease neurogenesis in the hippocampus, we studied the extent of neurogenesi s in the granule cell layer of the dentate gyrus over multiple time points after a series of 25 flurothyl-induced seizures administered between postna tal day 0 (P0) and P4. Rats with neonatal seizures had a significant reduct ion in the number of the thymidine analog 5-bromo-2'-deoxyuridine- 5'-monop hosphate- (BrdU) labeled cells in the dentate gyrus and hilus compared with the control groups when the animals were killed either 36 hr or 2 weeks af ter the BrdU injections. The reduction in BrdU-labeled cells continued for 6 d after the last seizure. BrdU-labeled cells primarily colocalized with t he neuronal marker neuron-specific nuclear protein and rarely colocalized w ith the glial cell marker glial fibrillary acidic protein, providing eviden ce that a very large percentage of the newly formed cells were neurons. Imm ature rats subjected to a single seizure did not differ from controls in nu mber of BrdU-labeled cells. In comparison, adult rats undergoing a series o f 25 flurothyl-induced seizures had a significant increase in neurogenesis compared with controls. This study indicates that, after recurrent seizures in the neonatal rat, there is a reduction in newly born granule cells.