Hippocampal neurogenesis in developing rats induced by status epilepticus / 中华神经科杂志

ABSTRACT

Objective To observe neural stem cells proliferation,migration and differentiation in hippocampus in developing rats with status epileptictus.Methods 320 healthy SD rats at age 7,14,21,28 d (P7,P14,P21,P28) were randomly divided into status epilepticus (SE) and normal control group.In each group those rats at the same age were further randomly divided into 1,7,14,21,28 d five time points after PTZ-induced SE (n =8).New cell proliferation and migration were observed by immunohistochemistry studies in the dentate gyms.Double labeling with Brdu/NeuN and Brdu/GFAP was performed in the P14 rats.Results Nestin positive cells appeared in the dentate gyms on 1 d after SE in P7,P14,P21,P28 rats.The number of nestin positive cells gradually increased on 7 d and reached a peak on 14 d,then gradually reduced on 21 d,finally fell to a minimum on 28 d after SE.The numbers of nestin positive cells on 7 d(177.00 ± 3.22,t =16.033) and 14 d (195.00 ± 3.41,t =28.840) were significantly higher in the SE group than the NS group (147.50 ± 2.08,136.50 ± 2.65,both P ＜ 0.05).The smaller age of rats with SE onset,the greater the nestin intensity.But the number of nestin positive cells in the dentate gyrus of normal rats were gradually decreased with increasing age.Nestin positive cells were distributed in subgranular zone of dentate gyrus on 1 d and 7 d after SE,then gradually migrated to the granule cell layer on 14 d with morphological changes.Small part of nestin positive cells were ectopically migrated to the hilus of dentate gyrus in P14,P21,P28 age rats,and were also seen in the CA1,CA3 of hippocampus and cortex with various cell morphology.For differentiation of newly generated cells,most of Brdu positive cells coexpressed NeuN and about 4％-5％ cells co-expressed GFAP.Conclusions SE could induce neurogenesis in the hippocampal dentate gyrus area in developing rats which has age-related characteristics.Most new cells migrate from the subgranular zone to the granule cell layer of the dentate gyrus,and a small number of newly generated cells ectopically migrated to the hilus of dentate.The majority of newly generated cells differentiate into neurons,and the others differentiate into glial.