Reduced neurogenesis after neonatal seizures

Bridget K. McCabe, Diosely C. Silveira, Maria Roberta Cilio, Byung Ho Cha, Xianzeng Liu, Yoshimi Sogawa, Gregory L. Holmes

Research output: Contribution to journalArticlepeer-review

Abstract

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 nonetheless clear indications that seizures may have other potentially deleterious effects. Because it is known that seizures in the mature brain can increase neurogenesis in the hippocampus, we studied the extent of neurogenesis in the granule cell layer of the dentate gyrus over multiple time points after a series of 25 flurothyl-induced seizures administered between postnatal day 0 (P0) and P4. Rats with neonatal seizures had a significant reduction in the number of the thymidine analog 5-bromo-2′deoxyuridine-5′-monophosphate- (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 after the BrdU injections. The reduction in BrdU-labeled cells continued for 6 d after the last seizure. BrdU-labeled cells primarily colocalized with the neuronal marker neuron-specific nuclear protein and rarely colocalized with the glial cell marker glial fibrillary acidic protein, providing evidence that a very large percentage of the newly formed cells were neurons. Immature rats subjected to a single seizure did not differ from controls in number of BrdU-labeled cells. In comparison, adult rats undergoing a series of 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.

Original languageEnglish (US)
Pages (from-to)2094-2103
Number of pages10
JournalJournal of Neuroscience
Volume21
Issue number6
DOIs
StatePublished - Mar 15 2001
Externally publishedYes

Keywords

  • Bromodeoxyuridine
  • Dentate gyrus
  • Epilepsy
  • Glial fibrillary acidic protein
  • Hippocampus
  • Neurogenesis
  • Neuron-specific nuclear protein
  • Seizures

ASJC Scopus subject areas

  • General Neuroscience

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