Fate of newborn dentate granule cells after early life status epilepticus.
OBJECTIVE
To determine the fate of newborn dentate granule cells (DGCs) after lithium-pilocarpine-induced status epilepticus (SE) in an immature rat.


METHODS
Postnatal day 20 (P20) rats were injected with lithium and pilocarpine to induce SE, and then with bromodeoxyuridine (BrdU) 4, 6, and 8 days later (P24, 26, and 28), and killed 1 day (P29), 1 week (P34), and 3 weeks (P50) after the last dose of BrdU for cell counts. Immunohistochemistry and TUNEL staining were performed to assess the fate of newborn DGCs.


RESULTS
Pilocarpine-treated animals had significantly more BrdU-labeled DGCs than did littermate controls at all times. The day after the final BrdU injection (P29), sixfold more cells were found in pilocarpine-treated animals than in controls, which was reduced to threefold, 3 weeks later. A decrease in the BrdU-labeled cell density was noted from P29 to P50 in the control and pilocarpine-treated animals. Evidence of DGC cell death was seen in pilocarpine and control animals, with threefold more TUNEL-positive cells in the pilocarpine-treated than in the control animals at P29. The surviving newborn DGCs became mature neurons; expressing the neuronal marker NeuN in both control and pilocarpine-treated animals.


CONCLUSIONS
These findings suggest that SE during postnatal development increases the birth and death of DGCs. A subset of the newborn DGCs survive and mature into dentate granule neurons, resulting in an increased population of immature DGCs after SE that may affect hippocampal physiology.
Porter
Brenda E
BE
Division of Pediatric Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. Porterb@email.chop.edu
Maronski
Margaret
M
Brooks-Kayal
Amy R
AR
D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000379:methods; D018891:Dentate Gyrus / Q000254:growth & development* / Q000473:pathology*; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology*
D010862:Pilocarpine