BrdU-positive cells in the neonatal mouse hippocampus following hypoxic-ischemic brain injury

John Bartley, Thomas Soltau, Hereward Wimborne, Sunjun Kim, Angeline Martin-Studdard, David C Hess, William D Hill, Jennifer L Waller, James Edwin Carroll

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Abstract

Background: Mechanisms that affect recovery from fetal and neonatal hypoxic-ischemic (H-I) brain injury have not been fully elucidated. The incidence of intrapartum asphyxia is approximately 2.5%, but the occurrence of adverse clinical outcome is much lower. One of the factors which may account for this relatively good outcome is the process of neurogenesis, which has been described in adult animals. We used a neonatal mouse model to assess new cells in the hippocampus after H-I injury. Results: Neonatal mice underwent permanent unilateral carotid ligation on the seventh postnatal day followed by exposure to 8% hypoxia for 75 minutes. The presence of new cells was determined by bromodeoxyuridine (BrdU) incorporation into cells with sacrifice of the animals at intervals. Brain sections were stained for BrdU in combination with neuronal, glial, endothelial and microglial stains. We found a significant increase in BrdU-positive cells in the neonatal mouse hippocampus in the injured area compared to the non-injured area, most prominent in the dentate gyrus (DG) (154.5 ± 59.6 v. 92.9 ± 32.7 at 3 days after injury; 68.9 ± 23.4 v. 52.4 ± 17.1 at 35 days after injury, p < 0.0011). Among the cells which showed differentiation, those which were stained as either microglial or endothelial cells showed a peak increase at three days after the injury in the DG, injured versus non-injured side (30.5 ± 17.8 v. 2.7 ± 2.6, p < 0.0002). As in the adult animal, neurogenesis was significantly increased in the DG with injury (15.0 ± 4.6 v. 5.2 ± 1.6 at 35 days after injury, p < 0.0002), and this increase was subsequent to the appearance of the other dividing cells. Numbers of new oligodendrocytes were significantly higher in the DG on the non-injured side (7.0 ± 24.2 v. 0.1 ± 0.3, p < 0.0002), suggesting that oligodendrocyte synthesis was reduced in the injured hippocampus. Conclusion: These findings demonstrate that the neonatal animal responds to brain injury with neurogenesis, much like the adult animal. In addition, H-I insult leads to more neurogenesis than hypoxia alone. This process may play a role in the recovery of the neonatal animal from H-I insult, and if so, enhancement of the process may improve recovery.

Original languageEnglish (US)
Article number15
JournalBMC Neuroscience
Volume6
DOIs
StatePublished - Mar 2 2005

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Bromodeoxyuridine
Brain Injuries
Hippocampus
Neurogenesis
Dentate Gyrus
Wounds and Injuries
Newborn Animals
Oligodendroglia
Asphyxia
Neuroglia
Ligation
Coloring Agents
Endothelial Cells
Incidence
Brain

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

Cite this

BrdU-positive cells in the neonatal mouse hippocampus following hypoxic-ischemic brain injury. / Bartley, John; Soltau, Thomas; Wimborne, Hereward; Kim, Sunjun; Martin-Studdard, Angeline; Hess, David C; Hill, William D; Waller, Jennifer L; Carroll, James Edwin.

In: BMC Neuroscience, Vol. 6, 15, 02.03.2005.

Research output: Contribution to journalArticle

Bartley, John ; Soltau, Thomas ; Wimborne, Hereward ; Kim, Sunjun ; Martin-Studdard, Angeline ; Hess, David C ; Hill, William D ; Waller, Jennifer L ; Carroll, James Edwin. / BrdU-positive cells in the neonatal mouse hippocampus following hypoxic-ischemic brain injury. In: BMC Neuroscience. 2005 ; Vol. 6.
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AU - Soltau, Thomas

AU - Wimborne, Hereward

AU - Kim, Sunjun

AU - Martin-Studdard, Angeline

AU - Hess, David C

AU - Hill, William D

AU - Waller, Jennifer L

AU - Carroll, James Edwin

PY - 2005/3/2

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