Temporal profile of neural stem cell proliferation in the subventricular zone after ischemia/hypoxia in the neonatal rat brain

Masanori Iwai, Tomoaki Ikeda, Takeshi Hayashi, Keiko Sato, Tetsuya Nagata, Isao Nagano, Mikio Shoji, Tsuyomu Ikenoue, Koji Abe

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Objectives: Ischemia/hypoxia (I/H) causes severe neonatal brain injury, such as periventricular leukomaracia and hypoxic/ischemic encephalopathy. Neural stem cell research could lead to a treatment for such disorders. In order to elucidate the dynamic changes in neural stem cells in the neonatal brain after I/H, we investigated the proliferation of new cells in the subventricular zone (SVZ). Methods: Seven-day-old Wister rats were subjected to ligation of the left carotid artery followed by 2 hours of hypoxic stress (8% O2 and 92% N2, at 33°C). In order to elucidate the dynamic change of neural stem cells in the SVZ, single bromodeoxyuridine (BrdU; 50 mg/kg) was administered 2 hours before death 1, 7, 14 and 21 days after I/H. Immunohistochemical and immunofluorescent studies for BrdU and doublecortin (DCX) were carried out. As a control, a group of rats was subjected to sham surgery (incision of skin, but no ligation of the carotid artery) and no I/H. Results: The numbers of BrdU-labeled cells in the SVZ, for both the ipsilateral side and the contralateral side of the I/H brain, were twice the level of the control at 7 days after I/H, but the numbers for both sides returned to the control level at 21 days. In the ipsilateral side of the I/H brain, the number of BrdU-labeled cells in the SVZb (lining the upper wall of lateral ventricle) was 4-fold at 7 days and 15-fold at 21 days after I/H compared with the control level. This chronological pattern is very similar to the pattern for I/H results of the posterior periventricle (pPV). DCX appeared in most BrdU-labeled cells in the SVZb and pPV. Discussion: These findings indicate that I/H enhances neural stem cell proliferation in the SVZ, and some newborn cells migrate as neural precursors to the SVZb and pPV after I/H in the neonatal rat brain.

Original languageEnglish
Pages (from-to)461-468
Number of pages8
JournalNeurological Research
Volume28
Issue number4
DOIs
Publication statusPublished - Jun 2006

Keywords

  • Ischemia/hypoxia
  • Neonatal rat brain
  • Neural stem cells
  • Proliferation
  • Subventricular zone

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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