Temporal profile of neural stem cell proliferation in the subventricular zone after ischemia/hypoxia in the neonatal rat brain.
OBJECTIVE
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% O(2) and 92% N(2), at 33 degrees 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.


CONCLUSIONS
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.
Iwai
Masanori
M
Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, Okayama, 700-8558, Japan.
Ikeda
Tomoaki
T
Hayashi
Takeshi
T
Sato
Keiko
K
Nagata
Tetsuya
T
Nagano
Isao
I
Shoji
Mikio
M
Ikenoue
Tsuyomu
T
Abe
Koji
K
D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D007839:Functional Laterality; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000473:pathology*; D013997:Time Factors
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D001973:Bromodeoxyuridine