[Endogenous self-repair in immature white matter induced by ischemia in neonatal rats].
OBJECTIVE
To study in vivo the endogenous self-repair mechanism in immature white matter induced by ischemia in neonatal rats with periventricular leukomalacia (PVL).


METHODS
Five-day-old neonatal Sprague-Dawley (SD) rats were randomly divided into sham and PVL groups. Rat model of PVL was prepared by ligation of the right common carotid artery following 2 hours of exposure to 8% oxygen. Pathological changes and myelination in the white matter were assessed under light and electron microscopy at 7 and 21 days after PVL. O4-positive OL precursor cells in the white matter were determined with immunofluorescence staining. Activation, proliferation, migration and differentiation of glial progenitor cells in SVZ were observed using immunofluorescent double labeling of either NG2 (marker of progenitor cells) and 5-bromodeoxyuridine (BrdU), or O4 (marker of OL precursor cells) and BrdU.


RESULTS
All rats in the PVL group manifested either mild or severe white matter injury under light microscopy, and had higher pathological scores of white matter compared with the sham group at 7 and 21 days after PVL (P<0.05). Electron microscopy showed that the number and thickness of myelin sheath in the PVL group were significantly reduced compared with the sham group (P<0.01). O4-positive OL precursor cells in the white matter observed under fluorescence microscopy were significantly reduced in the PVL group compared with the sham group (P<0.05). BrdU/NG2-positive cells in the SVZ increased significantly in the PVL group 48 hours after PVL and migrated into the periventricular area, reaching a peak on day 7 after PVL. BrdU/O4-positive newborn cells began to appear in the periventricular area 72 hours after PVL, and the number of BrdU/O4-positive cells in the PVL group was statistically more than in the sham group on day 21 after PVL (P<0.05).


CONCLUSIONS
Ischemia may induce brain self-repair in neonatal rats, resulting in activation and proliferation of NG2 glial progenitor cells in the SVZ migration and differentiation into OL precursor cells in periventricular white matter.
Shanghai Institute for Pediatric Research, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Wen-Juan
WJ
Li
Hui-Jin
HJ
Chen
Long-Hua
LH
Qian
Feng-Xia
FX
Mao
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D007969:Leukomalacia, Periventricular / Q000473:pathology; D009186:Myelin Sheath / Q000502:physiology; D009457:Neuroglia / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000473:pathology
D001973:Bromodeoxyuridine