Endogenous self-repair in immature white matter induced by ischemia in neonatal rats

LI Wen-Juan; CHEN Hui-Jin; QIAN Long-Hua; MAO Feng-Xia

PDF(2298 KB)

Chinese Journal of Contemporary Pediatrics ›› 2012, Vol. 14 ›› Issue (07) : 548-553.

Endogenous self-repair in immature white matter induced by ischemia in neonatal rats

LI Wen-Juan, CHEN Hui-Jin, QIAN Long-Hua, MAO Feng-Xia

Author information +

History +

Abstract

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.

Key words

Periventricular leukomalacia / NG2 progenitor cell / Neonatal rats

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

LI Wen-Juan, CHEN Hui-Jin, QIAN Long-Hua, MAO Feng-Xia. Endogenous self-repair in immature white matter induced by ischemia in neonatal rats[J]. Chinese Journal of Contemporary Pediatrics. 2012, 14(07): 548-553

References

［1］Khwaja O, Volpe JJ. Pathogenesis of cerebral white matter injury of prematurity［J］. Arch Dis Child Fetal Neonate Ed, 2008, 93(2): F153-F161.

［2］Tramontin AD, García-Verdugo JM, Lim DA, Alvarez-Buyllan A. Postnatal development of radial glia and the ventricular zone (VZ): a continuum of the neural stem cell compartment［J］. Cereb Cortex, 2003, 13(6): 580-587.

［3］Fagel DM, Ganat Y, Silbereis J, Ebbitt T, Stewart W, Zhang H, et al. Cortical neurogenesis enhanced by chronic perinatal hypoxia［J］. Exp Neurol, 2006, 199(1): 77-91.

［4］Decressac M, Prestoz L, Veran J, Cantereau A, Jaber M,Gaillard A. Neuropeptide Y stimulates proliferation, migration and differentiation of neural precursors from the subventricular zone inadult mice［J］. Neurobiol Dis, 2009, 34(3): 441-449.

［5］Curtis MA, Kam M, Nannmark U, Anderson MF, Axell MZ, Wikkelso C, et al. Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension［J］. Science, 2007, 315(5816): 1243-1249.

［6］李文娟，陈惠金. 脑内在修复潜能机制［J］. 中国当代儿科杂志，2011，13（7）：606-611.

［7］贺月秋，陈惠金，钱龙华，陈冠仪. 脑室周围白质软化新生大鼠模型的创建及所伴随的白内障病变［J］. 中国当代儿科杂志，2007，9（3）：220-224.

［8］贺月秋，陈惠金，钱龙华，陈冠仪. 不同缺血方式制作脑室周围白质软化大鼠模型的比较［J］. 实验动物与比较医学，2010，30（3）：153-157

［9］Uehara H, Yoshioka H, Kawase S, Nagai H, Ohmae T, Hasegawa K, et al. A new model of white matter injury in neonatal rats with bilateral carotid artery occlusion［J］. Brain Res, 1999, 837(1-2): 213-220.

［10］Back SA, Luo NL, Borenstein NS, Levine JM, Volpe JJ, Kinney HC. Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury［J］. J Neurosci, 2001, 21(4): 1302-1312.

［11］Tramontin AD, Garcia-Verdugo JM, Lim DA, Alarvez-Buylla A. Postnatal development of radial glia and the ventricular zone (VZ): a continuum of the neural stem cell compartment［J］. Cereb Cortex, 2003, 13(6): 580-587.

［12］Chandran S, Hunt D, Joannides A, Zhao C, Compston A, Franklin RJ. Myelin repair: the role of stem and precursor cells in multiple sclerosis［J］. Philos Trans R Soc Lond B Biol Sci, 2008, 363(1489): 117-183.

［13］贺月秋，陈惠金，钱龙华，陈冠仪. 不同缺氧时间制作新生大鼠脑室周围白质软化动物模型的比较［J］. 中国比较医学杂志，2009，19（12）：10-13.

［14］Munoz-Elias G, Woodbury D, Black IB. Marrow stromal cells, mitosis, and neuronal differentiation: stem cells and precursor functions［J］. Stem Cells, 2003, 21(4): 437-448.

［15］Kuhn HG, Cooper-Kuhn CM. Bromodeoxyuridine and the detection of neurogenesis［J］. Curr Pharm Biotechnol, 2007, 8(3): 127-131.

［16］Foster MT, Bartness TJ. Sympathetic but not sensory denervation stimulates white adipocyte proliferation［J］. Am J Physiol Regul Integr Comp Physiol, 2006, 291(6): R1630-R1637.

［17］Sypecka J, Sarnowska A, Domanska-Janik K. Crucial role of the local micro-environment in fate decision of neonatal rat NG2 progenitors［J］. Cell Prolif, 2009, 42(5): 661671.