Vascular Endothelial Growth Factors A and C are Induced in the SVZ Following Neonatal Hypoxia-Ischemia and Exert Different Effects on Neonatal Glial Progenitors

被引:48
作者
Bain, Jennifer M. [1 ,2 ,3 ]
Moore, Lisamarie [1 ,2 ,3 ]
Ren, Zhihua [1 ,2 ,3 ]
Simonishvili, Sophia [1 ,2 ,3 ]
Levison, Steven W. [1 ,2 ,3 ,4 ]
机构
[1] UMDNJ New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ 07103 USA
[2] UMDNJ Grad Sch Biomed Sci, Newark, NJ 07103 USA
[3] Univ Med & Dent New Jersey, New Jersey Med Sch, Univ Hosp Canc Ctr, Newark, NJ 07103 USA
[4] NJMS UH Canc Ctr, Dept Neurol & Neurosci, Newark, NJ 07103 USA
关键词
Neonatal hypoxia-ischemia; Subventricular zone; Glial progenitor; Oligodendrocyte; Astrocyte; Vascular endothelial growth factor; Cytokine; NEURAL STEM-CELLS; MOUSE SUBVENTRICULAR ZONE; BRAIN-DAMAGE; IN-VITRO; PERIVENTRICULAR LEUKOMALACIA; OLIGODENDROCYTE PROGENITORS; STIMULATES NEUROGENESIS; REACTIVE ASTROCYTES; NITRIC-OXIDE; ADULT BRAIN;
D O I
10.1007/s12975-012-0213-6
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Episodes of neonatal hypoxia-ischemia (H-I) are strongly associated with cerebral palsy and a wide spectrum of other neurological deficits in children. Two key processes required to repair damaged organs are to amplify the number of precursors capable of regenerating damaged cells and to direct their differentiation towards the cell types that need to be replaced. Since hypoxia induces vascular endothelial growth factor (VEGF) production, it is logical to predict that VEGFs are key mediators of tissue repair after H-I injury. The goal of this study was to test the hypothesis that certain VEGF isoforms increase during recovery from neonatal H-I and that they would differentially affect the proliferation and differentiation of subventricular zone (SVZ) progenitors. During the acute recovery period from H-I, both VEGF-A and VEGF-C were transiently induced in the SVZ, which correlated with an increase in SVZ blood vessel diameter. These growth factors were produced by glial progenitors, astrocytes, and to a lesser extent, microglia. VEGF-A promoted the production of astrocytes from SVZ glial progenitors, while VEGF-C stimulated the proliferation of both early and late oligodendrocyte progenitor cells (OPCs), which was abolished by blocking VEGFR-3. Altogether, these results provide new insights into the signals that coordinate the reactive responses of the progenitors in the SVZ to neonatal H-I. Our studies further suggest that therapeutics that can extend VEGF-C production and/or agonists that stimulate VEGFR-3 will promote OPC development to enhance myelination after perinatal brain injury.
引用
收藏
页码:158 / 170
页数:13
相关论文
共 50 条
[41]  
2-S
[42]   REGIONAL CEREBRAL BLOOD-FLOW DURING HYPOXIA-ISCHEMIA IN IMMATURE RATS [J].
VANNUCCI, RC ;
LYONS, DT ;
VASTA, F .
STROKE, 1988, 19 (02) :245-250
[43]  
Vannucci RC, 1999, J NEUROSCI RES, V55, P158, DOI 10.1002/(SICI)1097-4547(19990115)55:2<158::AID-JNR3>3.3.CO
[44]  
2-T
[45]   A model of perinatal hypoxic-ischemic brain damage [J].
Vannucci, RC ;
Vannucci, SJ .
FRONTIERS OF NEUROLOGY: A SYMPOSIUM IN HONOR OF FRED PLUM, 1997, 835 :234-249
[46]  
VANNUCCI RC, 1997, NEONATAL PERINATAL M, V4, P877
[47]   Vascular endothelial growth factor directly inhibits primitive neural stem cell survival but promotes definitive neural stem cell survival [J].
Wada, Tamaki ;
Haigh, Jody J. ;
Ema, Masatsugu ;
Hitoshi, Seiji ;
Chaddah, Radha ;
Rossant, Janet ;
Nagy, Andras ;
van der Kooy, Derek .
JOURNAL OF NEUROSCIENCE, 2006, 26 (25) :6803-6812
[48]   An improved method for propagating oligodendrocyte progenitors in vitro [J].
Young, GM ;
Levison, SW .
JOURNAL OF NEUROSCIENCE METHODS, 1997, 77 (02) :163-168
[49]   Neuroprotective role of vascular endothelial growth factor: Signalling mechanisms, biological function, and therapeutic potential [J].
Zachary, I .
NEUROSIGNALS, 2005, 14 (05) :207-221
[50]   Vascular endothelial growth factor promotes proliferation of cortical neuron precursors by regulating E2F expression [J].
Zhu, YH ;
Jin, KL ;
Mao, XO ;
Greenberg, DA .
FASEB JOURNAL, 2003, 17 (02) :186-193