Combination of Vascular Endothelial and Fibroblast Growth Factor 2 for Induction of Neurogenesis and Angiogenesis after Traumatic Brain Injury

被引:44
作者
Thau-Zuchman, Orli [2 ,3 ,4 ]
Shohami, Esther [2 ]
Alexandrovich, Alexander G. [2 ]
Leker, Ronen R. [1 ,3 ,4 ]
机构
[1] Hadassah Univ Hosp, Dept Neurol, IL-91120 Jerusalem, Israel
[2] Hebrew Univ Jerusalem, Sch Pharm, Dept Pharmacol, IL-91120 Jerusalem, Israel
[3] Hadassah Hebrew Univ Med Ctr, Peritz & Chantal Scheinberg Cerebrovasc Res Lab, Jerusalem, Israel
[4] Hadassah Hebrew Univ Med Ctr, Dept Neurol, Jerusalem, Israel
关键词
Traumatic brain injury; Angiogenesis; Neurogenesis; Vascular endothelial growth factor; Fibroblast growth factor 2; Neuroprotection; CLOSED-HEAD INJURY; UP-REGULATION; VEGF; EXPRESSION; MICE; PERMEABILITY; REGENERATION; HIPPOCAMPUS; ASTROCYTES; CONTUSION;
D O I
10.1007/s12031-012-9706-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor (VEGF) are potent mitogens for endogenous neural stem cells (eNSC) and also induce angiogenesis. We infused the individual factors or their combination into the lateral ventricles of mice for 7 days after traumatic brain injury (TBI) in order to evaluate the effects on functional outcome and on eNSC proliferation and differentiation. The results show that VEGF induced a significant increment in the number of proliferating eNSC in the subventricular zone and in the perilesion cortex and that combination of FGF2 and VEGF did not augment the effects of VEGF alone. Fate analysis showed that most newborn cells differentiated into astrocytes and oligodendroglia while only a few cells differentiated into neurons. Functional outcome was significantly better in mice treated with VEGF, FGF2, or their combination as compared to vehicle. Injury size was significantly reduced only in mice treated with VEGF suggesting additional neuroprotective effects for VEGF. Combination therapy did not have an additive effect on outcome or neuronal differentiation. In conclusion, FGF2-VEGF combination does not augment neurogenesis and angiogenesis or reduce lesion volumes after TBI compared with individual factors. This may suggest the existence of a ceiling effect for brain regeneration.
引用
收藏
页码:166 / 172
页数:7
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