Department of Neurology and the Peritz and Chantal Scheinberg Cerebrovascular Research Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
J Mol Neurosci. 2012 May;47(1):166-72. doi: 10.1007/s12031-012-9706-8. Epub 2012 Jan 13.
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.
成纤维细胞生长因子 2（FGF2）和血管内皮生长因子（VEGF）是内源性神经干细胞（eNSC）的有效有丝分裂原，也能诱导血管生成。我们在创伤性脑损伤（TBI）后 7 天通过侧脑室输注这些因子或其组合，以评估其对功能结果以及 eNSC 增殖和分化的影响。结果表明，VEGF 诱导侧脑室下区和损伤皮层周围增殖的 eNSC 数量显著增加，而 FGF2 和 VEGF 的组合并未增强 VEGF 的单独作用。命运分析表明，大多数新生细胞分化为星形胶质细胞和少突胶质细胞，而只有少数细胞分化为神经元。与载体相比，用 VEGF、FGF2 或其组合治疗的小鼠功能结果明显更好。只有用 VEGF 治疗的小鼠损伤体积显著减小，表明 VEGF 具有额外的神经保护作用。联合治疗对结果或神经元分化没有相加作用。总之，与单独使用因子相比，FGF2-VEGF 联合治疗不能增加 TBI 后的神经发生和血管生成或减少损伤体积。这可能表明大脑再生存在上限效应。
