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

• Published in: Journal of molecular neuroscience 2012-05, Vol.47 (1), p.166-172
• Main Authors: Thau-Zuchman, Orli, Shohami, Esther, Alexandrovich, Alexander G., Leker, Ronen R.
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Astrocytes; Biomedical and Life Sciences; Biomedicine; Brain Injuries - drug therapy; Brain Injuries - metabolism; Brain Injuries - pathology; Cell Biology; Cortex; Differentiation; Disease Models, Animal; Drug Therapy, Combination; Fibroblast growth factor 2; Fibroblast Growth Factor 2 - pharmacology; Fibroblasts; Male; Mice; Mice, Inbred Strains; Mitogens; Neonates; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Nerve Regeneration - drug effects; Nerve Regeneration - physiology; Nervous system; Neural stem cells; Neural Stem Cells - drug effects; Neural Stem Cells - physiology; Neurochemistry; Neurogenesis; Neurogenesis - drug effects; Neurogenesis - physiology; Neurology; Neuroprotection; Neuroprotective Agents - pharmacology; Neurosciences; Oligodendrocytes; Proteomics; Regeneration; Stem cells; subventricular zone; Traumatic brain injury; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - pharmacology; Ventricle (lateral)
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-012-9706-8

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.