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

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Abstract

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.

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Acknowledgments

This study was supported by the Sol Irwin Juni Trust Fund and by the Peritz and Chantal Scheinberg Cerebrovascular Research Fund

Disclosure and Conflict of Interest

All authors hereby declare they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Neurology and the Peritz and Chantal Scheinberg Cerebrovascular Research Laboratory, Hadassah–Hebrew University Medical Center, Jerusalem, Israel

    Orli Thau-Zuchman & Ronen R. Leker

  2. Department of Pharmacology, School of Pharmacy, The Hebrew University, Jerusalem, Israel

    Orli Thau-Zuchman, Esther Shohami & Alexander G. Alexandrovich

  3. Department of Neurology, Hadassah University Hospital, Ein Kerem, P. O. Box 12000, Jerusalem, 91120, Israel

    Ronen R. Leker

Authors
  1. Orli Thau-Zuchman
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  2. Esther Shohami
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  3. Alexander G. Alexandrovich
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  4. Ronen R. Leker
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Correspondence to Ronen R. Leker.

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Thau-Zuchman, O., Shohami, E., Alexandrovich, A.G. et al. Combination of Vascular Endothelial and Fibroblast Growth Factor 2 for Induction of Neurogenesis and Angiogenesis after Traumatic Brain Injury. J Mol Neurosci 47, 166–172 (2012). https://doi.org/10.1007/s12031-012-9706-8

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  • DOI: https://doi.org/10.1007/s12031-012-9706-8

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