Vascular Endothelial Growth Factor: an Attractive Target in the Treatment of Hypoxic/ischemic Brain Injury

Overview

Journal Neural Regen Res

Date 2016 Mar 17

PMID 26981109

Citations 27

Authors

Hui Guo

Hui Zhou

Jie Lu

Yi Qu

Dan Yu

Yu Tong

Affiliations

Soon will be listed here.

Abstract

Cerebral hypoxia or ischemia results in cell death and cerebral edema, as well as other cellular reactions such as angiogenesis and the reestablishment of functional microvasculature to promote recovery from brain injury. Vascular endothelial growth factor is expressed in the central nervous system after hypoxic/ischemic brain injury, and is involved in the process of brain repair via the regulation of angiogenesis, neurogenesis, neurite outgrowth, and cerebral edema, which all require vascular endothelial growth factor signaling. In this review, we focus on the role of the vascular endothelial growth factor signaling pathway in the response to hypoxic/ischemic brain injury, and discuss potential therapeutic interventions.

Citing Articles

Beyond vessels: unraveling the impact of VEGFs on neuronal functions and structure.

Aksan B, Mauceri D J Biomed Sci. 2025; 32(1):33.

PMID: 40050849 PMC: 11884128. DOI: 10.1186/s12929-025-01128-8.

Neuronutrition and Its Impact on Post-Stroke Neurorehabilitation: Modulating Plasticity Through Diet.

Ciancarelli I, Morone G, Iosa M, Cerasa A, Calabro R, Tozzi Ciancarelli M Nutrients. 2024; 16(21).

PMID: 39519537 PMC: 11547614. DOI: 10.3390/nu16213705.

Hydrogel in the Treatment of Traumatic Brain Injury.

Li S, Xu J, Qian Y, Zhang R Biomater Res. 2024; 28:0085.

PMID: 39328790 PMC: 11425593. DOI: 10.34133/bmr.0085.

Dysregulation of Plasma Growth Factors and Chemokines in Cocaine Use Disorder: Implications for Dual Diagnosis with Schizophrenia and Antisocial Personality Disorder in an Exploratory Study.

Torres-Galvan S, Flores-Lopez M, Ochoa E, Requena-Ocana N, Araos P, Herrera-Imbroda J Neuropsychobiology. 2024; 83(2):73-88.

PMID: 38768577 PMC: 11210571. DOI: 10.1159/000536265.

Hydrogen Sulfide Exerted a Pro-Angiogenic Role by Promoting the Phosphorylation of VEGFR2 at Tyr797 and Ser799 Sites in Hypoxia-Reoxygenation Injury.

Zhang S, Cheng Y, Guan Y, Wen J, Chen Z Int J Mol Sci. 2024; 25(8).

PMID: 38673925 PMC: 11050214. DOI: 10.3390/ijms25084340.

References

Mason J, Steinberg R, Lidington E, Kinderlerer A, Ohba M, Haskard D . Decay-accelerating factor induction on vascular endothelium by vascular endothelial growth factor (VEGF) is mediated via a VEGF receptor-2 (VEGF-R2)- and protein kinase C-alpha/epsilon (PKCalpha/epsilon)-dependent cytoprotective signaling pathway.... J Biol Chem. 2004; 279(40):41611-8. DOI: 10.1074/jbc.M407981200. View

Cheng X, Kuzuya M, Kim W, Song H, Hu L, Inoue A . Exercise training stimulates ischemia-induced neovascularization via phosphatidylinositol 3-kinase/Akt-dependent hypoxia-induced factor-1 alpha reactivation in mice of advanced age. Circulation. 2010; 122(7):707-16. PMC: 3071504. DOI: 10.1161/CIRCULATIONAHA.109.909218. View

Lai S, Johnson F . Defining the role of the JAK-STAT pathway in head and neck and thoracic malignancies: implications for future therapeutic approaches. Drug Resist Updat. 2010; 13(3):67-78. DOI: 10.1016/j.drup.2010.04.001. View

Baburamani A, Castillo-Melendez M, Walker D . VEGF expression and microvascular responses to severe transient hypoxia in the fetal sheep brain. Pediatr Res. 2012; 73(3):310-6. DOI: 10.1038/pr.2012.191. View

Coles J, Fryer T, Smielewski P, Chatfield D, Steiner L, Johnston A . Incidence and mechanisms of cerebral ischemia in early clinical head injury. J Cereb Blood Flow Metab. 2004; 24(2):202-11. DOI: 10.1097/01.WCB.0000103022.98348.24. View

Akiyama C, Yuguchi T, Nishio M, Tomishima T, Fujinaka T, Taniguchi M . Src family kinase inhibitor PP1 reduces secondary damage after spinal cord compression in rats. J Neurotrauma. 2004; 21(7):923-31. DOI: 10.1089/0897715041526230. View

Holzer L, Cor A, Pfandlsteiner G, Holzer G . Expression of VEGF, its receptors, and HIF-1α in Dupuytren's disease. Acta Orthop. 2013; 84(4):420-5. PMC: 3768045. DOI: 10.3109/17453674.2013.814011. View

Wang Z, Luo F, Li L, Yang L, Hu D, Ma X . STAT3 activation induced by Epstein-Barr virus latent membrane protein1 causes vascular endothelial growth factor expression and cellular invasiveness via JAK3 And ERK signaling. Eur J Cancer. 2010; 46(16):2996-3006. DOI: 10.1016/j.ejca.2010.07.008. View

Khaibullina A, Rosenstein J, Krum J . Vascular endothelial growth factor promotes neurite maturation in primary CNS neuronal cultures. Brain Res Dev Brain Res. 2004; 148(1):59-68. DOI: 10.1016/j.devbrainres.2003.09.022. View

10.

Shein N, Tsenter J, Alexandrovich A, Horowitz M, Shohami E . Akt phosphorylation is required for heat acclimation-induced neuroprotection. J Neurochem. 2007; 103(4):1523-9. DOI: 10.1111/j.1471-4159.2007.04862.x. View

11.

Moriyama Y, Takagi N, Hashimura K, Itokawa C, Tanonaka K . Intravenous injection of neural progenitor cells facilitates angiogenesis after cerebral ischemia. Brain Behav. 2013; 3(2):43-53. PMC: 3607146. DOI: 10.1002/brb3.113. View

12.

Kaur C, Ling E . Blood brain barrier in hypoxic-ischemic conditions. Curr Neurovasc Res. 2008; 5(1):71-81. DOI: 10.2174/156720208783565645. View

13.

Eliceiri B, Paul R, Schwartzberg P, Hood J, Leng J, Cheresh D . Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. Mol Cell. 2000; 4(6):915-24. DOI: 10.1016/s1097-2765(00)80221-x. View

14.

Dery M, Michaud M, Richard D . Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators. Int J Biochem Cell Biol. 2004; 37(3):535-40. DOI: 10.1016/j.biocel.2004.08.012. View

15.

Lin G, Bella A, Lue T, Lin C . Brain-derived neurotrophic factor (BDNF) acts primarily via the JAK/STAT pathway to promote neurite growth in the major pelvic ganglion of the rat: part 2. J Sex Med. 2006; 3(5):821-829. DOI: 10.1111/j.1743-6109.2006.00292.x. View

16.

Krum J, Mani N, Rosenstein J . Roles of the endogenous VEGF receptors flt-1 and flk-1 in astroglial and vascular remodeling after brain injury. Exp Neurol. 2008; 212(1):108-17. PMC: 2478519. DOI: 10.1016/j.expneurol.2008.03.019. View

17.

Rosell A, Morancho A, Navarro-Sobrino M, Martinez-Saez E, Hernandez-Guillamon M, Lope-Piedrafita S . Factors secreted by endothelial progenitor cells enhance neurorepair responses after cerebral ischemia in mice. PLoS One. 2013; 8(9):e73244. PMC: 3762828. DOI: 10.1371/journal.pone.0073244. View

18.

Fischer S, Wobben M, Marti H, Renz D, Schaper W . Hypoxia-induced hyperpermeability in brain microvessel endothelial cells involves VEGF-mediated changes in the expression of zonula occludens-1. Microvasc Res. 2001; 63(1):70-80. DOI: 10.1006/mvre.2001.2367. View

19.

Holmes K, Roberts O, Thomas A, Cross M . Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition. Cell Signal. 2007; 19(10):2003-12. DOI: 10.1016/j.cellsig.2007.05.013. View

20.

Hicklin D, Ellis L . Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2004; 23(5):1011-27. DOI: 10.1200/JCO.2005.06.081. View