Protective effects of VEGF treatment on focal cerebral ischemia in rats

Zhang,Aimei; Liang,Lunan; Niu,Huanfu; Xu,Peng; Hao,Yongnan

doi:10.3892/mmr.2012.1069

Protective effects of VEGF treatment on focal cerebral ischemia in rats

Authors:
- Aimei Zhang
- Lunan Liang
- Huanfu Niu
- Peng Xu
- Yongnan Hao
View Affiliations

Affiliations: The Affiliated Hospital of Jining Medical College, Jining, Shandong 272029, P.R. China
Published online on: September 10, 2012 https://doi.org/10.3892/mmr.2012.1069
Pages: 1315-1318

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of this study was to determine the effects of VEGF treatment on focal cerebral ischemia in rats. Rats were administered PBS or VEGF at concentrations of 10, 20 or 30 µg/ml. The effects of VEGF on the rat infarct volume and neurological deficits were investigated. Transmission electron microscopy was used to observe the ultrastructure of the cerebral cortex. Treatments with VEGF reduced the infarct volume and improved neurological functions. VEGF increased microvessel generation and also inhibited apoptosis in the cerebral cortex and basal ganglia. For the rats in the 30 µg/ml VEGF group, an even higher number of proliferative endothelial cells were observed by electron microscopy. In conclusion, VEGF treatment has protective effects on focal cerebral ischemia in rats.

View Figures

View References

1	Chen XL, Nam JO, Jean C, et al: VEGF-induced vascular permeability is mediated by FAK. Dev Cell. 22:146–157. 2012. View Article : Google Scholar : PubMed/NCBI
2	Weis SM: Evaluation of VEGF-induced vascular permeability in mice. Methods Mol Biol. 763:403–415. 2011. View Article : Google Scholar : PubMed/NCBI
3	Nassehi D, Dyrbye H, Andresen M, Thomsen C, Juhler M, Laursen H and Broholm H: Vascular endothelial growth factor A protein level and gene expression in intracranial meningiomas with brain edema. APMIS. 119:831–843. 2011. View Article : Google Scholar : PubMed/NCBI
4	Schmid S, Aboul-Enein F, Pfisterer W, Birkner T, Stadek C and Knosp E: Vascular endothelial growth factor: the major factor for tumor neovascularization and edema formation in meningioma patients. Neurosurgery. 67:1703–1708. 2010. View Article : Google Scholar : PubMed/NCBI
5	Krupinski J, Kaluza J, Kumar P, Kumar S and Wang JM: Role of angiogenesis in patients with cerebral ischemic stroke. Stroke. 25:1794–1798. 1994. View Article : Google Scholar : PubMed/NCBI
6	Zan LK, Song YJ, Teng GX, et al: Expression and function of vascular endothelial growth factor and angiopoietins in rat brain after cerebral ischemia. Chin J Pathol. 40:834–839. 2011.(In Chinese).
7	Ma Y, Qu Y and Fei Z: Vascular endothelial growth factor in cerebral ischemia. J Neurosci Res. 89:969–978. 2011. View Article : Google Scholar : PubMed/NCBI
8	Longa EZ, Weinstein PR, Carlson S and Cummins R: Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 20:84–91. 1989. View Article : Google Scholar : PubMed/NCBI
9	Sondell M, Lundborg G and Kanje M: Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous systerm. J Neurosci. 19:5731–5740. 1999.
10	Silverman WF, Krum JM, Mani N and Rosenstein JM: Vascular, glial and neuronal effects of vascular endothelial growth factor in mesencephalic explant cultures. Neuroscience. 90:1529–1541. 1999. View Article : Google Scholar : PubMed/NCBI
11	Ku DD, Zaleski JK, Liu S and Brock TA: VEGF induces EDRF-dependent relaxation in coronary arteries. Am J Physiol. 265:H586–H592. 1993.PubMed/NCBI
12	Marti HJ, Bernaudin M, Bellail A, Schoch H, Euler M, Petit E and Risau W: Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. Am J Pathol. 156:965–976. 2000. View Article : Google Scholar
13	Jin KL, Mao XO and Greenberg DA: Vascular endothelial growth factor: director neuroprotective effect in in vitro ishemia. Proc Natl Acad Sci USA. 97:10242–10247. 2000. View Article : Google Scholar : PubMed/NCBI
14	Jin KL, Mao XO, Nagayama T, Goldsmith PC and Greenberg DA: Induction of vascular endothelial growth factor receptors and phosphatidylinositol 3′-kinase/Akt signaling by global cerebral ischemia in the rat. Neuroscience. 100:713–717. 2000.
15	Hayashi T, Abe K and Itoyama Y: Reduction of ischemic damage by application of vascular endothelial growth factor in rat brain after transient ischemia. J Cereb Blood Flow Metab. 18:887–895. 1998. View Article : Google Scholar : PubMed/NCBI
16	Zhang ZG, Zhang L, Jiang Q, et al: VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest. 106:829–838. 2000. View Article : Google Scholar : PubMed/NCBI
17	Mayhan W: VEGF increases permeability of the blood-brain barrier via a nitric oxide synthase/CGMP-dependent pathway. Am J Physiol. 276:C1148–C1153. 1999.PubMed/NCBI
18	Rosenstein JM, Mani N, Silverman WF and Krum JM: Patterns of brain angiogenesis after vascular endothelial growth factor administration in vitro and in vivo. Proc Natl Acad Sci USA. 95:7086–7091. 1998. View Article : Google Scholar : PubMed/NCBI
19	Proescholdt MA, Heiss JD, Walbridge S, Mühlhauser J, Capogrossi MC, Oldfield EH and Merrill MJ: VEGF modulates vascular permeability and inflammation in rat brain. J Neuropathol Exp Neurol. 58:613–627. 1999. View Article : Google Scholar : PubMed/NCBI
20	Harrigan MR, Ennis SR, Masada T and Keep RF: Intraventricular infusion of VEGF promotes cerebral angiogenesis with minimal brain edema. Neurosurgery. 50:589–598. 2002.PubMed/NCBI
21	Plate KH, Breier G, Millauer B, Ullrich A and Risau W: Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. Cancer Res. 53:5822–5827. 1993.PubMed/NCBI
22	Plate KH, Breier G, Weich HA, Mennel HD and Risau W: VEGF and glioma angiogenesis: Coordinate induction of VEGF receptors, distribution of VEGF protein and possible in vivo regulatory mechanisms. Int J Cancer. 59:520–529. 1994. View Article : Google Scholar : PubMed/NCBI
23	Furlan M, Marchal G, Viader F, Derlon JM and Baron JC: Spontaneous neurological recovery after stroke and the fate of the ischemic penumbra. Ann Neurol. 40:216–226. 1996. View Article : Google Scholar : PubMed/NCBI
24	Rosenblum WI: Histopathologic clues to the pathways of neuronal death following ischemia/hypoxia. J Neurotrauma. 14:313–326. 1997. View Article : Google Scholar : PubMed/NCBI
25	Pulera MR, Adams LM, Liu H, et al: Apoptosis in a neonatal rat model of cerebral hypoxia ischemia. Stroke. 29:2622–2630. 1998. View Article : Google Scholar : PubMed/NCBI
26	Beiharz EJ, Williams CE, Dragunow M, et al: Mechanisms of delayed cell death following hypoxic-ischemic injury in the immature rat: evidence for apoptosis during selective neuronal loss. Brain Res Mol Brain Res. 29:1–14. 1995. View Article : Google Scholar : PubMed/NCBI
27	Sei Y, Von Lubitz KJ, Basile AS, Borner MM, Lin RC, Skolnick P and Fossom LH: Internucleosomal DNA fragmentation in gerbil hippocampus following forebrain ischemia. Neurosci Lett. 171:179–182. 1994. View Article : Google Scholar : PubMed/NCBI
28	Linnik MD, Miller JA, Sprinkle-Cavallo J, Mason PJ, Thompson FY, Montgomery LR and Schroeder KK: Apoptotic DNA fragmentation in the rat cerebral cortex induced by permanent middle cerebral artery occlusion. Brain Res Mol Brain Res. 32:116–124. 1995. View Article : Google Scholar : PubMed/NCBI