Abstract
Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of brain edema formation after experimental subarachnoid hemorrhage (SAH). In this study, we evaluated the effect of anti-VEGF antibody neutralization on brain edema formation after experimental SAH in mice. Mice underwent sham operation or filament puncture SAH and were assigned to sham, SAH + vehicle, or SAH + anti-VEGF antibody groups. Vehicle or anti-VEGF antibody was administrated by an intracerebroventricular injection at 30 min post-SAH. After 24 h of SAH modeling, neurological score was recorded to evaluate neurobehavioral functions, brain water content was calculated to assess the level of brain edema, and immunohistochemistry of immunoglobulin (Ig) G was performed to evaluate the permeability of the blood-brain barrier (BBB). Anti-VEGF antibody significantly ameliorated neurological score and brain edema after SAH compared with the SAH + vehicle group. Immunohistochemistry showed that post-SAH IgG extravasation in brain tissue was suppressed by anti-VEGF antibody. This study suggests that VEGF is involved in brain edema formation after SAH, and that anti-VEGF antibody can decrease BBB permeability, suppress brain edema formation, and improve functional outcome after 24 h of SAH.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Fujii M, Yan J, Rolland WB, Soejima Y, Caner B, Zhang JH (2013) Early brain injury, an evolving frontier in subarachnoid hemorrhage research. Transl Stroke Res 4:432–446
Easton AS (2012) Regulation of permeability across the blood–brain barrier. Adv Exp Med Biol 763:1–19
Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676
Roy H, Bhardwaj S, Yla-Herttuala S (2006) Biology of vascular endothelial growth factors. FEBS Lett 580:2879–2887
Jiang S, Xia R, Jiang Y, Wang L, Gao F (2014) Vascular endothelial growth factors enhance the permeability of the mouse blood–brain barrier. PLoS One 9, e86407
Argaw AT, Asp L, Zhang J, Navrazhina K, Pham T, Mariani JN, Mahase S, Dutta DJ, Seto J, Kramer EG, Ferrara N, Sofroniew MV, John GR (2012) Astrocyte-derived VEGF-A drives blood–brain barrier disruption in CNS inflammatory disease. J Clin Invest 122:2454–2468
Suzuki H, Hasegawa Y, Kanamaru K, Zhang JH (2010) Mechanisms of osteopontin-induced stabilization of blood–brain barrier disruption after subarachnoid hemorrhage in rats. Stroke 41:1783–1790
Sugawara T, Ayer R, Jadhav V, Zhang JH (2008) A new grading system evaluating bleeding scale in filament perforation subarachnoid hemorrhage rat model. J Neurosci Methods 167:327–334
Altay O, Suzuki H, Hasegawa Y, Caner B, Krafft PR, Fujii M, Tang J, Zhang JH (2012) Isoflurane attenuates blood–brain barrier disruption in ipsilateral hemisphere after subarachnoid hemorrhage in mice. Stroke 43:2513–2516
Suzuki H, Zhang JH (2012) Neurobehavioral assessments of subarachnoid hemorrhage. In: Chen J, Xu X-M, Xu ZC, Zhang JH (eds) Animal models of acute neurological injuries II, Springer protocols handbooks. Humana Press, New York, pp 435–440
Richmon JD, Fukuda K, Maida N, Sato M, Bergeron M, Sharp FR, Panter SS, Noble LJ (1998) Induction of heme oxygenase-1 after hyperosmotic opening of the blood–brain barrier. Brain Res 780:108–118
Obermeier B, Daneman R, Ransohoff RM (2013) Development, maintenance and disruption of the blood–brain barrier. Nat Med 19:1584–1596
Doczi T (1985) The pathogenetic and prognostic significance of blood–brain barrier damage at the acute stage of aneurysmal subarachnoid haemorrhage. Clinical and experimental studies. Acta Neurochir (Wien) 77:110–132
Yatsushige H, Ostrowski RP, Tsubokawa T, Colohan A, Zhang JH (2007) Role of c-Jun N-terminal kinase in early brain injury after subarachnoid hemorrhage. J Neurosci Res 85:1436–1448
Zhao Y, Li Z, Wang R, Wei J, Li G, Zhao H (2010) Angiopoietin 1 counteracts vascular endothelial growth factor-induced blood–brain barrier permeability and alleviates ischemic injury in the early stages of transient focal cerebral ischemia in rats. Neurol Res 32:748–755
Chi OZ, Hunter C, Liu X, Weiss HR (2007) Effects of anti-VEGF antibody on blood–brain barrier disruption in focal cerebral ischemia. Exp Neurol 204:283–287
Conflict of Interest Statement
We declare that we have no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Liu, L., Fujimoto, M., Kawakita, F., Ichikawa, N., Suzuki, H. (2016). Vascular Endothelial Growth Factor in Brain Edema Formation After Subarachnoid Hemorrhage. In: Applegate, R., Chen, G., Feng, H., Zhang, J. (eds) Brain Edema XVI. Acta Neurochirurgica Supplement, vol 121. Springer, Cham. https://doi.org/10.1007/978-3-319-18497-5_31
Download citation
DOI: https://doi.org/10.1007/978-3-319-18497-5_31
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-18496-8
Online ISBN: 978-3-319-18497-5
eBook Packages: MedicineMedicine (R0)