Peritumoral brain edema in angiomatous supratentorial meningiomas: an investigation of the vascular endothelial growth factor A pathway

Objective: This study aimed to explore the potential mechanism of peritumoral brain edema (PTBE) formation in vestibular schwannoma (VS) by detecting intra-tumoral vascular endothelial growth factor (VEGF) expression.Methods: Between January 2018 and May 2021, 15 patients with PTBE and 25 patients without PTBE were included in the analysis. All patients enrolled in our study underwent surgery in our institution. Expression level of VEGF and microvessel density (MVD) between the two groups were analyzed. Edema index (EI) of each patient with PTBE was calculated.Results: In the PTBE group, the average of EI was 1.53 ± 0.22. VEGF expression levels were significantly enhanced in the PTBE group compared with the non-PTBE group (p < 0.001). The expression level of VEGF in the PTBE group and non-PTBE group was 1.14 ± 0.21 and 0.52 ± 0.09, respectively. Similarly, there were significantly different amounts of MVD in the two groups (p < 0.001). The amount of MVD in the PTBE group and non-PTBE group was 11.33 ± 1.59 and 6.28 ± 1.77, respectively. Correlation analysis showed a highly significant positive correlation between VEGF and MVD (r = 0.883, p < 0.001) and VEGF and EI (r = 0.876, p < 0.001).Conclusion: Our study confirmed the close relationship among VEGF expression, tumor angiogenesis, and formation of PTBE in VS patients. It may be possible to develop new effective therapies to attenuate PTBE in VS for alleviation of symptoms and reduction of postoperative complication.

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Peritumoral brain edema in intracranial meningiomas: the emergence of vascular endothelial growth factor–directed therapy

Neurosurgical FOCUS ◽

10.3171/2013.8.focus13301 ◽

2013 ◽

Vol 35 (6) ◽

pp. E2 ◽

Cited By ~ 52

Author(s):

Jack Hou ◽

Varun R. Kshettry ◽

Warren R. Selman ◽

Nicholas C. Bambakidis

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Brain Edema ◽

Antiangiogenic Therapy ◽

Mass Effect ◽

Vascular Endothelial ◽

Close Relationship ◽

Peritumoral Brain Edema ◽

Endothelial Growth Factor

Meningioma is the second most common type of adult intracranial neoplasm. A substantial subset of patients present with peritumoral brain edema (PTBE), which can cause significant morbidity via mass effect, complicate surgical management, and impact the safety of stereotactic radiosurgery. Recent studies suggest a close relationship between vascular endothelial growth factor-A (VEGF-A) expression and PTBE development in meningiomas. The authors performed a systematic review of the literature on the pathogenesis of PTBE in meningiomas, the effectiveness of steroid therapy, the role played by VEGF-A, and the current clinical evidence for antiangiogenic therapy to treat peritumoral brain edema. Mounting evidence suggests VEGF-A is secreted directly by meningioma cells to induce angiogenesis and edemagenesis of tumoral as well as peritumoral brain tissue. The VEGF-A cascade results in recruitment of cerebral-pial vessels and disruption of the tumor-brain barrier, which appear to be requisite for VEGF-A to have an edemagenic effect. Results of preliminary clinical studies suggest VEGF-directed therapy has modest activity against recurrent and progressive meningioma growth but can alleviate PTBE in some patients. A comprehensive understanding of the VEGF-A pathway and its modulators may hold the key to an effective therapeutic approach to treating PTBE associated with meningiomas. Further clinical trials with larger patient cohorts and longer follow-up periods are warranted to confirm the efficacy of VEGF-directed therapy.

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The relationship between peritumoral brain edema and the expression of vascular endothelial growth factor and its receptors in intracranial meningiomas

Journal of Neuro-Oncology ◽

10.1007/s11060-004-9164-4 ◽

2004 ◽

Vol 70 (3) ◽

pp. 349-357 ◽

Cited By ~ 53

Author(s):

Shinji Otsuka ◽

Takashi Tamiya ◽

Yasuhiro Ono ◽

Hiroyuki Michiue ◽

Kazuhiko Kurozumi ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Brain Edema ◽

Vascular Endothelial ◽

Intracranial Meningiomas ◽

Peritumoral Brain Edema ◽

Endothelial Growth Factor ◽

The Relationship

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Vascular Endothelial Growth Factor in Brain Edema Formation After Subarachnoid Hemorrhage

Acta Neurochirurgica Supplement - Brain Edema XVI ◽

10.1007/978-3-319-18497-5_31 ◽

2016 ◽

pp. 173-177 ◽

Cited By ~ 9

Author(s):

Lei Liu ◽

Masashi Fujimoto ◽

Fumihiro Kawakita ◽

Naoki Ichikawa ◽

Hidenori Suzuki

Keyword(s):

Vascular Endothelial Growth Factor ◽

Subarachnoid Hemorrhage ◽

Growth Factor ◽

Brain Edema ◽

Vascular Endothelial ◽

Edema Formation ◽

Endothelial Growth Factor ◽

Brain Edema Formation

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The Endothelin ETB Receptor Antagonist BQ788 Protects against Brain Edema after Fluid Percussion Injury by Decreasing Vascular Endothelial Growth Factor-A Expression in Mice

YAKUGAKU ZASSHI ◽

10.1248/yakushi.17-00134 ◽

2017 ◽

Vol 137 (10) ◽

pp. 1241-1246

Author(s):

Shotaro Michinaga

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Receptor Antagonist ◽

Brain Edema ◽

Vascular Endothelial ◽

Fluid Percussion ◽

Fluid Percussion Injury ◽

Endothelial Growth Factor

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Expression of MMP-9 and VEGF in Meningiomas and Their Correlation with Peritumoral Brain Edema

BioMed Research International ◽

10.1155/2015/646853 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 21

Author(s):

Joanna Reszec ◽

Adam Hermanowicz ◽

Robert Rutkowski ◽

Grzegorz Turek ◽

Zenon Mariak ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Brain Edema ◽

Lower Grade ◽

Vascular Endothelial ◽

High Grade ◽

Intracranial Tumors ◽

Limited Data ◽

Peritumoral Brain Edema ◽

Endothelial Growth Factor

Meningiomas constitute up to 13% of all intracranial tumors. The predictive factors for meningioma have not been unambiguously defined; however some limited data suggest that the expression of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) may be associated with the presence of peritumoral brain edema (PTBE) and worse clinical outcome. The aim of this study was to analyze the expressions of MMP-9 and VEGF in a group of meningiomas of various grades and to study associations between these two markers and PTBE. The study included patients with supratentorial meningiomas. The patients were divided into low- (G1) and high-grade meningiomas (G2 and G3). PTBE was assessed on MRI. The expressions of VEGF and MMP-9 were determined immunohistochemically. The expression of MMP-9 was observed significantly more often in G3 meningiomas than in lower grade tumors. The presence of stage II or III PTBE was associated with a significant increase in MMP-9 expression. The expression of VEGF did not differ across the PTBE stages. Our findings point to a significant role of MMP-9 and VEGF in the pathogenesis of peritumoral brain edema in low- and high-grade meningiomas.

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Intraventricular Infusion of Vascular Endothelial Growth Factor Promotes Cerebral Angiogenesis with Minimal Brain Edema

Neurosurgery ◽

10.1097/00006123-200203000-00030 ◽

2002 ◽

Vol 50 (3) ◽

pp. 589-598 ◽

Cited By ~ 7

Author(s):

Mark R. Harrigan ◽

Steven R. Ennis ◽

Tetsuya Masada ◽

Richard F. Keep

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Brain Edema ◽

Capillary Permeability ◽

Vascular Endothelial ◽

Brain Water Content ◽

Endothelial Growth Factor ◽

Intraventricular Infusion ◽

Evans Blue Extravasation ◽

Brain Water

Abstract OBJECTIVE: Therapeutic cerebral angiogenesis, i.e., using angiogenic factors to enhance collateral vessel formation within the central nervous system, is a potential method for cerebral revascularization. Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen that also increases capillary permeability, particularly in ischemic tissue. The purpose of this study was to assess the angiogenic and capillary permeability effects of chronic intraventricular infusion of exogenous VEGF in nonischemic brain tissue, because many patients with impaired cerebrovascular reserve do not exhibit chronic cerebral ischemia. METHODS: Recombinant human VEGF165 was infused into the right lateral ventricle of rats at a rate of 1 μl/h for 7 days, at concentrations of 1 to 25 μg/ml, with osmotic minipumps. Control animals received vehicle only. Vessels were identified in laminin immunohistochemical analyses. Capillary permeability and brain edema were assessed with Evans blue extravasation, [3H]inulin permeability, and brain water content measurements. RESULTS: Vessel density was dose-dependently increased by VEGF165 infusions, with significant increases occurring in animals treated with 5 or 25 μg/ml, compared with control animals (P < 0.01). Significant enlargement of the lateral ventricles was observed for the highest-dose group but not for animals treated with other doses. Capillary permeability was assessed in animals treated with a dose of 5 μg/ml. An increase in capillary permeability in the diencephalon was identified with Evans blue extravasation and [3H]inulin permeability assessments; however, the brain water content was not significantly increased. CONCLUSION: Chronic intraventricular infusions of VEGF165 increased vascular density in a dose-dependent manner. There seems to be a therapeutic window, because infusion of VEGF165 at a concentration of 5 μg/ml resulted in a significant increase in vessel density with minimal associated brain edema and no ventriculomegaly.

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