Article
Expression of iNOS, VEGF-A and AQP4 in human peritumoral brain edema tissue and their correlation with brain edema
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Authors
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Svorad Trnovec
- Universitätsmedizin Rostock, Abteilung für Neurochirurgie, Rostock, Deutschland
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Benedikt Trnovec
- Klinikum Augsburg, Klinik für Neurochirurgie, Augsburg, Deutschland
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Kay Mursch
- Zentralklinik Bad Berka, Klinik für Neurochirurgie, Bad Berka, Deutschland
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Steffen Sola
- Universitätsmedizin Rostock, Abteilung für Neurochirurgie, Rostock, Deutschland
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Heidecke Volkmar
- Klinikum Augsburg, Klinik für Neurochirurgie, Augsburg, Deutschland
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Jürgen Piek
- Universitätsmedizin Rostock, Abteilung für Neurochirurgie, Rostock, Deutschland
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Pavel Babál
- Institute of Pathology, Medical Faculty Commenius University, Bratislava, Slovakia
| Published: | June 9, 2017 |
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Outline
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Objective: NO is synthesized in living organisms by the enzyme NO-synthase (NOS I-III) and plays an important role in physiological as well as in pathological processes within the brain. One of these processes is the cerebral edema, which may become a life-threatening problem. Cerebral edema is defined as a high content of water in the brain tissue. The peritumoral brain edema is a typical example of vasogenic edema, when the blood-brain barrier function fails due to angioneogenesis. Histological studies have demonstrated an increased expression of various factors in the tumor cells that stimulate angioneogenesis, which is designed to compensate local hypoxia. Such factors are NOS and vascular endothelial growth factor (VEGF). An elevated expression of Aquaporin 4 (AQP4) has also been demonstrated, especially in cells of glial tumors. NO is a cofactor in the regulation of VEGF expression and is also involved in the regulation of AQP4 function. However, the expression of these factors in human peritumoral edematous tissue and their correlation with peritumoral edema volume has not been investigated so far.
Methods: In this study, we assessed the expression of iNOS, AQP4 and VEGF-A in peritumoral edematous brain tissue in 50 patients (31 suffering from glioblastoma, 2 anaplastic astrocytoma, 1 malignant meningeoma, 2 lymphomas and 14 metastases) in whom the tumor was excised by supra-maximal resection. The study had been approved by our local ethic committee. 3 patients with glioblastoma underwent frontal lobe resection. From these patients it was possible to obtain non edematous brain tissue, which was used as control. The expression of iNOS, AQP4 and VEGF-A was investigated by immunohistochemical staining. Volume of tumor and peritumoral edema was measured with BrainLab software, the edema index (EI) was calculated as a ratio: edema volume +tumor volume / tumor volume. Furthermore, we correlated the expression of iNOS, AQP4 and VEGF-A with the peritumoral edema volume expressed by EI.
Results: We detected increased expression of iNOS, AQP4 and VEGF-A in the examined tissue when compared to the control brain tissue. We also observed a significant correlation between the expression of AQP4 and the EI. There was no significant correlation between increased expression of iNOS and VEGF-A in peritumoral edematous tissue and the EI.
Conclusion: Based on our results, we can regard the expression of AQP4 as a quantitative marker of EI, while the expression of iNOS and VEGF only as qualitative attributes of EI. Elucidation of peritumoral edema constituting pathways and factors affecting the extent of peritumoral edema is the key to causal therapy of edema and thus, further studies on interaction pathways between tumor and brain tissue should proceed
