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Molecular Neurobiology

, Volume 55, Issue 6, pp 4918–4926 | Cite as

Loss of Pericytes in Radiation Necrosis after Glioblastoma Treatments

  • Soon-Tae Lee
  • Youngbeom Seo
  • Ji-Yeon Bae
  • Kon Chu
  • Jin Wook Kim
  • Seung Hong Choi
  • Tae Min Kim
  • Il Han Kim
  • Sung-Hye Park
  • Chul-Kee Park
Original Paper

Abstract

Radiation necrosis (RN) in brain tumor patients is often symptomatic, persistent without immediate resolution, and confused with tumor recurrence. Cerebral vascular pericytes are essential for endothelial function, vascular integrity, and angiogenesis. In this study, we showed that the loss of pericytes is involved in the pathogenesis of RN. From a brain tumor tissue repository, we identified three patients since 2011 with pathologically confirmed RN after the standard treatment for glioblastoma (GBM). The RN and their preradiation GBM tissues were serially processed for Western blotting using cell-type-specific antibodies against endothelial (CD31, active RhoA), pericyte [platelet-derived growth factor receptor-beta (PDGFR-β)], alpha-smooth muscle actin (α-SMA), astrocyte (GFAP), myelin sheath protein (MBP), and microglial markers (Iba1). Normal brain tissues from a brain bank were used as normal controls. The expressions of PDGFR-β and α-SMA were remarkably reduced in the RN, compared to those of GBM. However, the levels of CD31 or RhoA were not different between the two groups, which suggest that there was no change in the number of endothelial cells or their cytoskeletal assembly. The RN tissues showed a decreased ratio of pericyte/endothelial markers and an increased level of Iba1 compared to the GBM and even to the normal brain. The levels of GFAP and MBP were not changed in the RN. In the histopathology, the RN tissues showed a loss of markers (PDGFR-β), whereas the GBM tissues had abundant expression of the markers. The loss of pericytes and vascular smooth muscle cells, and the unsupported endothelial cells might be the cause of the leaky blood-brain barrier and tissue necrosis.

Keywords

Radiation necrosis Glioblastoma Pericytes Endothelial cells Microglia 

Notes

Acknowledgements

This research was supported by the National Research Foundation of Korea (NRF) grants funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (2016M3C7A1914002 by the Brain Research Program, and 2016R1C1B2011815). S.-T.L. was supported by the SNUH Research Fund (0420150850). We are thankful for the artwork done by Mijin Jung.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of NeurologySeoul National University HospitalSeoulKorea
  2. 2.Department of NeurosurgeryYeungnam University College of MedicineDaeguKorea
  3. 3.Department of NeurosurgerySeoul National University Hosptial, Seoul National University College of MedicineSeoulKorea
  4. 4.Department of RadiologySeoul National University Hospital, Seoul National University College of MedicineSeoulKorea
  5. 5.Department of Internal MedicineSeoul National University HospitalSeoulKorea
  6. 6.Department of Radiation OncologySeoul National University Hospital, Seoul National University College of MedicineSeoulKorea
  7. 7.Department of PathologySeoul National University Hospital, Seoul National University College of MedicineSeoulKorea

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