title: Characterization of the blood brain barrier in pediatric central nervous system neoplasms.
abstract: OBJECTIVE
  The normal blood-brain barrier (BBB) is composed of tight junctions between endothelial cells and surrounding astrocyte foot processes. Breakdown of the physiological astrocyte-endothelial cell relationship occurs in adult metastatic and primary brain tumors. However, the astrocyte-endothelial cell relationship has not been studied in pediatric tumors.
  
  
  METHODS
  Utilizing specimens from cases of pilocytic astrocytoma (n = 5), medulloblastoma (n = 5), and low-grade diffuse astrocytoma (n = 1), immunofluorescence were performed using primary antibodies against CD31, glial fibrillary acidic protein (GFAP), and aquaporin 4 (AQ4). Clinical, magnetic resonance imaging, operative, and histopathological findings were analyzed.
  
  
  RESULTS
  Strongly-enhancing areas of medulloblastoma exhibited complete BBB breakdown with sparse GFAP and AQ4 staining around CD31-positive vessels. Moderately enhancing regions of pilocytic astrocytomas exhibited regions of intact BBB and vasculature surrounded by dense GFAP staining but reduced and disorganized AQ4 staining, suggesting tumor cells could not fulfill physiological BBB support. Non-enhancing low-grade diffuse astrocytoma demonstrated intact BBB with intense peri-microvasculature GFAP and AQ4 staining. AQ4 stained so strongly that AQ4 visualization alone delineated CD31-positive vessels.
  
  
  CONCLUSIONS
  Taken together, BBB breakdown in pediatric tumors corresponds to a loss of normal endothelial cell-astrocyte foot process relationships. Further development of pharmaceutical agents capitalizing on this disrupted BBB is warranted in medulloblastoma and pilocytic astrocytoma. However, BBB integrity remains a challenge in treating low-grade diffuse astrocytoma before progression toward secondary glioblastoma.
authors.affiliation: Department of Surgical Neurology Branch, National Institutes of Health, Bethesda, MD 20892, USA ; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, 06510, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Hong
authors.affiliation: Department of Surgical Neurology Branch, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Winson
authors.initials: W
authors.lastname: Ho
authors.affiliation: Department of Surgical Neurology Branch, National Institutes of Health, Bethesda, MD 20892, USA ; Department of Neurosurgery, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Piazza
authors.affiliation: Department of Surgical Neurology Branch, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Abhik
authors.initials: A
authors.lastname: Ray-Chaudhury
authors.affiliation: Department of Surgical Neurology Branch, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: Department of Surgical Neurology Branch, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Heiss
keywords: Blood–brain barrier; glioma; medulloblastoma; pediatric brain tumor; pilocytic astrocytoma