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Characterization of the Blood Brain Barrier in Pediatric Central Nervous System Neoplasms

Christopher S Hong, Winson Ho, Martin G Piazza, Abhik Ray-Chaudhury, Zhengping Zhuang, John D Heiss.

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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. Materials and 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. Conclusion: 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.

Key words: blood brain barrier, pediatric brain tumor, glioma, pilocytic astrocytoma, medulloblastoma


 
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This Article Cited By the following articles

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2017; 64(CN_suppl_1): 165.

1
 

How to Cite this Article
Pubmed Style

Hong CS, Ho W, Piazza MG, Ray-Chaudhury A, Zhuang Z, Heiss JD. Characterization of the Blood Brain Barrier in Pediatric Central Nervous System Neoplasms. J Interdiscipl Histopathol. 2016; 4(2): 29-33. doi:10.5455/jihp.20160623053540


Web Style

Hong CS, Ho W, Piazza MG, Ray-Chaudhury A, Zhuang Z, Heiss JD. Characterization of the Blood Brain Barrier in Pediatric Central Nervous System Neoplasms. http://www.ejmjih.com/?mno=230722 [Access: February 23, 2018]. doi:10.5455/jihp.20160623053540


AMA (American Medical Association) Style

Hong CS, Ho W, Piazza MG, Ray-Chaudhury A, Zhuang Z, Heiss JD. Characterization of the Blood Brain Barrier in Pediatric Central Nervous System Neoplasms. J Interdiscipl Histopathol. 2016; 4(2): 29-33. doi:10.5455/jihp.20160623053540



Vancouver/ICMJE Style

Hong CS, Ho W, Piazza MG, Ray-Chaudhury A, Zhuang Z, Heiss JD. Characterization of the Blood Brain Barrier in Pediatric Central Nervous System Neoplasms. J Interdiscipl Histopathol. (2016), [cited February 23, 2018]; 4(2): 29-33. doi:10.5455/jihp.20160623053540



Harvard Style

Hong, C. S., Ho, W., Piazza, M. G., Ray-Chaudhury, A., Zhuang, Z. & Heiss, J. D. (2016) Characterization of the Blood Brain Barrier in Pediatric Central Nervous System Neoplasms. J Interdiscipl Histopathol, 4 (2), 29-33. doi:10.5455/jihp.20160623053540



Turabian Style

Hong, Christopher S, Winson Ho, Martin G Piazza, Abhik Ray-Chaudhury, Zhengping Zhuang, and John D Heiss. 2016. Characterization of the Blood Brain Barrier in Pediatric Central Nervous System Neoplasms. Journal of Interdisciplinary Histopathology, 4 (2), 29-33. doi:10.5455/jihp.20160623053540



Chicago Style

Hong, Christopher S, Winson Ho, Martin G Piazza, Abhik Ray-Chaudhury, Zhengping Zhuang, and John D Heiss. "Characterization of the Blood Brain Barrier in Pediatric Central Nervous System Neoplasms." Journal of Interdisciplinary Histopathology 4 (2016), 29-33. doi:10.5455/jihp.20160623053540



MLA (The Modern Language Association) Style

Hong, Christopher S, Winson Ho, Martin G Piazza, Abhik Ray-Chaudhury, Zhengping Zhuang, and John D Heiss. "Characterization of the Blood Brain Barrier in Pediatric Central Nervous System Neoplasms." Journal of Interdisciplinary Histopathology 4.2 (2016), 29-33. Print. doi:10.5455/jihp.20160623053540



APA (American Psychological Association) Style

Hong, C. S., Ho, W., Piazza, M. G., Ray-Chaudhury, A., Zhuang, Z. & Heiss, J. D. (2016) Characterization of the Blood Brain Barrier in Pediatric Central Nervous System Neoplasms. Journal of Interdisciplinary Histopathology, 4 (2), 29-33. doi:10.5455/jihp.20160623053540





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