E-ISSN 2146-8362
 

Original Research 


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.

Cited by (4)

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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REFERENCES
1. Babcock MA, Kostova FV, Guha A, Packer RJ, Pollack IF, Maria BL. Tumors of the central nervous system: Clinical aspects, molecular mechanisms, unanswered questions, and future research directions. J Child Neurol 2008;23:1103-21. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   
2. Rubin LL, Barbu K, Bard F, Cannon C, Hall DE, Horner H, et al. Differentiation of brain endothelial cells in cell culture. Ann N Y Acad Sci 1991;633:420-5. [DOI via Crossref]    [Pubmed]   
3. Cyrine S, Sonia Z, Mounir T, Badderedine S, Kalthoum T, Hedi K, et al. Pilocytic astrocytoma: A retrospective study of 32 cases. Clin Neurol Neurosurg 2013;115:1220-5. [DOI via Crossref]    [Pubmed]   
4. Akay KM, Izci Y, Baysefer A, Atabey C, Kismet E, Timurkaynak E. Surgical outcomes of cerebellar tumors in children. Pediatr Neurosurg 2004;40:220-5. [DOI via Crossref]    [Pubmed]   
5. Nduom EK, Yang C, Merrill MJ, Zhuang Z, Lonser RR. Characterization of the blood-brain barrier of metastatic and primary malignant neoplasms. J Neurosurg 2013;119:427-33. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   
6. Gundersen GA, Vindedal GF, Skare O, Nagelhus EA. Evidence that pericytes regulate aquaporin-4 polarization in mouse cortical astrocytes. Brain Struct Funct 2014;219:2181-6. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   
7. Roales-Buján R, Páez P, Guerra M, RodrĂ­guez S, VĂ­o K, Ho-Plagaro A, et al. Astrocytes acquire morphological and functional characteristics of ependymal cells following disruption of ependyma in hydrocephalus. Acta Neuropathol 2012;124:531-46. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   
8. Lee YY, Van Tassel P, Bruner JM, Moser RP, Share JC. Juvenile pilocytic astrocytomas: CT and MR characteristics. AJR Am J Roentgenol 1989;152:1263-70. [DOI via Crossref]    [Pubmed]   
9. Coakley KJ, Huston J 3rd, Scheithauer BW, Forbes G, Kelly PJ. Pilocytic astrocytomas: Well-demarcated magnetic resonance appearance despite frequent infiltration histologically. Mayo Clin Proc 1995;70:747-51. [DOI via Crossref]    [Pubmed]   
10. Palma L, Guidetti B. Cystic pilocytic astrocytomas of the cerebral hemispheres. Surgical experience with 51 cases and long-term results. J Neurosurg 1985;62:811-5. [DOI via Crossref]    [Pubmed]   
11. Fruehwald-Pallamar J, Puchner SB, Rossi A, Garre ML, Cama A, Koelblinger C, et al. Magnetic resonance imaging spectrum of medulloblastoma. Neuroradiology 2011;53:387-96. [DOI via Crossref]    [Pubmed]   
12. Yeom KW, Mobley BC, Lober RM, Andre JB, Partap S, Vogel H, et al. Distinctive MRI features of pediatric medulloblastoma subtypes. AJR Am J Roentgenol 2013;200:895-903. [DOI via Crossref]    [Pubmed]   
13. Moschovi M, Koultouki E, Stefanaki K, Sfakianos G, Tourkantoni N, Prodromou N, et al. Prognostic significance of angiogenesis in relation to Ki-67, p-53, p-27, and bcl-2 expression in embryonal tumors. Pediatr Neurosurg 2011;47:241-7. [DOI via Crossref]    [Pubmed]   
14. MacDonald TJ, Taga T, Shimada H, Tabrizi P, Zlokovic BV, Cheresh DA, et al. Preferential susceptibility of brain tumors to the antiangiogenic effects of an alpha(v) integrin antagonist. Neurosurgery 2001;48:151-7. [Pubmed]   
15. Claes A, Idema AJ, Wesseling P. Diffuse glioma growth: A guerilla war. Acta Neuropathol 2007;114:443-58. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   
16. Karajannis MA, Legault G, Fisher MJ, Milla SS, Cohen KJ, Wisoff JH, et al. Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytomas. Neuro Oncol 2014;16:1408-16. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   
17. Gururangan S, Chi SN, Young Poussaint T, Onar-Thomas A, Gilbertson RJ, Vajapeyam S, et al. Lack of efficacy of bevacizumab plus irinotecan in children with recurrent malignant glioma and diffuse brainstem glioma: A pediatric brain tumor consortium study. J Clin Oncol 2010;28:3069-75. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   
18. Terashima K, Chow K, Jones J, Ahern C, Jo E, Ellezam B, et al. Longterm outcome of centrally located low-grade glioma in children. Cancer 2013;119:2630-8. [DOI via Crossref]    [Pubmed]   
19. Doolittle ND, Muldoon LL, Culp AY, Neuwelt EA. Delivery of chemotherapeutics across the blood-brain barrier: Challenges and advances. Adv Pharmacol 2014;71:203-43. [DOI via Crossref]    [Pubmed]   
20. Gilbert MR, Wang M, Aldape KD, Stupp R, Hegi ME, Jaeckle KA, et al. Dose-dense temozolomide for newly diagnosed glioblastoma: A randomized phase III clinical trial. J Clin Oncol 2013;31:4085-91. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   
21. Shaw EG, Wang M, Coons SW, Brachman DG, Buckner JC, Stelzer KJ, et al. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: Initial results of RTOG 9802. J Clini Oncol 2012;30:3065-70. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   

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How to Cite this Article
Pubmed Style

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


Web Style

Christopher S Hong, Winson Ho, Martin G Piazza, Abhik Ray-Chaudhury, Zhengping Zhuang, John D Heiss. Characterization of the Blood Brain Barrier in Pediatric Central Nervous System Neoplasms. http://www.ejmjih.com/?mno=230722 [Access: December 12, 2018]. doi:10.5455/jihp.20160623053540


AMA (American Medical Association) Style

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



Vancouver/ICMJE Style

Christopher S Hong, Winson Ho, Martin G Piazza, Abhik Ray-Chaudhury, Zhengping Zhuang, John D Heiss. Characterization of the Blood Brain Barrier in Pediatric Central Nervous System Neoplasms. J Interdiscip Histopathol. (2016), [cited December 12, 2018]; 4(2): 29-33. doi:10.5455/jihp.20160623053540



Harvard Style

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



Turabian Style

Christopher S Hong, Winson Ho, Martin G Piazza, Abhik Ray-Chaudhury, Zhengping Zhuang, 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

Christopher S Hong, Winson Ho, Martin G Piazza, Abhik Ray-Chaudhury, Zhengping Zhuang, 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

Christopher S Hong, Winson Ho, Martin G Piazza, Abhik Ray-Chaudhury, Zhengping Zhuang, 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

Christopher S Hong, Winson Ho, Martin G Piazza, Abhik Ray-Chaudhury, Zhengping Zhuang, 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





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