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  • Variations in Blood-Brain Barrier Disruption in Metastatic and Primary Brain Neoplasms

    Final Number:

    Shervin Rahimpour; Jason Michael Frerich; Marsha J. Merrill PhD; John D. Heiss MD; Zhengping Zhuang MD, PhD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2013 Annual Meeting

    Introduction: The effects of metastatic and primary brain neoplasms on the blood-brain barrier are poorly understood. To better understand this interaction, the morphology of the astrocytic component and blood brain barrier structural and functional proteins in the peritumoral region can be analyzed.

    Methods: 9 patients that underwent resection of metastatic or primary brain neoplasms (5 metastases, 1 low grade astrocytoma, 2 anaplastic astrocytomas, 1 glioblastoma) were included in the study. Magnetic resonance (MR)-imaging, histopathologic and immunohistochemical (glial fibrillary acidic protein [GFAP], CD31, tight junction protein zona-occludin 1 [ZO-1], and P-glycoprotein [C219]) findings were analyzed.

    Results: Metastases including melanoma and colorectal cancer, demonstrated lack of perivascular GFAP, P-glycoprotein, and discontinuous ZO-1 on CD31 positive intratumoral vessels. Low grade astrocytoma maintained integrity of the neurovascular architecture while anaplastic astrocytoma and glioblastoma demonstrated reactive astrocytic architecture and discontinuous immunofluorescent staining for ZO-1 and the presence of P-glycoprotein. Neurovascular compromise in gliomas as seen by immunofluorescence was, however, less than that of metastatic lesions.

    Conclusions: Regions of MR-imaging enhancement in metastatic malignancies correspond to areas of structural (including the astrocytic component and tight-junction proteins) and functional (P-glycoprotein) disruption. Low grade gliomas of the brain maintain both structural and functional integrity while high grade gliomas do not. Structural and functional compromise of the blood-brain barrier is greatest in metastatic lesions.

    Patient Care: The physiology and structural alterations of the blood-brain barrier are essential in understanding tumor metastasis dynamics as well as key information regarding the delivery of therapeutic agents.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the integral components of the blood-brain barrier 2) Discuss the differences in blood-brain barrier breakdown between metastatic and primary neoplasms.

    References: 1. Wilhelm I, et al. Int J Mol Sci. 2013 Jan 11;14(1):1383-411 2. Wolburg H, et al. Mol Aspects Med. 2012 Oct-Dec;33(5-6):579-89

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