title: Rabbit Model of Human Gliomas: Implications for Intra-Arterial Drug Delivery.
abstract: The prognosis for malignant brain tumors remains poor despite a combination of surgery, radiotherapy, and chemotherapy. This is partly due to the blood-brain barrier, a major obstacle that prevents therapeutic agents from effectively reaching the tumor. We have recently developed a method for precise and predictable opening of the blood-brain barrier via the intra-arterial administration of mannitol, a hyperosmolar agent, in a rabbit model, whose vascular anatomy facilitates the use of standard interventional neuroradiology techniques and devices. To date, however, no protocols are available that enable human glioma modeling in rabbits. In this article, we report on the xenotransplantation of a human glioblastoma (GBM-1) in adult New Zealand rabbits. We induced multi-drug immunosuppression (Mycophenolate Mofetil, Dexamethasone, Tacrolimus) and stereotactically implanted GBM-1 tumor cells into rabbit brains. The rabbits were followed for 42 days, monitored by MRI and body weight measurements, and underwent postmortem histopathological analysis. On MRI, brain tumors were identified on T2-weighted scans. On histopathology, tumors were detected with hematoxylin/eosin and their human origin was confirmed with immunohistochemistry against human-specific antigens. Our method for human glioma modeling in rabbits provides the foundation to test novel treatment strategies, including intra-arterial therapeutic agent delivery.
authors.affiliation: Russell H. Morgan Department. of Radiology and Radiological Science, Division of MR Research, Cellular Imaging Section, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.|Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.|Department of Pathology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Huamin
authors.initials: H
authors.lastname: Qin
authors.affiliation: Russell H. Morgan Department. of Radiology and Radiological Science, Division of MR Research, Cellular Imaging Section, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.|Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.|NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Janowski
authors.affiliation: Division of Interventional Neuroradiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Monica S
authors.initials: MS
authors.lastname: Pearl
authors.affiliation: Department of Neurology and Neurosurgery, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Malysz-Cymborska
authors.affiliation: Russell H. Morgan Department. of Radiology and Radiological Science, Division of MR Research, Cellular Imaging Section, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.|Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Shen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Eberhart
authors.affiliation: Russell H. Morgan Department. of Radiology and Radiological Science, Division of MR Research, Cellular Imaging Section, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.|Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.|Department of Neurology and Neurosurgery, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland.
authors.forename: Piotr
authors.identifier: http://orcid.org/0000-0002-3733-3322
authors.initials: P
authors.lastname: Walczak
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001932:Brain Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005910:Glioma / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy*; D064593:Heterografts; D006801:Humans; D007261:Infusions, Intra-Arterial; D008279:Magnetic Resonance Imaging; D008353:Mannitol / Q000008:administration & dosage*; D009994:Osmolar Concentration; D011817:Rabbits
chemical_list: D008353:Mannitol