A Pial Window Model for the Intracranial Study of Human Glioma Microvascular Function

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Abstract
A NEW MODEL for human brain tumor uses the intracranial placement of tumor xenografts under transparent glass cranial windows in nude rats, which require no immunosuppression for tumor engraftment. Adult male nude rats underwent implantation of human anaplastic astrocytomas (D-54 MG in 10 rats, D-317 MG in 11 rats). The tumors were placed on the pial surface of the left cerebral hemisphere under a glass cranial window overlying the cranium. Six control animals underwent cranial window placement alone. Tumor volumes were estimated from direct measurements of tumor dimensions, revealing a mean doubling time of 1.58 days for the D-54 MG tumors and 2.62 days for the D-317 MG tumors. When tumor volume estimates reached 35 mm3, photomicrographs revealed tumor vasculature in each tumor cell line that was distinct from both the other xenograft and the normal brain parenchyma. Qualitative differences in vascular appearance were supported by length/density coefficient calculations in each study group, with D-317 MG demonstrating the highest vascular density. Vessel caliber tended to be smaller in D-54 MG tumors than in D-317 MG tumors. Laser-Doppler measurements of local blood flow in tumors and normal parenchyma revealed significantly lower blood flow in both tumor cell lines than in control brain. Evaluation of leukocyte/endothelial cell interactions indicated more leukocyte rolling in D-54 MG tumors than in D-317 MG tumors; no evidence of this cell interaction was found in normal pial vasculature. This model allows direct serial inspection of human brain tumor growth and vascular function in an experimental animal and could be used to study tumor vascular and inflammatory responses to a variety of therapeutic manipulations.

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