Extracellular matrix (ECM) molecules play important roles in the pathobiology of the major human central nervous system (CNS) inflammatory/demyelinating disease multiple sclerosis (MS). This mini-review highlights some recent work on CNS endothelial cell interactions with vascular basement membrane ECM as part of the cellular immune response, and roles for white matter ECM molecules in demyelination and remyelination in MS lesions. Recent basic and clinical investigations of MS emphasize axonal injury, not only in chronic MS plaques, but also in acute lesions; progressive axonal degeneration in normal-appearing white matter also may contribute to brain and spinal cord atrophy in MS patients. Remodeling of the interstitial white matter ECM molecules that affect axon regeneration, however, is incompletely characterized. Our ongoing immunohistochemical studies demonstrate enhanced ECM versican, a neurite and axon growth-inhibiting white matter ECM proteoglycan, and dermatan sulfate proteoglycans at the edges of inflammatory MS lesions. This suggests that enhanced proteoglycan deposition in the ECM and axonal growth inhibition may occur early and are involved in expansion of active lesions. Decreased ECM proteoglycans and their phagocytosis by macrophages along with myelin in plaque centers imply that there is injury to the ECM itself. These results indicate that white matter ECM proteoglycan alterations are integral to MS pathology at all disease stages and that they contribute to a CNS ECM that is inhospitable to axon regrowth/regeneration.

To develop a reproducible in vivo model for the growth of human meningiomas, meningiomas from 16 patients were implanted into the subrenal capsule of the nude mouse. In eight experiments solid tumor implants taken directly from surgical specimens were used, in four experiments the implants were made from early-passage monolayer cell cultures, and in four experiments both techniques were used. Successful tumor growth was observed in 10 (83%) of the 12 solid tumor implants and in six (75%) of the eight implants from cell cultures. The size and neovascularization of these tumors were serially determined over a 3-month period. Tumor doubling occurred in 1 to 3 weeks in all of the solid tumor implant group. In the group of six tumors successfully implanted from cell cultures, three doubled in 1 to 3 weeks and three grew more rapidly, reaching 10 to 20 times their original volume. Neovascularity occurred in the tumors within 3 weeks of implantation. Each of the solid tumor implants had a histological pattern similar to that of the corresponding original specimen. Only three of those implanted from cell cultures were similar to the original tumor; the other three displayed features characteristic of malignant meningioma. These studies suggest that implantation of human meningiomas in the subrenal capsule of the nude mouse is a feasible model that may be useful for evaluating hormonal or genetic modulation of tumor growth and for testing potential treatment regimens.