EXPRESSION OF BASEMENT-MEMBRANE AND ENDOTHELIAL-CELL ADHESION MOLECULES IN VASCULAR MALFORMATIONS OF THE BRAIN - PRELIMINARY-OBSERVATIONS AND WORKING HYPOTHESIS

Little is known about the pathogenesis and subsequent cellular biologi c behaviour of human cerebral vascular malformations. Innovative thera peutic strategies will depend on more fundamental understanding of str uctural and functional lesion biology. We have freeze-processed four s pecimens of arteriovenous malformation (AVM), two cavernous malformati ons (CM), and resected cortex from one case of Sturge-Weber disease (S WD) for immunohistochemical studies. Probes of vascular maturity and c ellular adhesion were examined, including Factor 8 related antigen (F8 RAG), laminin, fibronectin, and adhesion molecules VCAM, ELAM and ICAM -1 (CD 54). Sections of the same lesions were permanently fixed and st ained using Haematoxylin and Eosin, and MOVAT Pentachrome stain for id entification of vascular wall structures. A double antibody staining b attery was utilized with ultraviolet fluorescent microscopy, and was a nalysed by an observer blinded to the antibody and lesion type. All ma lformations showed strong expression on their luminal endothelial surf ace for F8RAG. There was no expression of ELAM in any lesion. Two AVMs expressed VCAM on the endothelial surface of some vessels. ICAM-1 was expressed faintly within two AVMs. The CMs expressed fibronectin with in the endothelium and subendothelial matrix and both lesions were dev oid oi laminin expression. The AVMs and the SWD vessels stained for la minin, while none of the AVMs expressed fibronectin. These preliminary observations are consistent with the hypothesis that AVMs and SWD rep resent more mature vessels, consistent with possible lesion genesis du ring early phases of embryonic vascular development (dysvasculogenesis ). In contrast CMs represent immature vessels devoid of laminin and ot her features of mature vessels, consistent with ongoing dysangiogenesi s within a fibronectin rich matrix. Further studies should be aimed at better elucidation of these biologic probes, and correlation with spe cific lesion behaviour.