Impact of anti-angiogenic therapies on microvessel phenotype. Brain tissue was investigated by CD31 immunohistochemistry. A: Representative pictures of brain sections (10-μm thick) stained with anti-CD31 after stereotactic injection of tumor cells (A, upper row, STX) and hematogenous metastases model (A, lower row, ICA) are shown. The experimental groups are indicated. Scale bar represents 50 μm. B, C: The vascular index was calculated as mean±SD for the experimental groups after 16 days survival time (white) or at aprefinal stage (grey). Contralateral (normal) tissue always received a score of 0 (very fine, regular). B: After antiangiogenic treatment, there were more animals with finer blood vessels than in the untreated animals in the STX-model. At 16 days, an irregular architecture was found only in animals which had not been given treatment. After 24 d survival time, animals with a coarse and irregular network of microvessels were found in all groups investigated. C: In the ICA group, treatment had no effect on tumor-induced changes in microvessel morphology (score 0=very fine, regular, score 1=fine, regular, score 2=coarse, regular, score 3=coarse, irregular, ○○ and ○○○ difference versus wt group with p<0.01 and p<0.001, ● and ●● difference between treatment groups as indicated with p<0.05 and p<0.01, respectively. Same abbreviations as in Figure 1).