New vessel formation and expression of angiogenesis-related genes in brain after ischemia

Angiogenesis is an intricately regulated phenomenon. Its mechanisms in the ischemic brain have not been clearly elucidated. We investigated expression of angiogenesis-related genes using a cDNA array method as well as Western blotting and immunohistochemistry, and compared these studies with a temporal profile of angiogenesis in mouse brains after ischemia. The number of vessels significantly increased 3 days after injury, and proliferating endothelial cells increased as early as 1 day. This means angiogenesis occurs immediately after the injury. Ninety-six genes implicated in angiogenesis were investigated with a cDNA array study. We found that 42, 29, and 13 genes were increased at 1 h, and 1 and 21 days, respectively. Most of the well-known angiogenic factors increased as early as 1 h. Vessel stabilizing factors such as thrombospondins also increased. At 1 day, however, thrombospondins decreased to lower than in the control, indicating a shift from vascular protection to angiogenesis. At 21 days, many genes were decreased, but some involved in tissue repair were newly increased. Western blotting and immunohistochemistry revealed findings compatible with the cDNA array study. Many molecules act in an orchestrated fashion in the brain after ischemia, and should be taken into account for therapeutic angiogenesis for stroke. (C) 2003 Elsevier Science B.V All rights reserved.