Transforming growth factor α induces angiogenesis and neurogenesis following stroke

Abstract

The cytokine transforming growth factor α (TGFα) has proangiogenic and proneurogenic effects and can potentially reduce infarct volumes. Therefore, we administered TGFα or vehicle directly into the area surrounding the infarct in female mice that received gender-mismatched bone marrow transplants from green fluorescent protein (GFP)–expressing males prior to undergoing permanent middle cerebral artery occlusion. Newborn cells were tracked with bromodeoxyuridine (BrdU) labeling and immunohistochemistry at 90 days after stroke onset. We also studied the ingress of bone marrow–derived cells into the ischemic brain to determine whether such cells contribute to angiogenesis or neurogenesis. Infarct volumes were measured at 90 days poststroke. The results show that TGFα led to significant increments in the number of newborn neurons and glia in the ischemic hemisphere. TGFα also led to significant increments in the number of bone marrow–derived cells entering into the ischemic hemisphere. Most of these cells did not label with BrdU and represented endothelial cells that incorporated into blood vessels in the infarct border zone. Our results also show that infarct size was significantly reduced in animals treated with TGFα compared with controls. These results suggest that TGFα can induce angiogenesis, neurogenesis and neuroprotection after stroke. At least part of the pro-angiogenic effect appears to be secondary to the incorporation of bone marrow–derived endothelial cells into blood vessels in the infarct border zone.