The induction of growth factor synthesis in brain tissue by beta2-adrenoceptor agonists, such as clenbuterol, is a promising approach to protect brain tissue from ischemic damage. Clenbuterol (0.01-0.5 mg/kg) reduced the cortical infarct volume in Long-Evans rats as measured 7 days after permanent occlusion of the middle cerebral artery. Dosages of clenbuterol higher than 1 mg/kg showed no cerebroprotective effect due to a decrease in blood pressure and an increase in plasma glucose level. The increase in the mRNA level of nerve growth factor (NGF), basic fibroblast growth factor (basic FGF), and transforming growth factor-beta1 (TGF-beta1) mRNA in cortical and hippocampal tissue occurred earlier after middle cerebral artery occlusion and was more pronounced in animals treated with clenbuterol than in controls. In addition, glial fibrillary acidic protein (GFAP) mRNA expression was enhanced in astrocytes 6 h after ischemia in clenbuterol-treated animals. The results suggest that growth factor synthesis is enhanced in activated astrocytes and that this could be the mechanism of clenbuterol-induced cerebroprotection after ischemia.