Clenbuterol induces growth factor mRNA, activates astrocytes, and protectsrat brain tissue against ischemic damage

The induction of growth factor synthesis in brain tissue by beta(2)-adrenoc eptor agonists, such as clenbuterol, is a promising approach to protect bra in tissue from ischemic damage. Clenbuterol (0.01-0.5 mg/kg) reduced the co rtical infarct volume in Long-Evans rats as measured 7 days after permanent occlusion of the middle cerebral artery. Dosages of clenbuterol higher tha n 1 mg/kg showed no cerebroprotective effect due to a decrease in blood pre ssure and an increase in plasma glucose level. The increase in the mRNA lev el of nerve growth factor (NGF), basic fibroblast growth factor (basic FGF) , and transforming growth factor-beta(1) (TGF-beta(1)) mRNA in cortical and hippocampal tissue occurred earlier after middle cerebral artery occlusion and was more pronounced in animals treated with clenbuterol than in contro ls. 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 a strocytes and that this could be the mechanism of clenbuterol-induced cereb roprotection after ischemia. (C) 1999 Elsevier Science B.V. All rights rese rved.