Clenbuterol induces growth factor mRNA, activates astrocytes, and protects rat brain tissue against ischemic damage.
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.
Culmsee
C
C
Institut für Pharmakologie und Toxicologie, Philipps-Universität Marburg, FAchbereich Pharmazie, Germany.
Stumm
R K
RK
Schäfer
M K
MK
Weihe
E
E
Krieglstein
J
J
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002536:Cerebral Arteries / Q000601:surgery; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002976:Clenbuterol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017403:In Situ Hybridization; D007238:Infarction / Q000473:pathology; D007511:Ischemia / Q000473:pathology*; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
D001786:Blood Glucose; D005904:Glial Fibrillary Acidic Protein; D006133:Growth Substances; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D002976:Clenbuterol