Stimulation of β2-Adrenoceptors Induces Nerve Growth Factor and Inhibits Apoptosis in Rat Brain After Ischemia

Abstract

Stimulation of β2-adrenoceptors in primary mixed cultures of rat hippocampai cells clearly protects neurons against glutamate-induced damage by an increased expression of nerve growth factor (NGF), since the neuroprotective effect of clenbuterol, a β2-adrenergic drug, was abolished, or at least reduced, by a β-blocker, NGF antibodies, p75 antibodies and NGF antisense oligodeoxynucleotide (ODN). Clenbuterol also reduced the infarct volume after occlusion of the middle cerebral artery in the rat and it decreased the number of damaged neurons after 10 min forebrain ischemia in the CA1 subfield of the rat. Simultaneously, the synthesis of NGF, as well as the synthesis of basic fibroblast growth factor (bFGF) and transforming growth factor-beta 1 (TGF-β1), was upregulated in various regions of the brain. In the rat model of global forebrain ischemia, DNA fragmentation and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells were diminished by clenbuterol, suggesting an anti-apoptotic potency of this drug. In addition, we could demonstrate an upregulation of the anti-apoptotic oncogenes Bcl-2 and Bcl-xl caused by clenbuterol, an effect, which could also contribute to the neuroprotection caused by stimulation of β2adrenoceptors.