Effect of bFGF on neuronal damage induced by sequential treatment of amyloid β and excitatory amino acid in vitro and in vivo.

Abstract Effects of basic fibroblast growth factor (bFGF), a potent neurotrophin, on neuronal damage induced by sequential treatment of amyloid β (Aβ) peptide and excitatory amino acid were examined in vitro and in vivo. Treatment of rat primary cortical neurons with glutamate (10 μM, 30 μM) resulted in neuronal damage, and pretreatment of the neurons with Aβ 25–35 (1.0 μM) at 48 h before glutamate stimulation augmented the susceptibility of the cells to the glutamate-induced neurotoxicity. Application of bFGF (0.3, 1, 3 ng/ml) and MK-801 (1, 3, 10, 30 nM) to the culture at 24 h before glutamate stimulation markedly decreased the neuronal damage elicited by Aβ 25–35 and glutamate. In a rat model of Alzheimer’s disease, in which aggregated Aβ 1–40 (4 μg/1 μl) was injected into the hippocampus, followed by an injection of ibotenate (an NMDA receptor agonist, 0.3 μg/0.5 μl) into the same sites at 48 h later, significant neuronal damage and learning deficit was induced. Administration of bFGF (25 ng/1 μl) into the hippocampus at 24 h before ibotenate inhibited the neuronal damage and demonstrated a trend of attenuating spatial learning deficits. These results suggest that bFGF might be a useful agent for treatment of Alzheimer’s disease in which Aβ peptide and glutamate would be involved as causative substances.