Induction of activin A is essential for the neuroprotective action of basic fibroblast growth factor in vivo

Exogenous application of neurotrophic growth factors has emerged as a new a nd particularly promising approach not only to promote functional recovery after acute brain injury but also to protect neurons against the immediate effect of the injury. Among the various growth factors and cytokines studie d so far, the neuroprotective and neurotrophic profile of basic fibroblast growth factor (bFGF) Is the best documented(1-5). Using an animal model of acute excitotoxic brain injury(6), we report here that the neuroprotective action of bFGF, which is now being tested in stroke patients, depends on th e induction of activin A, a member of the transforming growth factor-beta s uperfamily. Our evidence for this previously unknown mechanism of action of bFGF is that bFGF strongly enhanced lesion-associated induction of activin A; in the presence of the activin-neutralizing protein follistatin, bFGF w as no longer capable of rescuing neurons from excitotoxic death; and recomb inant activin A exerted a neuroprotective effect by itself. Our data indica te that the development of substances influencing activin expression or rec eptor binding should offer new ways to fight neuronal loss in ischemic and traumatic brain injury.