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 and 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 studied so far, the neuroprotective and neurotrophic profile of basic fibroblast growth factor (bFGF) is the best documented. Using an animal model of acute excitotoxic brain injury, we report here that the neuroprotective action of bFGF, which is now being tested in stroke patients, depends on the induction of activin A, a member of the transforming growth factor-beta superfamily. 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 was no longer capable of rescuing neurons from excitotoxic death; and recombinant activin A exerted a neuroprotective effect by itself. Our data indicate that the development of substances influencing activin expression or receptor binding should offer new ways to fight neuronal loss in ischemic and traumatic brain injury.
Tretter
Y P
YP
Department of Physiology, University of Munich, Pettenkoferstr.12, D-80336 München, Germany.
Hertel
M
M
Munz
B
B
ten Bruggencate
G
G
Werner
S
S
Alzheimer
C
C
D028341:Activins; D000818:Animals; D001921:Brain / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D006133:Growth Substances / Q000096:biosynthesis* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D007265:Inhibins / Q000096:biosynthesis* / Q000494:pharmacology; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*
D006133:Growth Substances; D018696:Neuroprotective Agents; D016222:Fibroblast Growth Factor 2; D028341:Activins; D007265:Inhibins; D007608:Kainic Acid