Activin A is a growth factor composed of two betaA subunits belonging to the transforming growth factor beta (TGF-beta) superfamily of dimeric proteins. The biological activity of activin A is mediated by two different types of receptors, the type I (ARI and ARIB) and the type II receptors (ARII and ARIIB), and by two activin-binding proteins, follistatin and follistatin-related gene. These factors bind to activin A and thereby inhibit its biological effects. Activin A, its receptors, and binding proteins are widely distributed throughout the brain. Studies employing models of acute brain injury strongly implicate enhanced activin A expression as a common response to acute neuronal damage of various origins. Hypoxic/ischemic injury, mechanical irritation, and chemical damage of brain evoke a strong upregulation of activin A. Subsequent experimental studies have shown that activin A has a beneficial role to neuronal recovery and that, by activating different pathways, activin A has robust neuroprotective activities. Because activin A induction occurs early after brain injury, its measurement may provide a potential biochemical index of the presence, location, and extent of brain injury. This approach may also facilitate the diagnosis of subclinical lesions at stages when monitoring procedures are unable to detect brain lesion and furthermore establish a prognosis.