Activin a release into cerebrospinal fluid in a subset of patients with severe traumatic brain injury.

Activin A is a member of the transforming growth factor-beta superfamily and has been demonstrated to be elevated during inflammation and to have neuroprotective properties following neural insults. In this study, we examined whether traumatic brain injury (TBI) induced a response in activin A or in the concentrations of its binding protein, follistatin. Thirty-nine patients with severe TBI had daily, matched cerebrospinal fluid (CSF) and serum samples collected post-TBI and these were assayed for activin A and follistatin using specific immunoassays. Concentrations of both molecules were assessed relative to a variety of clinical parameters, such as the Glasgow Coma Score, computer tomography classification of TBI, measurement of injury markers, cell metabolism and membrane breakdown products. In about half of the patients, there was a notable increase in CSF activin A concentrations in the first few days post-TBI. There were only minor perturbations in either serum activin or in either CSF or serum follistatin concentrations. The CSF activin A response was not related to any of the common TBI indices, but was strongly correlated with two common markers of brain damage, neuronal specific enolase and S100-beta. Further, activin A levels were also associated with indices of metabolism, such as lactate and pyruvate, excitotoxicity (glutamate) and membrane lipid breakdown products such as glycerol. In one of the two patients who developed a CSF infection, activin A concentrations in CSF became markedly elevated. Thus, some TBI patients have an early release of activin A into the CSF that may result from activation of inflammatory and/or neuroprotective pathways.

Activin A concentrations in human cerebrospinal fluid are age-dependent and elevated in meningitis.

OBJECTIVE: Activin A, and its binding protein, follistatin (FS), are expressed in the central nervous system (CNS). We have previously shown elevated concentrations of FS in the cerebrospinal fluid (CSF) of patients with meningitis and increased concentrations of activin A in the CSF of rabbits with bacterial meningitis. METHODS: We measured CSF and serum concentrations of activin A and FS in normal subjects and in patients with various neurological diseases using previously validated immunoassays specific for activin A or FS. RESULTS: In healthy persons, serum concentrations of both activin A and FS were age-dependent. In CSF, concentrations of activin A ranged from 0.03 to 0.33 ng/ml and were strongly correlated with age in both sexes, whereas FS CSF concentrations were below the assay detection limit in most of the patients. Activin A concentrations in CSF of patients with various neurological diseases, including meningitis, chronic inflammatory CNS diseases, neurodegenerative diseases, tumors in the CNS, cerebral ischemia, intracerebral/subarachnoid hemorrhages, subdural hemorrhages and epileptic seizures, were compared with age- and sex-matched control patients. The comparisons revealed significantly elevated concentrations of activin A in patients with meningitis (P=0.017). Serum concentrations of activin A or FS were not affected by any of the neurological diseases examined. CONCLUSIONS: Our results show for the first time that in normal subjects concentrations of activin A in CSF are correlated with age, and furthermore, that activin A CSF concentrations are elevated in patients with meningitis. The latter underlines a role for activin A in acute inflammatory processes within the CNS.