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.
Phillips
David J
DJ
Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia. david.phillips@med.monash.edu.au
Nguyen
Phuong
P
Adamides
Alexios A
AA
Bye
Nicole
N
Rosenfeld
Jeffrey V
JV
Kossmann
Thomas
T
Vallance
Shirley
S
Murray
Lynnette
L
Morganti-Kossmann
Maria C
MC
D028341:Activins / Q000097:blood* / Q000134:cerebrospinal fluid*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001930:Brain Injuries / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D005260:Female; D038681:Follistatin / Q000097:blood / Q000134:cerebrospinal fluid; D018698:Glutamic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D005990:Glycerol / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D019344:Lactic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood / Q000134:cerebrospinal fluid; D010751:Phosphopyruvate Hydratase / Q000097:blood / Q000134:cerebrospinal fluid; D019289:Pyruvic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D011859:Radiography; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood / Q000134:cerebrospinal fluid; D015599:Trauma Severity Indices
D038681:Follistatin; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D028341:Activins; D019344:Lactic Acid; D018698:Glutamic Acid; D019289:Pyruvic Acid; D010751:Phosphopyruvate Hydratase; D005990:Glycerol