Clinical significance of alphaII-spectrin breakdown products in cerebrospinal fluid after severe traumatic brain injury.
Following traumatic brain injury (TBI), the cytoskeletal protein alpha-II-spectrin is proteolyzed by calpain and caspase-3 to signature breakdown products. To determine whether alpha -II-spectrin proteolysis is a potentially reliable biomarker for TBI in humans, the present study (1) examined levels of spectrin breakdown products (SBDPs) in cerebrospinal fluid (CSF) from adults with severe TBI and (2) examined the relationship between these levels, severity of injury, and clinical outcome. This prospective case control study enrolled 41 patients with severe TBI, defined by a Glasgow Coma Scale (GCS) score of < or =8, who underwent intraventricular intracranial pressure monitoring. Patients without TBI requiring CSF drainage for other medical reasons served as controls. Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, and 120 h following TBI and analyzed for SBDPs. Outcome was assessed using the Glasgow Outcome Score (GOS) 6 months after injury. Calpain and caspase-3 mediated SBDP levels in CSF were significantly increased in TBI patients at several time points after injury, compared to control subjects. The time course of calpain mediated SBDP150 and SBDP145 differed from that of caspase-3 mediated SBDP120 during the post-injury period examined. Mean SBDP densitometry values measured early after injury correlated with severity of injury, computed tomography (CT) scan findings, and outcome at 6 months post-injury. Taken together, these results support that alpha -II-spectrin breakdown products are potentially useful biomarker of severe TBI in humans. Our data further suggests that both necrotic/oncotic and apoptotic cell death mechanisms are activated in humans following severe TBI, but with a different time course after injury.
Pineda
Jose A
JA
Center for Traumatic Brain Injury Studies, E.F and W.L. McKnight Brain Institute of the University of Florida, Gainesville, Florida, USA. Pineda_J@kids.wustl.edu
Lewis
Stephen B
SB
Valadka
Alex B
AB
Papa
Linda
L
Hannay
H Julia
HJ
Heaton
Shelley C
SC
Demery
Jason A
JA
Liu
Ming Cheng
MC
Aikman
Jada M
JM
Akle
Veronica
V
Brophy
Gretchen M
GM
Tepas
Joseph J
JJ
Wang
Kevin K W
KK
Robertson
Claudia S
CS
Hayes
Ronald L
RL
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000134:cerebrospinal fluid*; D002154:Calpain / Q000134:cerebrospinal fluid; D002352:Carrier Proteins / Q000134:cerebrospinal fluid*; D016022:Case-Control Studies; D053148:Caspase 3 / Q000134:cerebrospinal fluid; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D011446:Prospective Studies; D013049:Spectrin / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D002154:Calpain; D002352:Carrier Proteins; D053148:Caspase 3; D008840:Microfilament Proteins; D013049:Spectrin