Previously, we identified 14-3-3 beta and zeta
isoforms and proteolytic fragments of
alpha-spectrin as
proteins released from degenerating neurons that also rise markedly in cerebrospinal fluid (CSF) following experimental
brain injury or
ischemia in rodents, but these
proteins have not been studied before as potential
biomarkers for ischemic central nervous system injury in humans. Here we describe longitudinal analysis of these
proteins along with the neuron-enriched hypophosphorylated neurofilament H (pNFH) and the
deubiquitinating enzyme UCH-L1 in lumbar CSF samples from 19 surgical cases of
aortic aneurysm repair, 7 involving
cardiopulmonary bypass with
deep hypothermic circulatory arrest (DHCA). CSF levels of the
proteins were near the lower limit of detection by Western blot or
enzyme-linked fluorescence immunoassay at the onset of
surgical procedures, but increased substantially in a subset of cases, typically within 12-24 h. All cases involving DHCA were characterized by >3-fold elevations in CSF levels of the two 14-3-3
isoforms, UCH-L1, and pNFH. Six of 7 also exhibited marked increases in
alpha-spectrin fragments generated by
calpain, a
protease known to trigger necrotic neurodegeneration. Among cases involving aortic cross-clamping but not DHCA, the
proteins rose in CSF preferentially in the subset experiencing acute neurological complications. Our results suggest the neuron-enriched 14-3-3beta, 14-3-3zeta, pNFH, UCH-L1, and
calpain-cleaved
alpha-spectrin may serve as a panel of
biomarkers with clinical potential for the detection and management of ischemic central nervous system injury, including for mild damage associated with surgically-induced circulation arrest.