Biochemical Studies on Cerebrospinal Fluid in Patients With Unresponsive Wakefulness Syndrome: Toward a Potential Search for Biomarkers

Abstract Background: This study aimed to examine and screen patients for potential biomarkers for the diagnosis of unresponsive wakefulness syndrome (UWS). Methods: Patients with UWS, patients who regained consciousness (RC; patients in a minimally conscious state), and patients who had emerged from the minimally conscious state were evaluated using the Coma Recovery Scale-Revised (CRS-R). Cerebrospinal fluid (CSF) was collected from five healthy controls and 10 patients (5 UWS; 5 RC). Two-dimensional electrophoresis and proteomic analysis were used to examine and identify differentially expressed proteins in the CSF. Results: Compared with the control group, there were at least six proteins expressed at higher levels and two proteins expressed at lower levels in the CSF of the RC group than in the CSF of the UWS group. However, expression of vitamin D-binding protein (VDP) showed a further increase of 4.52-fold, that of DNA replication licensing factor mini-chromosome maintenance 4 (MCM4) showed a reduction of -20.61-fold, and that of hemoglobin subunit beta reversed to -8.34-fold in the UWS group. Another converse expression was of protein coenzyme Q-binding protein COQ10 homolog A (COQ10A), which was -4.31-fold in the RC group and 1.51-fold in the UWS group, compared to the control group. Expression of other proteins demonstrated an ascending trend in the RC group compared to the control group. Conclusions: The three differentially expressed proteins, VDP, DNA replication licensing factor MCM4, and hemoglobin subunit beta, may be involved in consciousness maintenance. This study identified potential biomarkers for UWS and will provide new insights into the pathogenesis of UWS.