Endostatin/collagen XVIII is increased in cerebrospinal fluid after severe traumatic brain injury

Abstract

Recent studies have suggested that endogenous angiogenesis inhibitor endostatin/collagen XVIII might play an important role in the secondary brain injury following traumatic brain injury (TBI). In this study, we measured endostatin/collagen XVIII concentrations serially for 1 week after hospitalization by using the enzyme-linked immunosorbent assay method in the cerebrospinal fluid (CSF) of 30 patients with TBI and a Glasgow Coma Scale (GCS) score of 8 or less on admission. There was a significant trend toward increased CSF levels of endostatin after TBI versus control from 72 h after injury. In patients with GCS score of 3-5, CSF endostatin concentration was substantially higher at 72 h after injury than that in patients with GCS score of 6-8 (P < 0.05) and peaked rapidly at day 5 after injury, but decreased thereafter. The CSF endostatin concentration in 12 patients with an unfavorable outcome was significantly higher than that in 18 patients with a favorable outcome at day 5 (P = 0.043) and day 7 (P = 0.005) after trauma. Receiver operating characteristic curve analysis suggested a reliable operating point for the 7-day CSF endostatin concentration predicting poor prognosis to be 67.29 pg/mL. Our preliminary findings provide new evidence that endostatin/collagen XVIII concentration in the CSF increases substantially in patients with sTBI. Its dynamic change may have some clinical significance on the judgment of brain injury severity and the assessment of prognosis. This trial is registered with the ClinicalTrials.gov Identifier: NCT01846546.

Figure 1

Elevation of CSF endostatin/collagen XVIII concentrations following TBI at days 3, 5, and 7 but not day 1. (a) Bar graph showing the time course of endostatin/collagen XVIII concentrations in CSF of severe TBI patients 1 day, 3 days, 5 days, and 7 days after injury, compared with that in control patients without TBI. (b) Bar graph showing CSF endostatin/collagen XVIII concentrations in two GCS score groups on days 1, 3, 5, and 7 after injury. Each bar represents the mean and standard error of the mean of all samples over all time points. Statistical analysis was performed by Student's t-test or Mann-Whitney test. *P < 0.05 and **P < 0.01 compared with their respective controls.

Figure 2

Graphs showing correlations between endostatin/collagen XVIII concentrations in CSF and 1-month prognosis situation and 6-month outcome in the 30 study patients with severe TBI. Data are expressed as mean ± SEM values. *P < 0.05 and **P < 0.01 compared with their respective controls.

Figure 3

Receiver operating characteristic (ROC) curve to predict the possibility of unfavorable outcome at 6 months after trauma by measuring the CSF levels of endostatin/collagen XVIII. The value of 67.29 pg/mL at day 7 was considered the cutoff point, with the sensitivity and specificity of 75.0% and 83.3%, respectively.