Serial serum leukocyte apoptosis levels as predictors of outcome in acute traumatic brain injury

Hung-Chen Wang, Tzu-Ming Yang, Yu-Jun Lin, Wu-Fu Chen, Jih-Tsun Ho, Yu-Tsai Lin, Aij-Lie Kwan, Cheng-Hsien Lu, Hung-Chen Wang, Tzu-Ming Yang, Yu-Jun Lin, Wu-Fu Chen, Jih-Tsun Ho, Yu-Tsai Lin, Aij-Lie Kwan, Cheng-Hsien Lu

Abstract

Background: Apoptosis associates with secondary brain injury after traumatic brain injury (TBI). This study posits that serum leukocyte apoptosis levels in acute TBI are predictive of outcome.

Methods: Two hundred and twenty-nine blood samples from 88 patients after acute TBI were obtained on admission and on Days 4 and 7. Serial apoptosis levels of different leukocyte subsets were examined in 88 TBI patients and 27 control subjects.

Results: The leukocyte apoptosis was significantly higher in TBI patients than in controls. Brief unconsciousness (P = 0.009), motor deficits (P ≤ 0.001), GCS (P ≤ 0.001), ISS (P = 0.001), WBC count (P = 0.015), late apoptosis in lymphocytes and monocytes on Day 1 (P = 0.004 and P = 0.022, resp.), subdural hemorrhage on initial brain CT (P = 0.002), neurosurgical intervention (P ≤ 0.001), and acute posttraumatic seizure (P = 0.046) were significant risk factors of outcome. Only motor deficits (P = 0.033) and late apoptosis in monocytes on Day 1 (P = 0.037) were independently associated with outcome. A cutoff value of 5.72% of late apoptosis in monocytes was associated with poor outcome in acute TBI patients.

Conclusion: There are varying degrees of apoptosis in patients following TBI and in healthy individuals. Such differential expression suggests that apoptosis in different leukocyte subsets plays an important role in outcome following injury.

Figures

Figure 1
Figure 1
Mean percentages of early apoptosis (annexin V) in (a) total leukocytes, (b) neutrophils, (c) lymphocytes, and (d) monocytes on Days 1, 4, and 7 in patients with acute TBI and in the controls. AP < 0.05, acute TBI patients with good outcome versus health controls; BP < 0.05, acute TBI patients with poor outcome versus health controls; *P < 0.05, acute TBI patients with poor outcome versus those with good outcome, by Mann-Whitney U test.
Figure 2
Figure 2
Mean percentages of mitochondrial apoptosis (APO2.7) in (a) total leukocytes, (b) neutrophils, (c) lymphocytes, and (d) monocytes on Days 1, 4, and 7 in patients with acute TBI and in the controls. AP < 0.05, acute TBI patients with good outcome versus health controls; BP < 0.05, acute TBI patients with poor outcome versus health controls; *P < 0.05, acute TBI patients with poor outcome versus those with good outcome, by Mann-Whitney U test.
Figure 3
Figure 3
Mean percentages of late apoptosis (annexin V+7-AAD) in (a) total leukocytes, (b) neutrophils, (c) lymphocytes, and (d) monocytes on Days 1, 4, and 7 in patients with acute TBI and in the controls. AP < 0.05, acute TBI patients with good outcome versus health controls; BP < 0.05, acute TBI patients with poor outcome versus health controls; *P < 0.05, acute TBI patients with poor outcome versus those with good outcome, by Mann-Whitney U test.

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