Brain biomarkers and brain tissue oxygenation: changes and correlations following severe head injury

Introduction

This study evaluated relationships between CSF levels of brain biomarkers, glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase (UCH-L1) and α_II-spectrin breakdown (SBDP145), partial pressure of brain tissue oxygen (ptiO₂) and brain temperature (Licox system) during the first 24 hours and for up to 10 days following severe TBI.

Methods

We studied 27 severe TBI patients having CSF drainage and invasive monitoring of partial brain tissue oxygen tension (PbtO₂) and brain temperature using the Licox (Integra Neurosciences, Plainsboro, NJ, USA) probe. CSF SBDP145, UCH-L1 and GFAP levels were measured by quantitative ELISA assay on admission and every 6 hours thereafter for a maximum of 10 days. Using a double lumen bolt, ptiO₂ and temperature were measured with the Licox. This study focused on the recordings of the first 24 hours following injury (27 patients), as well as preliminary data from four patients for 10 days.

Results

The total duration of monitoring was 1,512 hours. During the first 24 hours, biomarker levels decreased while levels of PbrO₂ increased. All three biomarkers correlated with PbrO₂ (P < 0.0001, P = 0.016 and P = 0.023, respectively). After the first 24 hours, there were statistically significant changes in levels of brain biomarkers (SBDP145, UCH-L1 and GFAP) as well as in levels of ptiO₂ (respectively, P = 0.025, P < 0.0001, P = 0.033, P < 0.0001). However, the correlation between biomarkers and brain tissue oxygenation was sustained, and for UCH-L1 improved (P < 0.0001). No significant correlations between biomarker levels and brain temperature were found. There were no complications from the monitoring.

Conclusions

Our findings show that CFS levels of SBDP145, UCH-L1 and GFAP are related to brain tissue oxygenation in acute and possibly the subacute (≤10 days post injury) phases of severe TBI. Future studies will more directly address relationships between changes in tissue oxygenation and biochemical markers of injury following severe TBI. CSF levels of biomarkers and brain tissue oxygenation could yield insights into pathophysiological events following severe TBI and aid in clinical assessments of severe TBI patients.