Early dynamics of glial fibrillary acidic protein and extracellular DNA in plasma of mice after closed head traumatic brain injury

Abstract

Background: Glial fibrillary acidic protein (GFAP) in plasma is an established biomarker of traumatic brain injury (TBI) in humans. Plasma extracellular DNA (ecDNA) is a very sensitive, although nonspecific marker of tissue damage including TBI. Whether plasma GFAP or ecDNA could be used as an early non-invasive biomarker in the mouse model of closed head injury is unknown. The aim of this paper was to describe the early dynamics of plasma GFAP and ecDNA in the animal model of closed head TBI.

Methods: Closed head TBI was induced using the weight-drop method in 40 adult CD1 mice and blood was collected in different time points (1, 2 or 3h) after TBI in different groups of mice. Plasma GFAP and ecDNA and ecDNA fragmentation from the experimental groups were compared to healthy controls. In the surviving mice, a static rods test was performed 30 days after TBI to assess the neurological outcome of TBI.

Results: Despite a trend of higher plasma GFAP after TBI the differences between the groups were not statistically significant. Plasma ecDNA was higher by 50% after 1h (P<0.05) and 2h (P<0.05) after TBI and was highly variable after 3h. Plasma ecDNA, but not GFAP, was partially predictive of the neurological impairment of the mice.

Conclusion: In this study, we have described the early dynamics of plasma GFAP and ecDNA after TBI in mice. According to our results, ecDNA in plasma is a more sensitive early marker of TBI than GFAP. Analysis of tissue-specific ecDNA might improve its predictive value regarding the survival and neurobehavioral outcome.

Keywords: Cell-free DNA; Head injury; Neuroinflammation; Plasma DNA; Sterile inflammation.