Research Reports - Post-traumatic hypoxia is associated with prolonged cerebral cytokine production, higher serum biomarker levels and poor outcome in patients with severe traumatic brain injury

J Neurotrauma. 2013 Nov 26

Yan E, Satgunaseelan L, Paul E, Bye N, Nguyen P, Agyapomaa D, Kossmann T, Rosenfeld JV, Morganti-Kossmann C Ph D

Secondary hypoxia is a known contributor to adverse outcome in patients with
traumatic brain injury (TBI). Based on the evidence that hypoxia and TBI in
isolation induce neuroinflammation, we investigated whether TBI combined with
hypoxia enhances cerebral cytokine production. We also explored whether increased
concentrations of injury biomarkers discriminate between hypoxic and normoxic
patients, correlate to worse outcome, and depend on blood-brain barrier (BBB)
dysfunction. Forty-two TBI patients with Glasgow Coma Scale ≤8 were recruited.
Cerebrospinal fluid (CSF) and serum were collected over 6 days. Patients were
divided into hypoxic (Hx; n=22) and normoxic (Nx; n=20) groups. Eight cytokines
were measured in CSF; albumin, S100, MBP and NSE were quantified in serum.
CSF/serum albumin quotient was calculated for BBB function. Glasgow Outcome Scale
Extended was assessed at 6 months post-TBI. Production of GM-CSF was higher, and
profiles of GM-CSF, IFN-γ and to a lesser extent TNF, were prolonged in CSF of Hx
but not Nx patients at 4-5 days post-TBI. IL-2, IL-4, IL-6, IL-10 increased
similarly in both Hx and Nx groups. S100, MBP and NSE were significantly higher
in Hx patients with unfavourable outcome. Amongst these three biomarkers, S100
showed strongest correlations to GOSE after TBI-Hx. Elevated CSF/serum albumin
quotients lasted for 5 days post-TBI and displayed similar profiles in Hx and Nx
patients. We demonstrate for the first time that post-TBI hypoxia is associated
with prolonged neuroinflammation, amplified extravasation of biomarkers, and poor
outcome. S100 and MBP could be implemented to track the occurrence of post-TBI
hypoxia and prompt adequate treatment. Keywords: traumatic brain injury, hypoxia,
inflammation, biomarker, CSF/serum-albumin quotient.

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