Levels of F₂-isoprostanes, F₄-neuroprostanes, and total nitrate/nitrite in plasma and cerebrospinal fluid of patients with traumatic brain injury

Abstract

Several events occurring during the secondary damage of traumatic brain injury (TBI) can cause oxidative stress. F₂-isoprostanes (F₂-IsoPs) and F₄-neuroprostanes (F₄-NPs) are specific lipid peroxidation markers generated from arachidonic acid and docosahexaenoic acid, respectively. In this study, we evaluated oxidative stress in patients with moderate and severe TBI. Since sedatives are routinely used to treat TBI patients and propofol has been considered an antioxidant, TBI patients were randomly treated with propofol or midazolam for 72 h postoperation. We postoperatively collected cerebrospinal fluid (CSF) and plasma from 15 TBI patients for 6–10 d and a single specimen of CSF or plasma from 11 controls. Compared with the controls, the TBI patients exhibited elevated levels of F₂-IsoPs and F₄-NPs in CSF throughout the postsurgery period regardless of the sedative used. Compared with the group of patients who received midazolam, those who received propofol exhibited markedly augmented levels of plasma F₂-IsoPs, which were associated with higher F₄-NPs levels and lower total nitrate/nitrite levels in CSF early in the postsurgery period. Furthermore, the higher CSF F₂-IsoPs levels correlated with 6-month and 12-month worse outcomes, which were graded according to the Glasgow Outcome Scale. The results demonstrate enhanced oxidative damage in the brain of TBI patients and the association of higher CSF levels of F₂-IsoPs with a poor outcome. Moreover, propofol treatment might promote lipid peroxidation in the circulation, despite possibly suppressing nitric oxide or peroxynitrite levels in CSF, because of the increased loading of the lipid components from the propofol infusion.

Keywords::

• head injury
• lipid peroxidation
• sedative
• outcome
• nitric oxide

Declaration of interest

Authors report no declaration of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by grants (NSC 98-2314-B-182A-041-MY2 to Chih-Lung Lin, NSC 97-2320-B-182-012-MY3 to Hsiu-Chuan Yen, and NSC 95-2314-B-182-050-MY2 to Jee-Ching Hsu) from Ministry of Science and Technology (formerly known as National Science Council), Taiwan; and a grant from Chang Gung Memorial Hospital, Taiwan (CMRPD1B0341) to H.-C. Yen.

Supplementary material available online

Supplementary Figure 1–3 to be found online at http://informahealthcare.com/doi/abs/10.3109/10715762.2015.1080363.