Cerebrospinal Fluid Endothelin-1 in Severe Traumatic Brain Injury

Dear Editor:

We read with great interest the article by Salonia and colleagues, which reported increased levels of endothelin-1 (ET-1) in the cerebrospinal fluid (CSF) of children with severe traumatic brain injury (TBI), in association with unfavorable outcome. ¹ The study was well conducted and the findings are intriguing. However, we wonder if the authors have considered the influence of the blood–CSF barrier (B-CSF-B) on the CSF level of ET-1.

ET-1 synthesis may be upregulated in cerebrovascular endothelium under pathological conditions. ² The origin of ET-1 beyond endothelia in the CSF is still underclarified. As acknowledged by Salonia and colleagues, it would be better to measure both local (CSF) and systemic (serum) levels of ET-1. In terms of this limitation, the altered levels of ET-1 in the CSF of subjects with TBI may arise primarily from the leakage of serum ET-1 into the CSF through damaged B-CSF-B in TBI. ³ To correct for the B-CSF-B damage, and not allow the leakage of serum proteins into the CSF to influence the measured CSF levels of ET-1, the CSF/plasma index of ET-1 can be calculated as follows: \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\usepackage{upgreek}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} \begin{align*}{\rm{CSF \ index \ of}} \ { \rm{ET - 1 }} = {\frac{\frac{\rm CSF \ level \ of \ ET-1} {\rm Plasmin \ level \ of \ ET-1}} {\frac{\rm CSF \ level \ of \ albumin}{\rm Plasma \ level \ of \ albumin}}} \end{align*} \end{document}

Only by doing this may the leakage of serum proteins into the CSF be adjusted to avoid the above-hypothesized confounding factor.

In summary, it is promising to find an increased level of ET-1 in the CSF of patients with severe TBI. Although the source of this elevation remains to be elucidated, the association of ET-1 with prognosis of TBI warrants more investigations.