Abstract
Quinolinic acid, a macrophage/microglia-derived excitotoxin fulfills a plethora of functions such as neurotoxin, gliotoxin, and proinflammatory mediator, and it alters the integrity and cohesion of the blood-brain barrier in several pathophysiological states. Beta-trace protein (BTP), a monomeric glycoprotein, is known to indicate cerebrospinal fluid leakage. Thus, the prior aim of this study was to investigate whether BTP might non-invasively indicate quinolinic acid-induced impaired blood-brain barrier integrity. The research hypotheses were tested in three subsamples with different states of immune activation (patients with HCV-infection and interferon-α, patients with major depression, and healthy controls). BTP has also been described as a sensitive marker in detecting impaired renal function. Thus, the renal function has been considered. Our study results revealed highest quinolinic acid and highest BTP- levels in the subsample of patients with HCV in comparison with the other subsamples with lower or no immune activation (quinolinic acid: F = 21.027, p < 0.001 [ANOVA]; BTP: F = 6.792, p < 0.01 [ANOVA]). In addition, a two-step hierarchical linear regression model showed that significant predictors of BTP levels are quinolinic acid, glomerular filtration rate and age. The neurotoxin quinolinic acid may impair blood-brain barrier integrity. BTP might be a new non-invasive biomarker to indicate quinolinic acid-induced impaired blood-brain barrier integrity.
Highlights
To verify the hypothesis that Beta-trace protein (BTP) might be an innovative new non-invasive marker for quinolinic acid-induced impaired blood-brain barrier integrity, we examined the relations of quinolinic acid and BTP in three subsamples of our research project on quinolinic acid and kynurenine pathway[1,60,61]
In comparison to the sample with HCV infection and INF-αtherapy, the immune activation associated with major depression and the subsequent quinolinic acid levels were expected to be much lower in the sample of patients suffering from major depression
The ∆R2 = 0.077 is highly significant (p < 0.001), which means that the introduction of quinolinic acid to the model significantly improves the explanation of the variance of BTP
Summary
Quinolinic acid fulfills a plethora of physiological functions such as neurotoxin, gliotoxin, prooxidant molecule and proinflammatory mediator, and it alters the integrity and cohesion of the blood-brain barrier[26,27]. Brain-specific and one of the major polypeptide constituents of the cerebrospinal fluid, and its detection to identify a suspected cerebrospinal fluid leakage is a well-established diagnostic method[35]. The prior aim of this study was to evaluate for the first time whether BTP might be a new non-invasive immunological marker for quinolinic acid-induced impaired blood-brain barrier integrity. We tested our research hypothesis in three subsamples with different conditions of immune activation and subsequent expected different quinolinic acid levels. BTP has been described as a sensitive marker in detecting impaired renal function and serum levels of quinolinic acid increase with chronic kidney disease severity[28]. The renal function, including the glomerular filtration rate (GFR), were considered
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