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Elevated Serum Levels of Inflammation-Related Cytokines in Mild Traumatic Brain Injury Are Associated With Cognitive Performance.

ABSTRACT: Mild traumatic brain injury (mTBI) is the most common neurological insult and leads to long-lasting cognitive impairments. The immune system modulates brain functions and plays a key role in cognitive deficits, however, the relationship between TBI-induced changes in inflammation-related cytokine levels and cognitive consequences is unclear. This was investigated in the present study in two cohorts of individuals within 1 week of mTBI (n = 52, n = 43) and 54 matched healthy control subjects. Patients with mTBI were also followed up at 1 and 3 months post-injury. Measures included cognitive assessments and a 9-plex panel of serum cytokines including interleukin (IL)-1?, IL-4, IL-6, IL-8, IL-10, IL-12, chemokine ligand 2 (CCL2), interferon-? (IFN-?), and tumor necrosis factor-? (TNF-?). The contribution of cytokine levels to cognitive function was evaluated by multivariate linear regression analysis. The results showed that serum levels of IL-1?, IL-6, and CCL2 were acutely elevated in mTBI patients relative to controls; CCL2 level was remained high over 3 months whereas IL-1? and IL-6 levels were declined by 3 months post-injury. A high level of CCL2 was associated with greater severity of post-concussion symptoms (which survived in the multiple testing correction); elevated IL-1? was associated with worse working memory in acute phase (which failed in correction); and acute high CCL2 level predicted higher information processing speed at 3 months post-injury (which failed in correction). Thus, acute serum cytokine levels are useful for evaluating post-concussion symptoms and predicting cognitive outcome in participants with mTBI.

SUBMITTER: Sun Y

PROVIDER: S-EPMC6819507 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Elevated Serum Levels of Inflammation-Related Cytokines in Mild Traumatic Brain Injury Are Associated With Cognitive Performance.

Sun Yingxiang Y Bai Lijun L Niu Xuan X Wang Zhuonan Z Yin Bo B Bai Guanghui G Zhang Danbin D Gan Shuoqiu S Sun Chuanzhu C Wang Shan S Zhu Feng F Zhang Ming M

Frontiers in neurology 20191023

Mild traumatic brain injury (mTBI) is the most common neurological insult and leads to long-lasting cognitive impairments. The immune system modulates brain functions and plays a key role in cognitive deficits, however, the relationship between TBI-induced changes in inflammation-related cytokine levels and cognitive consequences is unclear. This was investigated in the present study in two cohorts of individuals within 1 week of mTBI (<i>n</i> = 52, <i>n</i> = 43) and 54 matched healthy control ...[more]

PMID: 31708858

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Project description:Innate immune activation has been attributed a key role in traumatic brain injury (TBI) and successive morbidity. In mild TBI (mTBI), however, the extent and persistence of innate immune activation are unknown. We determined plasma cytokine level changes over 12 months after an mTBI in hospitalized and non-hospitalized patients compared with community controls; and examined their associations to injury-related and demographic variables at admission. Prospectively, 207 patients presenting to the emergency department (ED) or general practitioner with clinically confirmed mTBI and 82 matched community controls were included. Plasma samples were obtained at admission, after 2 weeks, 3 months, and 12 months. Cytokine levels were analysed with a 27-plex beads-based immunoassay. Brain magnetic resonance imaging (MRI) was performed on all participants. Twelve cytokines were reliably detected. Plasma levels of interferon gamma (IFN-γ), interleukin 8 (IL-8), eotaxin, macrophage inflammatory protein-1-beta (MIP-1β), monocyte chemoattractant protein 1 (MCP-1), IL-17A, IL-9, tumor necrosis factor (TNF), and basic fibroblast growth factor (FGF-basic) were significantly increased at all time-points in patients compared with controls, whereas IFN-γ-inducing protein 10 (IP-10), platelet-derived growth factor (PDGF), and IL-1ra were not. IL-17A and FGF-basic showed significant increases in patients from admission to follow-up at 3 months, and remained increased at 12 months compared with admission. Interestingly, MRI findings were negatively associated with four cytokines: eotaxin, MIP-1β, IL-9, and IP-10, whereas age was positively associated with nine cytokines: IL-8, eotaxin, MIP-1β, MCP-1, IL-17A, IL-9, TNF, FGF-basic, and IL-1ra. TNF was also increased in those with presence of other injuries. In conclusion, mTBI activated the innate immune system consistently and this is the first study to show that several inflammatory cytokines remain increased for up to 1 year post-injury.

Project description:Pathological mental fatigue after mild traumatic brain injury (TBI-MF) is characterized by pronounced mental fatigue after cognitive activity. The neurological origin is unknown, and we aimed in the present study to investigate how prolonged mental activity affects cognitive performance and its neural correlates in individuals with TBI-MF. We recruited individuals with TBI-MF (n = 20) at least 5 months after injury, and age-matched healthy controls (n = 20). We used functional near-infrared spectroscopy (fNIRS) to assess hemodynamic changes in the frontal cortex. The self-assessed mental energy level was measured with a visual analog scale (VAS) before and after the experimental procedure. A battery of six neuropsychological tests including Stroop-Simon, Symbol Search, Digit Span, Parallel Serial Mental Operation (PaSMO), Sustained Attention and Working Memory test, and Digit Symbol Coding (DSC) were used. The sequence was repeated once after an 8 min sustained-attention test. The test procedure lasted 2½ h. The experimental procedure resulted in a decrease in mental energy in the TBI-MF group, compared to controls (interaction, p < 0.001, ?p 2 = 0.331). The TBI-MF group performed at a similar level on both DSC tests, whereas the controls improved their performance in the second session (interaction, p < 0.01, ?p 2 = 0.268). During the Stroop-Simon test, the fNIRS event-related response showed no time effect. However, the TBI-MF group exhibited lower oxygenated hemoglobin (oxy-Hb) concentrations in the frontal polar area (FPA), ventrolateral motor cortex, and dorsolateral prefrontal cortex (DLPFC) from the beginning of the test session. A Stroop and Group interaction was found in the left ventrolateral prefrontal cortex showing that the TBI-MF group did have the same oxy-Hb concentration for both congruent and incongruent trials, whereas the controls had more oxy-Hb in the incongruent trial compared to the congruent trial (interaction, p < 0.01, ?p 2 = 0.227). In sum these results indicate that individuals with TBI-MF have a reduced ability to recruit the frontal cortex, which is correlated with self-reported mental fatigue. This may result both in deterioration of cognitive function and the experience of a mental fatigue after extended mental activity.

Dataset Information

Elevated Serum Levels of Inflammation-Related Cytokines in Mild Traumatic Brain Injury Are Associated With Cognitive Performance.

Publications

Elevated Serum Levels of Inflammation-Related Cytokines in Mild Traumatic Brain Injury Are Associated With Cognitive Performance.

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