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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:Purpose This study examined auditory deficits and symptom reporting in individuals with long-term postconcussion symptoms following a single mild traumatic brain injury (mTBI) compared to age- and gender-matched controls without a history of mTBI. Method Case history interviews, symptom questionnaires, and a battery of central auditory and neuropsychological tests were administered to 2 groups. The mTBI group was a civilian population recruited from a local concussion management program who were seeking rehabilitation for postconcussion-related problems in a postacute period between 3 and 18 months following injury. Symptom validity testing was included to assess the rate of possible insufficient test effort and its influence on scores for all outcome measures. Analyses of group differences in test scores were performed both with and without the participants who showed insufficient test effort. Rates of symptom reporting, correlations among symptoms and behavioral test outcomes, and the relationships between auditory and cognitive test performance were analyzed. Results The mTBI group reported a high rate of auditory symptoms and general postconcussion symptoms. Performance on neuropsychological tests of cognitive function showed some differences in raw scores between groups, but when effort was considered, there were no significant differences in the rate of abnormal performance between groups. In contrast, there were significant differences in both raw scores and the rate of abnormal performance between groups for some auditory tests when only considering participants with sufficient effort. Auditory symptoms were strongly correlated with other general postconcussion symptoms. Conclusions Significant auditory symptoms and evidence of long-term central auditory dysfunction were found in a subset of individuals who had chronic postconcussion symptoms after a single mTBI unrelated to blast trauma. The rate of abnormal performance on auditory behavioral tests exceeded the rate of abnormal performance on tests of cognitive function. Supplemental Material https://doi.org/10.23641/asha.8329955.

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.

Project description:Traumatic brain injury (TBI) can be serious partly due to the challenges of assessing and treating its neurocognitive and affective sequelae. The effects of a single TBI may persist for years and can limit patients' activities due to somatic complaints (headaches, vertigo, sleep disturbances, nausea, light or sound sensitivity), affective sequelae (post-traumatic depressive symptoms, anxiety, irritability, emotional instability) and mild cognitive impairment (MCI, including social cognition disturbances, attention deficits, information processing speed decreases, memory degradation and executive dysfunction). Despite a growing amount of research, study comparison and knowledge synthesis in this field are problematic due to TBI heterogeneity and factors like injury mechanism, age at or time since injury. The relative lack of standardization in neuropsychological assessment strategies for quantifying sequelae adds to these challenges, and the proper administration of neuropsychological testing relative to the relationship between TBI, MCI and neuroimaging has not been reviewed satisfactorily. Social cognition impairments after TBI (e.g., disturbed emotion recognition, theory of mind impairment, altered self-awareness) and their neuroimaging correlates have not been explored thoroughly. This review consolidates recent findings on the cognitive and affective consequences of TBI in relation to neuropsychological testing strategies, to neurobiological and neuroimaging correlates, and to patient age at and assessment time after injury. All cognitive domains recognized by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) are reviewed, including social cognition, complex attention, learning and memory, executive function, language and perceptual-motor function. Affect and effort are additionally discussed owing to their relationships to cognition and to their potentially confounding effects. Our findings highlight non-negligible cognitive and affective impairments following TBI, their gravity often increasing with injury severity. Future research should study (A) language, executive and perceptual-motor function (whose evolution post-TBI remains under-explored), (B) the effects of age at and time since injury, and (C) cognitive impairment severity as a function of injury severity. Such efforts should aim to develop and standardize batteries for cognitive subdomains-rather than only domains-with high ecological validity. Additionally, they should utilize multivariate techniques like factor analysis and related methods to clarify which cognitive subdomains or components are indeed measured by standardized tests.

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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