Correlation between Mild Traumatic Brain Injury-Induced Inflammatory Cytokines and Emotional Symptom Traits: A Systematic Review.
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ABSTRACT:
SUBMITTER: Malik S
PROVIDER: S-EPMC8773760 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo evaluate diagnostic/prognostic implications of neurosensory testing during the subacute stage in patients with pediatric mild traumatic brain injury (pmTBI).SettingRecruitment from pediatric emergency department and urgent care clinics, assessment in a controlled environment.ParticipantsIn total, 146 pmTBI patients evaluated 7.4 ± 2.3 days and approximately 4 months postinjury; 104 age/sex-matched healthy controls (HCs) at equivalent time points.DesignProspective cohort study.Main measuresNeurosensory examination based on sequence of 10 established tests of vestibular-ocular, oculomotor, vestibulospinal, and visual functioning.ResultsThe amount of symptom provocation (positive change from pretest symptomatology) was significantly increased in pmTBI relative to HCs on every subtest 1 week postinjury, as were deficits in monocular accommodative amplitude and King-Devick Test errors. However, symptom provocation did not meaningfully alter diagnostic sensitivity/specificity relative to more easily obtained pretest symptom ratings. Evidence of clinically significant symptom provocation 1 week postinjury improved sensitivity (Δ = +12.9%) of identifying patients with persistent postconcussive symptoms 4 months postinjury on an independent symptom measure.ConclusionsThe diagnostic sensitivity/specificity of neurosensory testing in acutely concussed youth may be limited at 1 week postinjury as a function of natural recovery occurring in most emergency department cohorts. Neurosensory screening may have greater utility for identifying patients who experience delayed recovery.
| S-EPMC7335318 | biostudies-literature
Project description:BackgroundA proportion of patients with mild traumatic brain injury (mTBI) suffer long-term consequences, and the reasons behind this are still poorly understood. One factor that may affect outcomes is cognitive reserve, which is the brain's ability to maintain cognitive function despite injury. It is often assessed through educational level or premorbid IQ tests. This study aimed to explore whether there were differences in post-concussion symptoms and symptom resolution between patients with mTBI and minor orthopedic injuries one week and three months after injury. Additional aims were to explore the relationship between cognitive reserve and outcome, as well as functional connectivity according to resting state functional magnetic resonance imaging (rs-fMRI).MethodFifteen patients with mTBI and 15 controls with minor orthopedic injuries were recruited from the emergency department. Assessments, including Rivermead Post-Concussion Questionnaire (RPQ), neuropsychological testing, and rs-fMRI scans, were conducted on average 7 days (SD = 2) and 122 days (SD = 51) after injury.ResultsAt the first time point, significantly higher rates of post-concussion symptoms (U = 40.0, p = 0.003), state fatigue (U = 56.5, p = 0.014), and fatigability (U = 58.5, p = 0.025) were observed among the mTBI group than among the controls. However, after three months, only the difference in post-concussion symptoms remained significant (U = 27.0, p = 0.003). Improvement in post-concussion symptoms was found to be significantly correlated with cognitive reserve, but only in the mTBI group (Spearman's rho = -0.579, p = .038). Differences in the trajectory of recovery were also observed for fatigability between the two groups (U = 36.5, p = 0.015). Moreover, functional connectivity differences in the frontoparietal network were observed between the groups, and for mTBI patients, functional connectivity differences in an executive control network were observed over time.ConclusionThe findings of this pilot study suggest that mTBI, compared to minor orthopedic trauma, is associated to both functional connectivity changes in the brain and concussion-related symptoms. While there is improvement in these symptoms over time, a small subgroup with lower cognitive reserve appears to experience more persistent and possibly worsening symptoms over time. This, however, needs to be validated in larger studies.Trial registrationNCT05593172. Retrospectively registered.
| S-EPMC10731820 | biostudies-literature
Project description:Mild traumatic brain injuries (mTBIs) trigger a neuroinflammatory response, which leads to perturbations in the levels of inflammatory cytokines, resulting in a distinctive profile. A systematic review and meta-analysis were conducted to synthesize data related to levels of inflammatory cytokines in patients with mTBI. The electronic databases EMBASE, MEDLINE, and PUBMED were searched from January 2014 to December 12, 2021. A total of 5,138 articles were screened using a systematic approach based on the PRISMA and R-AMSTAR guidelines. Of these articles, 174 were selected for full-text review and 26 were included in the final analysis. The results of this study demonstrate that within 24 hours, patients with mTBI have significantly higher levels of Interleukin-6 (IL-6), Interleukin-1 Receptor Antagonist (IL-1RA), and Interferon-γ (IFN-γ) in blood, compared to healthy controls in majority of the included studies. Similarly one week following the injury, patients with mTBI have higher circulatory levels of Monocyte Chemoattractant Protein-1/C-C Motif Chemokine Ligand 2 (MCP-1/CCL2), compared to healthy controls in majority of the included studies. The results of the meta-analysis also confirmed these findings by demonstrating significantly elevated blood levels of IL-6, MCP-1/CCL2, and Interleukin-1 beta (IL-1β) in the mTBI population compared to healthy controls (p < 0.0001), particularly in the acute stages (<7 days). Furthermore, it was found that IL-6, Tumor Necrosis Factor-alpha (TNF-α), IL-1RA, IL-10, and MCP-1/CCL2 were associated with poor clinical outcomes following the mTBI. Finally, this research highlights the lack of consensus in the methodology of mTBI studies that measure inflammatory cytokines in the blood, and also provides direction for future mTBI research.
| S-EPMC10213278 | biostudies-literature
Project description:Despite pre-clinical evidence for the role of inflammation in traumatic brain injury (TBI), there is limited data on inflammatory biomarkers in mild TBI (mTBI). In this study, we describe the profile of plasma inflammatory cytokines and explore associations between these cytokines and neuropsychological outcomes after mTBI. Patients with mTBI with negative computed tomography and orthopedic injury (OI) controls without mTBI were prospectively recruited from emergency rooms at three trauma centers. Plasma inflammatory cytokine levels were measured from venous whole-blood samples that were collected at enrollment (within 24 h of injury) and at 6 months after injury. Neuropsychological tests were performed at 1 week, 1 month, 3 months, and 6 months after the injury. Multivariate regression analysis was performed to identify associations between inflammatory cytokines and neuropsychological outcomes. A total of 53 mTBI and 24 OI controls were included in this study. The majority of patients were male (62.3%), and injured in motor vehicle accidents (37.7%). Plasma interleukin (IL)-2 (p = 0.01) and IL-6 (p = 0.01) within 24 h post-injury were significantly higher for mTBI patients compared with OI controls. Elevated plasma IL-2 at 24 h was associated with more severe 1-week post-concussive symptoms (p = 0.001). At 6 months, elevated plasma IL-10 was associated with greater depression scores (p = 0.004) and more severe post-traumatic stress disorder (PTSD) symptoms (p = 0.001). Plasma cytokine levels (within 24 h and at 6 months post-injury) were significantly associated with early and late post-concussive symptoms, PTSD, and depression scores after mTBI. These results highlight the potential role of inflammation in the pathophysiology of post-traumatic symptoms after mTBI.
| S-EPMC7757539 | biostudies-literature
Project description:A single traumatic brain injury (TBI), even when mild (ie, concussion), can cause lasting consequences. Individuals with a history of chronic (>1-year prior) mild TBI have an increased risk of mood disturbances (eg, depression, suicide). This population also has lingering sleep alterations, including poor sleep quality and changes in sleep stage proportions. Given these sleep deficits, we aimed to test whether sleep-dependent emotional memory consolidation is reduced in this population. We utilized a mild TBI group (3.7 ± 2.9 years post injury) and an uninjured (non-TBI) population. Participants viewed negative and neutral images both before and after a 12-hour period containing sleep ("Sleep" group) or an equivalent period of time spent awake ("Wake" group). Participants rated images for valence/arousal at both sessions, and memory recognition was tested at session two. The TBI group had less rapid eye movement (REM), longer REM latency, and more sleep complaints. Sleep-dependent memory consolidation of nonemotional images was present in all participants. However, consolidation of negative images was only present in the non-TBI group. A lack of differentiation between the TBI Sleep and Wake groups was due to poor performance in the sleep group and, unexpectedly, enhanced performance in the wake group. Additionally, although the non-TBI participants habituated to negative images over a waking period, the TBI participants did not. We propose disrupted sleep- and wake-dependent emotional processing contributes to poor emotional outcomes following chronic, mild TBI. This work has broad implications, as roughly one-third of the US population will sustain a mild TBI during their lifetime.
| S-EPMC5806572 | biostudies-literature
Project description:BackgroundAdult patients with mild traumatic brain injury (mTBI) exhibit distinct phenotypes of emotional and cognitive functioning identified by latent profile analysis of clinical neuropsychological assessments. When discerned early after injury, these latent clinical profiles have been found to improve prediction of long-term outcomes from mTBI. The present study hypothesized that white matter (WM) microstructure is better preserved in an emotionally resilient mTBI phenotype compared with a neuropsychiatrically distressed mTBI phenotype.MethodsThe present study used diffusion magnetic resonance imaging to investigate and compare WM microstructure in major association, projection, and commissural tracts between the two phenotypes and over time. Diffusion magnetic resonance images from 172 patients with mTBI were analyzed to compute individual diffusion tensor imaging maps at 2 weeks and 6 months after injury.ResultsBy comparing the diffusion tensor imaging parameters between the two phenotypes at global, regional, and voxel levels, emotionally resilient patients were shown to have higher axial diffusivity compared with neuropsychiatrically distressed patients early after mTBI. Longitudinal analysis revealed greater compromise of WM microstructure in neuropsychiatrically distressed patients, with greater decrease of global axial diffusivity and more widespread decrease of regional axial diffusivity during the first 6 months after injury compared with emotionally resilient patients.ConclusionsThese results provide neuroimaging evidence of WM microstructural differences underpinning mTBI phenotypes identified from neuropsychological assessments and show differing longitudinal trajectories of these biological effects. These findings suggest that diffusion magnetic resonance imaging can provide short- and long-term imaging biomarkers of resilience.
| S-EPMC10065831 | biostudies-literature
Project description:BACKGROUND:Brain-derived neurotrophic factor (BDNF) is one of the most abundant neurotrophins in the adult brain, and it plays important roles in modulating synaptic plasticity and synaptogenesis. This study attempted to elucidate the role of the BDNF variant rs6265 in emotional symptoms following mild traumatic brain injury (mTBI). METHODS:To investigate the association between BDNF Val66Met polymorphism (rs6265) and emotional symptoms in mTBI patients, we recruited 192 mTBI patients and evaluated their Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) scores in the first and sixth week after mTBI. RESULTS:The patients carrying the T allele of rs6265 had significantly higher BAI scores in the first week following mTBI. In addition, the patients carrying the T allele also showed higher scores of BDI in the first week. In the gender-specific subgroup analysis, the male patients carrying the T allele of rs6265 had higher scores of both BAI and BDI in the first and sixth week. Meanwhile, female patients carrying the T allele also had significantly higher scores of BDI in the first week following mTBI. CONCLUSIONS:This study provides evidence for the association between the BDNF variant rs6265 and emotional symptoms following mTBI.
| S-EPMC5776765 | biostudies-literature
Project description:There is a subset of patients with mild traumatic brain injury (mTBI) who report persistent symptoms that impair their functioning and quality of life. Being able to predict which patients will experience prolonged symptom recovery would help clinicians target resources for clinical follow-up to those most in need, and would facilitate research to develop precision medicine treatments for mTBI. The purpose of this study was to investigate the predictors of symptom recovery in a prospective sample of emergency department trauma patients with either mTBI or non-mTBI injuries. Subjects were examined at several time points from within 72?h to 45 days post-injury. We quantified and compared the value of a variety of demographic, injury, and clinical assessment (symptom, neurocognitive) variables for predicting self-reported symptom duration in both mTBI (n?=?89) and trauma control (n?=?73) patients. Several injury-related and neuropsychological variables assessed acutely (< 72?h) post-injury predicted symptom duration, particularly loss of consciousness (mTBI group), acute somatic symptom burden (both groups), and acute reaction time (both groups), with reasonably good model fit when including all of these variables (area under the receiver operating characteristic curve [AUC]?=?0.76). Incorporating self-reported litigation involvement modestly increased prediction further (AUC?=?0.80). The results highlight the multifactorial nature of mTBI recovery, and injury recovery more generally, and the need to incorporate a variety of variables to achieve adequate prediction. Further research to improve this model and validate it in new and more diverse trauma samples will be useful to build a neurobiopsychosocial model of recovery that informs treatment development.
| S-EPMC5784791 | biostudies-literature
Project description:Diffusion tensor imaging (DTI) parameters can detect changes in the brain microstructure in mild traumatic brain injury (mTBI). Whether these parameter changes can predict neural functional recovery after mTBI is still relatively unknown. The present study aimed to investigate the radiological-prognostic correlation between these radiological parameters and learning and memory deficits using an in-house constructed rat model of mTBI. We established a rat model of diffuse axonal injury (DAI) at different injury levels, followed by magnetic resonance imaging at 6, 24, and 72 h, and 1, 2 weeks post injury, and randomly selected the rats for analysis of histopathology and learning and memory deficits. DTI parameters and β-amyloid precursor protein (β-APP) levels were obtained to estimate the extent of brain injury and the correlation with the times of crossing the safety platform as measured using a water maze test. The results revealed that fractional anisotropy (FA) was sensitive to axonal integrity. FA values of the corpus callosum in the injury groups decreased at all time points post injury, except in the mild injury group, which recovered to normal levels at 1 and 2 weeks post-injury. The neural function of the mild injury group recovered to normal compared with the normal control group. FA value, β-APP of corpus callosum in different groups at 24 h post injury showed obvious correlation with learning and memory deficits at the recovery stage (r=0.881, r=-0.931). In conclusion, DTI can reflect varying injury states of DAI over time with direct comparison to histopathology and could be used to predict the neural functional recovery at the early stage post-injury in a rat model.
| S-EPMC7664597 | biostudies-literature
Project description:BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) triggers a complex series of inflammatory responses that contribute to secondary tissue damage. The aim of this study was to investigate the effect of baicalein, a flavonoid possessing potent anti-inflammatory properties, on functional and histological outcomes and inflammatory cytokine expression, following TBI in rats. EXPERIMENTAL APPROACH: Rats subjected to controlled cortical impact injury were injected with baicalein (30 mg kg(-1)) or vehicle immediately after injury or daily for 4 days. Neurological status was evaluated using the rotarod, adhesive removal, modified neurological severity scores and beam walk tests. Contusion volume and neuronal degeneration were measured using cresyl violet and FluoroJade B (FJB) histochemistry. Levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) mRNA and protein were assessed by real-time quantitative reverse transcriptase-PCR, enzyme-linked immunosorbent assay and immunohistochemistry. KEY RESULTS: Single-dose and multiple-dose treatment with baicalein significantly improved functional recovery and reduced contusion volumes up to day 28 post-injury, although multiple-dose baicalein was the more effective treatment. Single-dose baicalein also significantly reduced the number of degenerating neurons (31%) on post-injury day 1 as indicated by FJB staining. These changes were associated with significantly decreased levels, at the contusion site, of TNF-alpha, IL-1 beta and IL-6 mRNA at 6 h, and cytokine protein on day 1 post-injury. CONCLUSIONS AND IMPLICATIONS: Post-injury treatment with baicalein improved functional and histological outcomes and reduced induction of proinflammatory cytokines in rat TBI. The neuroprotective effect of baicalein may be related to a decreased inflammatory response following the injury.
| S-EPMC2607198 | biostudies-other