Principal components derived from CSF inflammatory profiles predict outcome in survivors after severe traumatic brain injury

Kumar, Raj G.; Rubin, Jonathan E.; Berger, Rachel P.; Kochanek, Patrick M.; Wagner, Amy K.

doi:10.1016/j.bbi.2015.12.008

Cited by 45 publications

(34 citation statements)

References 43 publications

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“…Cytokine elevations in the brain tissue of rodents exposed to blast are well-established (Cho et al, 2013; Simard et al, 2014), as are central and peripheral cytokine elevations after clinical blunt-force trauma (Ferreira et al, 2014; Kumar et al, 2016; Plesnila, 2016; Santarsieri et al, 2015). However, there remains a gap in the knowledge surrounding inflammatory consequences of primary blast exposure in humans.…”

Section: Introductionmentioning

confidence: 99%

Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

Gill

Motamedi

Osier

et al. 2017

Brain, Behavior, and Immunity

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A unique cohort of military personnel exposed to isolated blast was studied to explore acute peripheral cytokine levels, with the aim of identifying blast-specific biomarkers. Several cytokines, including interleukin (IL) 6, IL-10 and tumor necrosis factor alpha (TNFα) have been linked to pre-clinical blast exposure, but remained unstudied in clinical blast exposure. To address this gap, blood samples from 62 military personnel were obtained at baseline, and daily, during a 10-day blast-related training program; changes in the peripheral concentrations of IL-6, IL-10 and TNFα were evaluated using an ultrasensitive assay. Two groups of trainees were matched on age, duration of military service, and previous history of blast exposure(s), resulting in moderate blast cases and no/low blast controls. Blast exposures were measured using helmet sensors that determined the average peak pressure in pounds per square inch (psi). Moderate blast cases had significantly elevated concentrations of IL-6 (F1,60 =18.81, p < 0.01) and TNFα (F1,60 =12.03, p < 0.01) compared to no/low blast controls; levels rebounded to baseline levels the day after blast. On the day of the moderate blast exposure, the extent of the overpressure (psi) in those exposed correlated with IL-6 (r = 0.46, p < 0.05) concentrations. These findings indicate that moderate primary blast exposure results in changes, specifically acute and transient increases in peripheral inflammatory markers which may have implications for neuronal health.

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Section: Introductionmentioning

confidence: 99%

Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

Gill

Motamedi

Osier

et al. 2017

Brain, Behavior, and Immunity

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“…STBI directly damage the brain. Injured neurons and local inflammatory cells release inflammatory cytokines, chemotactic factors (such as MCP-1), neurotransmitters and oxygen radicals (15). These promote the expression of adhesion molecules and cause damage to the vascular endothelium (15).…”

Section: Discussionmentioning

confidence: 99%

Lutein protects against severe traumatic brain injury through anti-inflammation and antioxidative effects via ICAM-1/Nrf-2

Tan

Chen

et al. 2017

Molecular Medicine Reports

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Many studies have reported that lutein may exert its biological activities, including anti-inflammation, anti-oxidase and anti-apoptosis, through effects on reactive oxygen species (ROS). Thus, lutein may prevent the damaging activities of ROS in cells. The current study investigated the effect of lutein against severe traumatic brain injury (STBI) and examined the mechanism of this protective effect. Sprague-Dawley rats were randomly divided into 5 groups: Control group, STBI model group, 40 mg/kg lutein-treated group, 80 mg/kg lutein-treated group and 160 mg/kg lutein-treated group. In this study, lutein protects against STBI, suppressed, interleukin (IL)-1β, IL-6 and monocyte chemoattractant protein-1 expression, reduced serum ROS levels, and reduced superoxide dismutase and glutathione peroxidase activities in STBI rats. Treatment with lutein effectively downregulated the expression of NF-κB p65 and cyclooxygenase-2, intercellular adhesion molecule (ICAM)-1 protein, and upregulated nuclear factor erythroid 2 like 2 (Nrf-2) and endothelin-1 protein levels in STBI rats. These findings demonstrated that lutein protects against STBI, has anti-inflammation and antioxidative effects and alters ICAM-1/Nrf-2 expression, which may be a novel therapeutic for STBI the clinic.

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“…Production of IL‐6 is upregulated in many chronic neuroinflammatory diseases (reviewed in (Rothaug, Becker‐Pauly, & Rose‐John, ; Spooren et al, )). For example, it is found at elevated levels in the CSF of patients with neuromyelitis optica (NMO; Uzawa et al, ; Uzawa et al, ), transverse myelitis (TM; Dixit et al, ; Kaplin et al, ; Wullschleger et al, ), acute disseminated encephalomyelitis (ADEM; Ishizu et al, ), ALS (Sekizawa et al, ), herpes simplex encephalitis (Aurelius, Andersson, Forsgren, Skoldenberg, & Strannegard, ; Kamei et al, ), Parkinson's disease (PD; Muller, Blum‐Degen, Przuntek, & Kuhn, ), traumatic brain injury (TBI; Kumar, Rubin, Berger, Kochanek, & Wagner, ), stroke (Tarkowski et al, ), and other diseases. Interestingly, there is strong evidence for a primary, causal role of IL‐6 in the pathogenesis of neuromyelitis optica spectrum disorders (NMOSD), such as NMO (Araki et al, ; Uzawa, Mori, Arai, et al, ) and TM (Dixit et al, ; Kaplin et al, ), which we will discuss in more detail here.…”

Section: Production Signaling and Effects Of Il‐6 And Ifn‐i In The Cnsmentioning

confidence: 99%

Microglia responses to interleukin‐6 and type I interferons in neuroinflammatory disease

West

Viengkhou

Campbell

et al. 2019

Glia

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Microglia are the resident macrophages of the central nervous system (CNS). They are a heterogenous, exquisitely responsive, and highly plastic cell population, which enables them to perform diverse roles. They sense and respond to the local production of many different signals, including an assorted range of cytokines. Microglia respond strongly to interleukin‐6 (IL‐6) and members of the type I interferon (IFN‐I) family, IFN‐alpha (IFN‐α), and IFN‐beta (IFN‐β). Although these cytokines are essential in maintaining homeostasis and for activating and regulating immune responses, their chronic production has been linked to the development of distinct human neurological diseases, termed “cerebral cytokinopathies.” IL‐6 and IFN‐α have been identified as key mediators in the pathogenesis of neuroinflammatory disorders including neuromyelitis optica and Aicardi‐Goutières syndrome, respectively, whereas IFN‐β has an emerging role as a causal factor in age‐associated cognitive decline. One of the key features that unites these diseases is the presence of highly reactive microglia. The current understanding is that microglia contribute to the development of cerebral cytokinopathies and represent an important therapeutic target. However, it remains to be resolved whether microglia have beneficial or detrimental effects. Here we review and discuss what is currently known about the microglial response to IL‐6 and IFN‐I, based on both animal models and clinical studies. Foundational knowledge regarding the microglial response to IL‐6 and IFN‐I is now being used to devise therapeutic strategies to ameliorate neuroinflammation and promote repair: either through targeting microglia, or by targeting the reduction of CNS levels or downstream biological pathways of IL‐6 or IFN‐I.

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Principal components derived from CSF inflammatory profiles predict outcome in survivors after severe traumatic brain injury

Cited by 45 publications

References 43 publications

Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

Lutein protects against severe traumatic brain injury through anti-inflammation and antioxidative effects via ICAM-1/Nrf-2

Microglia responses to interleukin‐6 and type I interferons in neuroinflammatory disease

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