Chronic Inflammation After Severe Traumatic Brain Injury

Kumar, Raj G.; Boles, Jennifer A.; Wagner, Amy K.

doi:10.1097/htr.0000000000000067

Cited by 142 publications

(87 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This observation of increased IL-6 after moderate blast exposure in humans is unique, and consistent with the pre-clinical evidence which suggest central and peripheral IL-6 activity occurs after primary blast exposure (Kamnaksh et al, 2011). Increased IL-6 after blast exposure may have clinical ramifications, since pre-clinical blast studies and clinical studies of blunt-force TBIs report associations between central and peripheral IL-6 levels and poor outcomes (Kumar et al, 2015a; Kumar et al, 2015b; Minambres et al, 2003; Yang et al, 2013). Established physiological consequences of elevated IL-6 include ultrastructural changes in endothelial cells (Vajtr et al, 2009) and neuroinflammation (Erta et al, 2012; Kumar et al, 2015b; Yang et al, 2013).…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

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

View full text Add to dashboard Cite

show abstract

“…Of interest, the identification of the acute phase protein C3 seems to be a promising candidate marker that is easily measured in human TBI biofluids. Recently, there has been increased interest in the inflammatory markers in neurotrauma that can be coupled with neural specific protein to constitute a panel of TBI markers; several of these inflammatory markers have shown to be elevated clinically after severe TBI (100). Similarly, identified structural proteins constitute an interesting set of markers to be assessed post-injury time points, since these protein families have been among grass root of acute TBI biomarkers (βII–αII spectrins, ankyrins) (101–104).…”

Section: Resultsmentioning

confidence: 99%

Neuroproteomics and Systems Biology Approach to Identify Temporal Biomarker Changes Post Experimental Traumatic Brain Injury in Rats

et al. 2016

Self Cite

View full text Add to dashboard Cite

Traumatic brain injury (TBI) represents a critical health problem of which diagnosis, management, and treatment remain challenging. TBI is a contributing factor in approximately one-third of all injury-related deaths in the United States. The Centers for Disease Control and Prevention estimate that 1.7 million people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics–systems biology is proving to be a prominent tool in biomarker discovery for central nervous system injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI) model of experimental TBI in rat model to assess the temporal–global proteome changes after acute (1 day) and for the first time, subacute (7 days), post-injury time frame using the established cation–anion exchange chromatography-1D SDS gel electrophoresis LC–MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entity, we used in silico systems biology approach to understand the global dynamics that govern proteins that are differentially altered post-injury. In addition, gene ontology analysis of the proteomic data was conducted in order to categorize the proteins by molecular function, biological process, and cellular localization. Results show alterations in several proteins related to inflammatory responses and oxidative stress in both acute (1 day) and subacute (7 days) periods post-TBI. Moreover, results suggest a differential upregulation of neuroprotective proteins at 7 days post-CCI involved in cellular functions such as neurite growth, regeneration, and axonal guidance. Our study is among the first to assess temporal neuroproteome changes in the CCI model. Data presented here unveil potential neural biomarkers and therapeutic targets that could be used for diagnosis, for treatment and, most importantly, for temporal prognostic assessment following brain injury. Of interest, this work relies on in silico bioinformatics approach to draw its conclusion; further work is conducted for functional studies to validate and confirm the omics data obtained.

show abstract

“…Few studies investigated the cytokines blood levels during periods longer than 7 days (38, 39), and one report (40) investigated cytokines serum levels 3–6 months after the TBI.…”

Section: Discussionmentioning

confidence: 99%

“…A small number of studies have investigated inflammatory factors during slightly longer periods such as 7 days (36, 37), 14 days (38), or 22 days (39). Only one study (40) has reported elevated serum levels of IL-1β, IL-6, IL-8, IL-10, and TNF-α in TBI patients’ blood samples taken during the subacute and the chronic phase (3–6 months) after the injury.…”

Section: Introductionmentioning

confidence: 99%

Peripheral Inflammatory Markers and Antioxidant Response during the Post-Acute and Chronic Phase after Severe Traumatic Brain Injury

et al. 2016

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is a mechanical insult to the brain caused by external forces and associated with inflammation and oxidative stress. The patients may show different profiles of neurological recovery and a combination of oxidative damage and inflammatory processes can affect their courses. It is known that an overexpression of cytokines can be seen in peripheral blood in the early hours/days after the injury, but little is known about the weeks and months encompassing the post-acute and chronic phases. In addition, no information is available about the antioxidant responses mediated by the major enzymes that regulate reactive oxygen species levels: superoxide dismutase, catalase, peroxidases, and GSH-related enzymes. This study investigates the 6-month trends of inflammatory markers and antioxidant responses in 22 severe TBI patients with prolonged disorders of consciousness, consecutively recruited in a dedicated neurorehabilitation facility. Patients with a high degree of neurological impairment often show an uncertain outcome. In addition, the profiles of plasma activities were related to the neurological recovery after 12 months. Venous peripheral blood samples were taken blindly as soon as clinical signs and laboratory markers confirmed the absence of infections, 3 and 6 months later. The clinical and neuropsychological assessment continued up to 12 months. Nineteen patients completed the follow-up. In the chronic phase, persistent high plasma levels of cytokines can interfere with cognitive functioning and higher post-acute levels of cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL1b, IL6] are associated with poorer cognitive recoveries 12 months later. Moreover, higher IFN-γ, higher TNF-α, and lower glutathione peroxidase activity are associated with greater disability. The results add evidence of persistent inflammatory response, provide information about long-term imbalance of antioxidant activity, and suggest that the over-production of cytokines and the alteration of the redox homeostasis in the post-acute phase might adversely affect the neurological and functional recovery. Inflammatory and antioxidant activity markers might offer a feasible way to highlight some of the processes opposing recovery after a severe TBI.

show abstract

Chronic Inflammation After Severe Traumatic Brain Injury

Cited by 142 publications

References 23 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

Neuroproteomics and Systems Biology Approach to Identify Temporal Biomarker Changes Post Experimental Traumatic Brain Injury in Rats

Peripheral Inflammatory Markers and Antioxidant Response during the Post-Acute and Chronic Phase after Severe Traumatic Brain Injury

Contact Info

Product

Resources

About