Altered lipid metabolism as potential biomarker of poor outcome in sever traumatic brain injury (Pilot study)

2020 ◽  
Vol 40 ◽  
pp. 512-513
Author(s):  
V. Hancharou ◽  
V. Sviatlitskaya ◽  
S. Komlikau
Keyword(s):  
Traumatic Brain Injury ◽  
Lipid Metabolism ◽  
Brain Injury ◽  
Pilot Study ◽  
Poor Outcome ◽  
Potential Biomarker ◽  
Altered Lipid Metabolism ◽  
Altered Lipid

scholarly journals Traumatic Brain Injury Impairs Systemic Vascular Function Through Altered Lipid Metabolism and Disruption of Inward-Rectifier Potassium (Kir2.1) Channels

2021 ◽  
Author(s):  
Adrian M. Sackheim ◽  
Nuria Villalba ◽  
Maria Sancho ◽  
Osama F. Harraz ◽  
Adrian D. Bonev ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Smooth Muscle ◽  
Lipid Metabolism ◽  
Brain Injury ◽  
Smooth Muscle Cells ◽  
Inward Rectifier ◽  
Channel Function ◽  
Altered Lipid Metabolism ◽  
Altered Lipid ◽  
Kir2.1 Channel

AbstractBACKGROUND AND PURPOSETrauma can lead to widespread vascular endothelial dysfunction, but the underlying mechanisms remain largely unknown. Strong inward-rectifier potassium channels (Kir2.1) play a critical role in the dynamic regulation of regional perfusion and blood flow. Kir2.1 channel activity is modulated by phosphatidylinositol 4,5-bisphosphate (PIP2), a minor membrane phospholipid that is degraded by phospholipase A2 (PLA2) in conditions of oxidative stress or severe inflammation. We hypothesized that PLA2–induced depletion of PIP2 impairs Kir2.1 channel function.METHODSA fluid percussion injury model of traumatic brain injury (TBI) in rats was used to study mesenteric resistance arteries 24 hours after injury. Patch-clamp electrophysiology in freshly isolated endothelial and smooth muscle cells was performed to monitor Kir2.1 conductance, and the functional responses of intact arteries were assessed using pressure myography. We analyzed circulating PLA2, hydrogen peroxide (H2O2), and metabolites to identify alterations in signaling pathways associated with PIP2 in TBI.RESULTSElectrophysiology analysis of endothelial and smooth muscle cells revealed a significant reduction of Ba2+-sensitive Kir2.1 currents after TBI. Additionally, dilations to elevated extracellular potassium and BaCl2- or ML 133-induced constrictions in pressurized arteries were significantly decreased following TBI, consistent with an impairment of Kir2.1 channel function. The addition of a PIP2 analog to the patch pipette successfully rescued endothelial Kir2.1 currents after TBI. Both H2O2 and PLA2 activity were increased after injury. Metabolomics analysis demonstrated altered lipid metabolism signaling pathways, including increased arachidonic acid, and fatty acid mobilization after TBI.CONCLUSIONSOur findings support a model in which increased H2O2-induced PLA2 activity after trauma hydrolyzes endothelial PIP2, resulting in impaired Kir2.1 channel function.

IMPACT probability of poor outcome and plasma cytokine concentrations are associated with multiple organ dysfunction syndrome following traumatic brain injury

2019 ◽  
Vol 131 (6) ◽  
pp. 1931-1937 ◽  
Author(s):  
Sungho Lee ◽  
Hyunsoo Hwang ◽  
Jose-Miguel Yamal ◽  
J. Clay Goodman ◽  
Imoigele P. Aisiku ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Sofa Score ◽  
Plasma Concentrations ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Poor Outcome ◽  
Initial Plasma

OBJECTIVETraumatic brain injury (TBI) is a major cause of morbidity and mortality. Multiple organ dysfunction syndrome (MODS) occurs frequently after TBI and independently worsens outcome. The present study aimed to identify potential admission characteristics associated with post-TBI MODS.METHODSThe authors performed a secondary analysis of a recent randomized clinical trial studying the effects of erythropoietin and blood transfusion threshold on neurological recovery after TBI. Admission clinical, demographic, laboratory, and imaging parameters were used in a multivariable Cox regression analysis to identify independent risk factors for MODS following TBI, defined as maximum total Sequential Organ Failure Assessment (SOFA) score > 7 within 10 days of TBI.RESULTSTwo hundred patients were initially recruited and 166 were included in the final analysis. Respiratory dysfunction was the most common nonneurological organ system dysfunction, occurring in 62% of the patients. International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) probability of poor outcome at admission was significantly associated with MODS following TBI (odds ratio [OR] 8.88, 95% confidence interval [CI] 1.94–42.68, p < 0.05). However, more commonly used measures of TBI severity, such as the Glasgow Coma Scale, Injury Severity Scale, and Marshall classification, were not associated with post-TBI MODS. In addition, initial plasma concentrations of interleukin (IL)–6, IL-8, and IL-10 were significantly associated with the development of MODS (OR 1.47, 95% CI 1.20–1.80, p < 0.001 for IL-6; OR 1.26, 95% CI 1.01–1.58, p = 0.042 for IL-8; OR 1.77, 95% CI 1.24–2.53, p = 0.002 for IL-10) as well as individual organ dysfunction (SOFA component score ≥ 1). Finally, MODS following TBI was significantly associated with mortality (OR 5.95, 95% CI 2.18–19.14, p = 0.001), and SOFA score was significantly associated with poor outcome at 6 months (Glasgow Outcome Scale score < 4) when analyzed as a continuous variable (OR 1.21, 95% CI 1.06–1.40, p = 0.006).CONCLUSIONSAdmission IMPACT probability of poor outcome and initial plasma concentrations of IL-6, IL-8, and IL-10 were associated with MODS following TBI.

scholarly journals A-126 Clinical Utility of Risk Factors to Predict Self-reported Neurobehavioral Outcome Following Traumatic Brain Injury: PTSD, Sleep, Resilience, and Lifetime Blast Exposure

2020 ◽  
Vol 35 (6) ◽  
pp. 919-919
Author(s):  
Lange R ◽  
Lippa S ◽  
Hungerford L ◽  
Bailie J ◽  
French L ◽  
...  
Keyword(s):  
Risk Factors ◽  
Traumatic Brain Injury ◽  
Risk Factor ◽  
Brain Injury ◽  
Clinical Utility ◽  
Poor Sleep ◽  
Post Injury ◽  
Poor Outcome ◽  
Blast Exposure ◽  
Neurobehavioral Outcome

Abstract Objective To examine the clinical utility of PTSD, Sleep, Resilience, and Lifetime Blast Exposure as ‘Risk Factors’ for predicting poor neurobehavioral outcome following traumatic brain injury (TBI). Methods Participants were 993 service members/veterans evaluated following an uncomplicated mild TBI (MTBI), moderate–severe TBI (ModSevTBI), or injury without TBI (Injured Controls; IC); divided into three cohorts: (1) &lt; 12 months post-injury, n = 237 [107 MTBI, 71 ModSevTBI, 59 IC]; (2) 3-years post-injury, n = 370 [162 MTBI, 80 ModSevTBI, 128 IC]; and (3) 10-years post-injury, n = 386 [182 MTBI, 85 ModSevTBI, 119 IC]. Participants completed a 2-hour neurobehavioral test battery. Odds Ratios (OR) were calculated to determine whether the ‘Risk Factors’ could predict ‘Poor Outcome’ in each cohort separately. Sixteen Risk Factors were examined using all possible combinations of the four risk factor variables. Poor Outcome was defined as three or more low scores (&lt; 1SD) on five TBI-QOL scales (e.g., Fatigue, Depression). Results In all cohorts, the vast majority of risk factor combinations resulted in ORs that were ‘clinically meaningful’ (ORs &gt; 3.00; range = 3.15 to 32.63, all p’s &lt; .001). Risk factor combinations with the highest ORs in each cohort were PTSD (Cohort 1 & 2, ORs = 17.76 and 25.31), PTSD+Sleep (Cohort 1 & 2, ORs = 18.44 and 21.18), PTSD+Sleep+Resilience (Cohort 1, 2, & 3, ORs = 13.56, 14.04, and 20.08), Resilience (Cohort 3, OR = 32.63), and PTSD+Resilience (Cohort 3, OR = 24.74). Conclusions Singularly, or in combination, PTSD, Poor Sleep, and Low Resilience were strong predictors of poor outcome following TBI of all severities and injury without TBI. These variables may be valuable risk factors for targeted early interventions following injury.

Substance use on admission toxicology screen is associated with peri-injury factors and six-month outcome after traumatic brain injury: A TRACK-TBI Pilot study

2020 ◽  
Vol 75 ◽  
pp. 149-156
Author(s):  
John K. Yue ◽  
Ryan R.L. Phelps ◽  
Ethan A. Winkler ◽  
Hansen Deng ◽  
Pavan S. Upadhyayula ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Substance Use ◽  
Brain Injury ◽  
Pilot Study

scholarly journals The role of salivary vesicles as a potential inflammatory biomarker to detect traumatic brain injury in mixed martial artists

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rani Matuk ◽  
Mandy Pereira ◽  
Janette Baird ◽  
Mark Dooner ◽  
Yan Cheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Head Injury ◽  
Injury Severity ◽  
Expression Profiles ◽  
High Impact ◽  
Impact Mechanism ◽  
Inflammatory Biomarker ◽  
Potential Biomarker

AbstractTraumatic brain injury (TBI) is of significant concern in the realm of high impact contact sports, including mixed martial arts (MMA). Extracellular vesicles (EVs) travel between the brain and oral cavity and may be isolated from salivary samples as a noninvasive biomarker of TBI. Salivary EVs may highlight acute neurocognitive or neuropathological changes, which may be particularly useful as a biomarker in high impact sports. Pre and post-fight samples of saliva were isolated from 8 MMA fighters and 7 from controls. Real-time PCR of salivary EVs was done using the TaqMan Human Inflammatory array. Gene expression profiles were compared pre-fight to post-fight as well as pre-fight to controls. Largest signals were noted for fighters sustaining a loss by technical knockout (higher impact mechanism of injury) or a full match culminating in referee decision (longer length of fight), while smaller signals were noted for fighters winning by joint or choke submission (lower impact mechanism as well as less time). A correlation was observed between absolute gene information signals and fight related markers of head injury severity. Gene expression was also significantly different in MMA fighters pre-fight compared to controls. Our findings suggest that salivary EVs as a potential biomarker in the acute period following head injury to identify injury severity and can help elucidate pathophysiological processes involved in TBI.

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