scholarly journals NETs Lead to Sympathetic Hyperactivity After Traumatic Brain Injury Through the LL37-Hippo/MST1 Pathway

2021 ◽  
Vol 15 ◽  
Author(s):  
Kaixin Zhu ◽  
Yibai Zhu ◽  
Xiaoxiang Hou ◽  
Wen Chen ◽  
Xiaolin Qu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Flow Cytometry ◽  
Brain Injury ◽  
Diffuse Axonal Injury ◽  
Arginine Deiminase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Mortality And Morbidity ◽  
Sympathetic Hyperactivity ◽  
Expression Levels

Background: Paroxysmal sympathetic hyperactivity (PSH) is one of the important reasons for the high mortality and morbidity of traumatic brain injury (TBI). We aim to explore the role of the neutrophil extracellular traps (NETs) in the pathogenesis of sympathetic hyperexcitability after TBI and the underlying mechanisms, providing evidence for clinical treatment.Methods: Enzyme-linked immunosorbent assay was used to assess the plasma metanephrine and normetanephrine levels which represented the variation of the sympathetic system after TBI with rat diffuse axonal injury (DAI) model. NETs in the paraventricular nucleus (PVN) and circulating blood were examined using immunofluorescence and flow cytometry. Neutrophils-microglia co-culture system was established to further explore the effect of NETs on PSH and its mechanisms.Results: After TBI, metanephrine and normetanephrine levels began to increase at 9 h and peaked at 72 h. After the injury, the level of NETs kept increasing at 24 and 72 h in the PVN. A positive correlation was found between the concentration of the PVN NETs and blood catecholamine. Flow cytometry of peripheral blood cells revealed that NETs level in the injury group was higher than that in the control group. Immunofluorescence results confirmed the presence of NETs in the PVN after TBI. The positive result of immunoprecipitation suggested a correlation effect between LL37 and P2 × 7. Peptidyl arginine deiminase-4 (PAD4) inhibitor could inhibit the expression levels of MST1, YAP, and IL-1β. The hippo/MST1 pathway inhibitor could inhibit the expression levels of YAP and IL-1β.Conclusion: NETs formation in the PVN might be associated with sympathetic hyperactivity after TBI, which might relate to the activation of microglia cells and increased secretion of IL-1β via the hippo/MST1 pathway.

scholarly journals The preventive effect of dexmedetomidine on paroxysmal sympathetic hyperactivity in severe traumatic brain injury patients who have undergone surgery: a retrospective study

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2986 ◽  
Author(s):  
Qilin Tang ◽  
Xiang Wu ◽  
Weiji Weng ◽  
Hongpeng Li ◽  
Junfeng Feng ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Severe Traumatic Brain Injury ◽  
Control Group ◽  
Therapeutic Effects ◽  
Preventive Effect ◽  
Sympathetic Hyperactivity ◽  
Paroxysmal Sympathetic Hyperactivity ◽  
Hospital Stays ◽  
The Difference

BackgroundParoxysmal sympathetic hyperactivity (PSH) results and aggravates in secondary brain injury, which seriously affects the prognosis of severe traumatic brain injury patients. Although several studies have focused on the treatment of PSH, few have concentrated on its prevention.MethodsNinety post-operation (post-op) severe traumatic brain injury (sTBI) patients admitted from October 2014 to April 2016 were chosen to participate in this study. Fifty of the post-op sTBI patients were sedated with dexmedetomidine and were referred as the “dexmedetomidine group” (admitted from May 2015 to April 2016). The other 40 patients (admitted from October 2014 to May 2015) received other sedations and were referred as the “control group.” The two groups were then compared based on their PSH scores and the scores and ratios of those patients who met the criteria of “probable,” “possible” and “unlikely” using the PSH assessment measure (PSH-AM) designed by Baguley et al. (2014). The durations of the neurosurgery intensive care unit (NICU) and hospital stays and the Glasgow outcome scale (GOS) values for the two groups were also compared to evaluate the therapeutic effects and the patients’ prognosis.ResultsThe overall PSH score for the dexmedetomidine group was 5.26 ± 4.66, compared with 8.58 ± 8.09 for the control group. The difference between the two groups’ PSH scores was significant (P = 0.017). The score of the patients who met the criterion of “probable” was 18.33 ± 1.53 in the dexmedetomidine group and 22.63 ± 2.97 in the control group, and the difference was statistically significant (P = 0.045). The ratio of patients who were classified as “unlikely” between the two groups was statistically significant (P = 0.028); that is, 42 (84%) in the dexmedetomidine group and 25 (62.5%) in the control group. The differences in NICU, hospital stays and GOS values between the two groups were not significant.ConclusionDexmedetomidine has a preventive effect on PSH in sTBI patients who have undergone surgery.

Monitoring of brain interstitial total tau and beta amyloid proteins by microdialysis in patients with traumatic brain injury

2009 ◽  
Vol 110 (6) ◽  
pp. 1227-1237 ◽  
Author(s):  
Niklas Marklund ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
Elisabeth Ronne-Engström ◽  
Per Enblad ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Focal Lesion ◽  
Intracerebral Microdialysis ◽  
Metabolic Markers ◽  
Total Tau ◽  
T Tau

Object Damage to axons contributes to postinjury disabilities and is commonly observed following traumatic brain injury (TBI). Traumatic brain injury is an important environmental risk factor for the development of Alzheimer disease (AD). In the present feasibility study, the aim was to use intracerebral microdialysis catheters with a high molecular cutoff membrane (100 kD) to harvest interstitial total tau (T-tau) and amyloid beta 1–42 (Aβ42) proteins, which are important biomarkers for axonal injury and for AD, following moderate-to-severe TBI. Methods Eight patients (5 men and 3 women) were included in the study; 5 of the patients had a focal/mixed TBI and 3 had a diffuse axonal injury (DAI). Following the bedside analysis of the routinely measured energy metabolic markers (that is, glucose, lactate/pyruvate ratio, glycerol, and glutamate), the remaining dialysate was pooled and two 12-hour samples per day were used to analyze T-tau and Aβ42 by enzyme-linked immunosorbent assay from Day 1 up to 8 days postinjury. Results The results show high levels of interstitial T-tau and Aβ42 postinjury. Patients with a predominantly focal lesion had higher interstitial T-tau levels than in the DAI group from Days 1 to 3 postinjury (p < 0.05). In contrast, patients with DAI had consistently higher Aβ42 levels when compared with patients with focal injury. Conclusions These results suggest that monitoring of interstitial T-tau and Aβ42 by using microdialysis may be an important tool when evaluating the presence and role of axonal injury following TBI.

scholarly journals Neutrophil Extracellular Traps Facilitate Sympathoexcitation After Traumatic Brain Injury Via HMGB1/AP1 Signaling Pathway

2021 ◽  
Author(s):  
Kaixin Zhu ◽  
Xiaoxiang Hou ◽  
Xiaolin Qu ◽  
Wen Chen ◽  
Kun Chen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Diffuse Axonal Injury ◽  
Neutrophil Extracellular Traps ◽  
Control Group ◽  
Extracellular Traps ◽  
Important Form

Abstract Background: Traumatic brain injury (TBI) usually accompanies with sympathetic excitation, and paradoxical sympathetic hyperactivity (PSH) may be detrimental to the prognosis of TBI sufferers. Neutrophils can form neutrophil extracellular traps (NETs) to get involved in the neuroinflammation after TBI. As an important form of NETs, HMGB1 were found to activate the expression of AP1, which can increase the formation of IL-1β in microglia. Considering that IL-1β is able to regulate sympathoexcitation, it is reasonable to infer that HMGB1/AP1 signaling plays an important role in sympathoexcitation after TBI. Methods: In this present study, rat model with diffuse axonal injury (DAI) was established. The existance of NETs and the expression level of HMGB1/AP1/IL-1β in the paraventricular nucleus (PVN) after DAI were examined by immunofluorescence and Western blot (WB). The role of HMGB1/AP1 in the activation of microglia, secretion of IL-1β and sympathoexcitaiton were identified in vitro. Moreover, stereotaxic injection of anti-HMGB1 or HMGB1 was conducted to further validate the effect of HMGB1/AP1 pathway on sympathoexcitation after TBI.Results: The indicators of sympathoexcitation, including mean arterial pressure and serum catecholamine, increased and peaked at 72 hours after TBI. The formation of NETs was observed in PVN after injury, whereas, no NETs were found in the control group. And meanwhile, levels of NETs in PVN were higher than that in the para-PVN tissues after the injury. In vitro experiments showed that HMGB1 can promote the activation of microglia as well as increase the expression of AP1 and IL-1β. In vivo experiments suggested HMGB1 have an impact on the expression of AP1 and IL-1β in the PVN, and further controlling the sympathoexcitation after TBI.Conclusion: NETs might mediate sympathoexcitation after TBI through microglial activation in the PVN in a HMGB1/AP1/IL-1β dependent way.

Oxidative Stress: Major Threat in Traumatic Brain Injury

2018 ◽  
Vol 17 (9) ◽  
pp. 689-695 ◽  
Author(s):  
Nidhi Khatri ◽  
Manisha Thakur ◽  
Vikas Pareek ◽  
Sandeep Kumar ◽  
Sunil Sharma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mitochondrial Dysfunction ◽  
Calcium Influx ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Physical Assault ◽  
Mortality And Morbidity ◽  
Primary Injury

Background & Objective: Traumatic Brain Injury (TBI) is one of the major causes of mortality and morbidity worldwide. It represents mild, moderate and severe effects of physical assault to brain which may cause sequential, primary or secondary ramifications. Primary injury can be due to the first physical hit, blow or jolt to one of the brain compartments. The primary injury is then followed by secondary injury which leads to biochemical, cellular, and physiological changes like blood brain barrier disruption, inflammation, excitotoxicity, necrosis, apoptosis, mitochondrial dysfunction and generation of oxidative stress. Apart from this, there is also an immediate increase in glutamate at the synapses following severe TBI. Excessive glutamate at synapses in turn activates corresponding NMDA and AMPA receptors that facilitate excessive calcium influx into the neuronal cells. This leads to the generation of oxidative stress which further leads to mitochondrial dysfunction, lipid peroxidation and oxidation of proteins and DNA. As a consequence, neuronal cell death takes place and ultimately people start facing some serious disabilies. Conclusion: In the present review we provide extensive overview of the role of reactive oxygen species (ROS)-induced oxidative stress and its fatal effects on brain after TBI.

scholarly journals Remotely delivered environmental enrichment intervention for traumatic brain injury: Study protocol for a randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e039767
Author(s):  
Zorry Belchev ◽  
Mary Ellene Boulos ◽  
Julia Rybkina ◽  
Kadeen Johns ◽  
Eliyas Jeffay ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Active Control ◽  
Environmental Enrichment ◽  
Spatial Navigation ◽  
Controlled Trial ◽  
Control Group ◽  
Hippocampal Atrophy ◽  
Active Control Group ◽  
Navigation Group

IntroductionIndividuals with moderate-severe traumatic brain injury (m-sTBI) experience progressive brain and behavioural declines in the chronic stages of injury. Longitudinal studies found that a majority of patients with m-sTBI exhibit significant hippocampal atrophy from 5 to 12 months post-injury, associated with decreased cognitive environmental enrichment (EE). Encouragingly, engaging in EE has been shown to lead to neural improvements, suggesting it is a promising avenue for offsetting hippocampal neurodegeneration in m-sTBI. Allocentric spatial navigation (ie, flexible, bird’s eye view approach), is a good candidate for EE in m-sTBI because it is associated with hippocampal activation and reduced ageing-related volume loss. Efficacy of EE requires intensive daily training, prohibitive within most current health delivery systems. The present protocol is a novel, remotely delivered and self-administered intervention designed to harness principles from EE and allocentric spatial navigation to offset hippocampal atrophy and potentially improve hippocampal functions such as navigation and memory for patients with m-sTBI.Methods and analysisEighty-four participants with chronic m-sTBI are being recruited from an urban rehabilitation hospital and randomised into a 16-week intervention (5 hours/week; total: 80 hours) of either targeted spatial navigation or an active control group. The spatial navigation group engages in structured exploration of different cities using Google Street View that includes daily navigation challenges. The active control group watches and answers subjective questions about educational videos. Following a brief orientation, participants remotely self-administer the intervention on their home computer. In addition to feasibility and compliance measures, clinical and experimental cognitive measures as well as MRI scan data are collected pre-intervention and post-intervention to determine behavioural and neural efficacy.Ethics and disseminationEthics approval has been obtained from ethics boards at the University Health Network and University of Toronto. Findings will be presented at academic conferences and submitted to peer-reviewed journals.Trial registration numberVersion 3, ClinicalTrials.gov Registry (NCT04331392).

scholarly journals P88 Paroxysmal sympathetic storm and the role of beta-blockers in traumatic brain injury: a scoping review protocol

BJS Open ◽  
2021 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Stéphane Nguembu ◽  
Marco Meloni ◽  
Geneviève Endalle ◽  
Hugues Dokponou ◽  
Olaoluwa Ezekiel Dada ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Length Of Stay ◽  
Glasgow Coma Scale ◽  
Scoping Review ◽  
Beta Blockers ◽  
Clinical Signs ◽  
Sympathetic Hyperactivity ◽  
Paroxysmal Sympathetic Hyperactivity

Abstract Introduction Most cases of paroxysmal sympathetic hyperactivity (PSH) result from traumatic brain injury (TBI). Little is known about its pathophysiology and treatment, and several neuroprotective drugs are used including beta-blockers. The aim of our study is to collate existing evidence of the role of beta-blockers in the treatment of PSH. Method We will search MEDLINE, Web of Science, EMBASE, Cochrane, and Google Scholar. The search terms used will cover the following terms: “paroxysmal sympathetic hyperactivity”, “traumatic brain injury” and “beta-blockers.”: No language or geographical restrictions will be applied. Two independent co-authors will screen the titles and abstracts of each article following predefined inclusion and exclusion criteria. If there is a conflict the two reviewers will find a consensus and if they cannot a third co-author will decide. Using a pre-designed and pre-piloted data extraction form, data from each included citation will be collected (authors identification, study type, TBI severity, type of beta-blockers used, dosage of the drug, clinical signs of PSH, Glasgow Coma Scale, Glasgow Outcome Scale, mortality, morbidity and length of stay). Simple descriptive data analyses will be performed and the results will be presented both in a narrative and tabular form. Results The effectiveness of beta-blockers in post-TBI PHS will be evaluated through clinical signs of PHS(increased heart rate, respiratory rate, temperature, blood pressure, and sweating), Glasgow Coma Scale, and Glasgow Outcome Scale. mortality, morbidity and length of stay. Conclusion At the end of this scoping review we will design a systematic review with metaanalysis if there are a reasonable number of studies otherwise we will design a randomized controlled trial.

scholarly journals Age, Sex and Cerebral Microbleed Effects On White Matter Degradation After Traumatic Brain Injury

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 886-887
Author(s):  
Andrei Irimia ◽  
Ammar Dharani ◽  
Van Ngo ◽  
David Robles ◽  
Kenneth Rostowsky
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Diffusion Tensor ◽  
Diffuse Axonal Injury ◽  
Principal Component ◽  
Older Age ◽  
Analysis Of Covariance ◽  
Future Research ◽  
Cerebral Microbleed

Abstract Mild traumatic brain injury (mTBI) affects white matter (WM) integrity and accelerates neurodegeneration. This study assesses the effects of age, sex, and cerebral microbleed (CMB) load as predictors of WM integrity in 70 subjects aged 18-77 imaged acutely and ~6 months after mTBI using diffusion tensor imaging (DTI). Two-tensor unscented Kalman tractography was used to segment and cluster 73 WM structures and to map changes in their mean fractional anisotropy (FA), a surrogate measure of WM integrity. Dimensionality reduction of mean FA feature vectors was implemented using principal component (PC) analysis, and two prominent PCs were used as responses in a multivariate analysis of covariance. Acutely and chronically, older age was significantly associated with lower FA (F2,65 = 8.7, p &lt; .001, η2 = 0.2; F2,65 = 12.3, p &lt; .001, η2 = 0.3, respectively), notably in the corpus callosum and in dorsolateral temporal structures, confirming older adults’ WM vulnerability to mTBI. Chronically, sex was associated with mean FA (F2,65 = 5.0, p = 0.01, η2 = 0.1), indicating males’ greater susceptibility to WM degradation. Acutely, a significant association was observed between CMB load and mean FA (F2,65 = 5.1, p = 0.009, η2 = 0.1), suggesting that CMBs reflect the acute severity of diffuse axonal injury. Together, these findings indicate that older age, male sex, and CMB load are risk factors for WM degeneration. Future research should examine how sex- and age-mediated WM degradation lead to cognitive decline and connectome degeneration after mTBI.

scholarly journals Acoustofluidic separation enables early diagnosis of traumatic brain injury based on circulating exosomes

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zeyu Wang ◽  
Haichen Wang ◽  
Ryan Becker ◽  
Joseph Rufo ◽  
Shujie Yang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Flow Cytometry ◽  
Brain Injury ◽  
Early Diagnosis ◽  
Tissue Injury ◽  
Management Strategies ◽  
Acoustic Properties ◽  
Early Management ◽  
Biomarker Analysis ◽  
Downstream Analysis

AbstractTraumatic brain injury (TBI) is a global cause of morbidity and mortality. Initial management and risk stratification of patients with TBI is made difficult by the relative insensitivity of screening radiographic studies as well as by the absence of a widely available, noninvasive diagnostic biomarker. In particular, a blood-based biomarker assay could provide a quick and minimally invasive process to stratify risk and guide early management strategies in patients with mild TBI (mTBI). Analysis of circulating exosomes allows the potential for rapid and specific identification of tissue injury. By applying acoustofluidic exosome separation—which uses a combination of microfluidics and acoustics to separate bioparticles based on differences in size and acoustic properties—we successfully isolated exosomes from plasma samples obtained from mice after TBI. Acoustofluidic isolation eliminated interference from other blood components, making it possible to detect exosomal biomarkers for TBI via flow cytometry. Flow cytometry analysis indicated that exosomal biomarkers for TBI increase in the first 24 h following head trauma, indicating the potential of using circulating exosomes for the rapid diagnosis of TBI. Elevated levels of TBI biomarkers were only detected in the samples separated via acoustofluidics; no changes were observed in the analysis of the raw plasma sample. This finding demonstrated the necessity of sample purification prior to exosomal biomarker analysis. Since acoustofluidic exosome separation can easily be integrated with downstream analysis methods, it shows great potential for improving early diagnosis and treatment decisions associated with TBI.

Combined Memory Training: An Approach for Episodic Memory Deficits in Traumatic Brain Injury

2021 ◽  
Vol 30 (2S) ◽  
pp. 920-932
Author(s):  
Elisabeth Cochran D'Angelo ◽  
Beth A. Ober ◽  
Gregory K. Shenaut
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Treatment Group ◽  
Episodic Memory ◽  
Semantic Memory ◽  
Memory Deficits ◽  
Control Group ◽  
Wait List ◽  
Wait List Control Group ◽  
Wait List Control

Purpose The study aimed to test a combination of semantic memory and traditional episodic memory therapies on episodic memory deficits in adults with traumatic brain injury. Method Twenty-five participants who had been diagnosed with traumatic brain injury and had episodic memory deficits were randomly assigned either to a combined memory treatment group ( n = 16) or to a wait-list control group ( n = 9). Before and after treatment, they completed standardized neuropsychological testing for episodic memory and related cognitive domains, including the California Verbal Learning Test–Second Edition, the Controlled Oral Word Association Test, the University of Southern California Repeatable Episodic Memory Test, the Wechsler Abbreviated Scale of Intelligence–Second Edition Matrices, the Test of Everyday Attention, the Memory Assessment Clinics Self-Rating Scale, the Expressive Vocabulary Test–Second Edition, and the Story Recall subtest from the Rivermead Behavioural Memory Test. In addition to a traditional episodic memory therapy, the treatment group received a novel semantic memory–focused therapy, which involved participants finding meaningful connections between diverse concepts represented by sets of two or three words. Results The treatment group demonstrated statistically significant improvement in memory for list learning tasks, and there was a significant difference from pretest to posttest between the treatment group and the wait-list control group. Clinical significance was demonstrated for the treatment group using minimally important difference calculations. Conclusion Combined memory therapy resulted in significant improvements in episodic memory, semantic memory, and attention, in comparison to no treatment. Supplemental Material https://doi.org/10.23641/asha.14049968

scholarly journals Traumatic Brain Injury Caused by Motor Vehicle Collision and Alcoholism in Piauí

2016 ◽  
Vol 37 (03) ◽  
pp. 174-181
Author(s):  
Benjamim Vale ◽  
Juçara Castro ◽  
Marx Araújo ◽  
Herb Morais ◽  
Lívio Macêdo
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Motor Vehicle ◽  
Care Service ◽  
Diffuse Axonal Injury ◽  
Total Sample ◽  
Motor Vehicle Collision ◽  
Alcoholic Beverages ◽  
Trauma Patients ◽  
Vehicle Collision

Objectives To determine the relationship between alcohol consumption and the incidence of traumatic brain injury (TBI) with diffuse axonal injury (DAI), determining these indices, checking acquired comorbidities and characterizing the patients by gender, age and race/color, as well as describing the characteristics of the motor vehicle collision (vehicle, period of the day, day of the week and site) in people admitted to an emergency hospital in the city of Teresina, in the state of Piauí, Brazil. Methods We have analyzed the data contained in the medical records of patients admitted with a history of motor vehicle collision and severe TBI in intensive care units, based on the forms provided by the Mobile Emergency Care Service (SAMU, in the Portuguese acronym) in the period between February 28 and November 28, 2013. Results In the period covered by the present study, 200 individuals were analyzed, and 54 (27%) had consumed alcohol; of these 11 had DAI. Of the total sample, 17% (34) presented DAI, however, with unknown data regarding the consumption of alcoholic beverages. Conclusion Considering the data, we observed that the profile of the head trauma patients are brown men, mostly (53.5%) aged between 15 and 30 years. The collisions occurred mostly on weekends and at night (55%), and 89.5% of the crashes involved motorcycles.

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