Alteration in BDNF and its receptors, full-length and truncated TrkB and p75NTR following penetrating traumatic brain injury

Rostami, Elham; Krueger, Frank; Plantman, Stefan; Davidsson, Johan; Agoston, Denes V.; Grafman, Jordan; Risling, Mårten

doi:10.1016/j.brainres.2013.10.047

Cited by 67 publications

(61 citation statements)

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Section: Preclinicalmentioning

confidence: 99%

“…This is probably one of the most detailed follow-up neurotrauma studies that has ever been conducted. This material has been employed to reveal the importance of the growth factor BDNF on the outcome of the injury an observation that later was brought back for further investigation in a suitable animal model (Rostami et al, 2014).In summary, blast TBI involves complex energy transfer and several possible mechanisms. The primary blast wave, acceleration generated tissue strain, smoke and heat can induce both mild TBI and more severe injuries.…”

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confidence: 99%

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The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

Huang

Risling

Baker

2016

Psychoneuroendocrinology

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SummaryBackground: Pervasive use of improvised explosive devices (IEDs), rocket-propelled grenades, and land mines in the recent conflicts in Iraq and Afghanistan has brought traumatic brain injury (TBI) and its impact on health outcomes into public awareness. Blast injuries have been deemed signature wounds of these wars. War-related TBI is not new, having become prevalent during WWI and remaining medically relevant in WWII and beyond. Medicine's past attempts to accurately diagnose and disentangle the pathophysiology of war-related TBI parallels current lines of inquiry and highlights limitations in methodology and attribution of symptom etiology, be it organic, psychological, or behavioral. New approaches and biomarkers are needed. Preclinical: Serological biomarkers and biomarkers of injury obtained with imaging techniques represent cornerstones in the translation between experimental data and clinical observations. Experimental models for blast related TBI and PTSD can generate critical data on injury threshold, for example for white matter injury from acceleration. Carefully verified and validated models can be evaluated with gene expression arrays and proteomics to identify new candidates for serological biomarkers. Such models can also be analyzed with diffusion MRI and microscopy in order to identify criteria for detection of diffuse white matter injuries, such as DAI (diffuse axonal injury). The experimental models can also be analyzed with focus on injury outcome in brain stem regions, such as locus coeruleus or nucleus raphe magnus that can be involved in response to anxiety changes. * Corresponding author at: UCSD Radiology Imaging Laboratory, San Diego, CA 92121, USA. Tel.: +1 858 534 1254; fax: +1 8585346046. E-mail address: mxhuang@ucsd.edu (M. Huang). Clinical: Mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. There is accumulating evidence that injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1-4 Hz) that can be measured and localized by magnetoencephalography (MEG). MEG imaging detects TBI abnormalities at the rates of 87% for the mild TBI, group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities are 96% and 77% for the blast and non-blast TBI groups, respectively. There is emerging evidence based on fMRI and MEG studies showing hyper-activity in the amygdala and hypo-activity in prefrontal cortex in individuals with PTSD. MEG signal may serve as a sensitive imaging marker for mTBI, distinguishable from abnormalities generated in association with PTSD. More work is needed to fully describe physiological mechanisms of post-concussive symptoms.Published by Elsevier Ltd. BackgroundBlast injuries are deemed the signature wounds of the first wars (Afghanistan and Iraq) of the 21st century (Lancet, 2007;Galarneau et al., 2008). According to a recent U.S. Department Veterans Affairs (DVA) ...

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Section: Preclinicalmentioning

confidence: 99%

mentioning

confidence: 99%

The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

Huang

Risling

Baker

2016

Psychoneuroendocrinology

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“…TBI survivors, commonly suffer persisting cognitive dysfunction, and have a heightened risk of premature death, progressive neurodegeneration, and Alzheimer's disease 2, 3. The pathophysiological mechanisms governing short‐ and long‐term TBI outcomes include axonal injury3, blood‐brain barrier disruption4, glutamate neurotoxicity5, neuroenergetic deficits6, and lack of neurotrophic support 7. These neurochemical signatures also provide an opportunity for identifying molecules in body fluids that may serve as candidate biomarkers with putative clinical relevance 8, 9…”

Section: Introductionmentioning

confidence: 99%

Elevated glutamate and lactate predict brain death after severe head trauma

Stefani

Modkovski

Hansel

et al. 2017

Ann Clin Transl Neurol

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ObjectiveClinical neurological assessment is challenging for severe traumatic brain injury (TBI) patients in the acute setting. Waves of neurochemical abnormalities that follow TBI may serve as fluid biomarkers of neurological status. We assessed the cerebrospinal fluid (CSF) levels of glutamate, lactate, BDNF, and GDNF, to identify potential prognostic biomarkers of neurological outcome.MethodsThis cross‐sectional study was carried out in a total of 20 consecutive patients (mean [SD] age, 29 [13] years; M/F, 9:1) with severe TBI Glasgow Coma Scale ≤ 8 and abnormal computed tomography scan on admission. Patients were submitted to ventricular drainage and had CSF collected between 2 and 4 h after hospital admission. Patients were then stratified according to two clinical outcomes: deterioration to brain death (nonsurvival, n = 6) or survival (survival, n = 14), within 3 days after hospital admission. CSF levels of brain‐derived substances were compared between nonsurvival and survival groups. Clinical and neurological parameters were also assessed.ResultsGlutamate and lactate are significantly increased in nonsurvival relative to survival patients. We tested the accuracy of both biomarkers to discriminate patient outcome. Setting a cutoff of >57.75, glutamate provides 80.0% of sensitivity and 84.62% of specificity (AUC: 0.8214, 95% CL: 54.55–98.08%; and a cutoff of >4.65, lactate has 100% of sensitivity and 85.71% of specificity (AUC: 0.8810, 95% CL: 54.55–98.08%). BDNF and GDNF did not discriminate poor outcome.InterpretationThis early study suggests that glutamate and lactate concentrations at hospital admission accurately predict death within 3 days after severe TBI.

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“…This material has been used to analyze the relation between the TBI and PTSD 77 or other disorders. A new model for experimental penetrating TBI has been used to analyze changes in brain-derived neurotrophic factor (BDNF) and neurotrophin receptors, 78 since it was shown that BDNF polymorphism has a strong effect on outcome in the Vietnam head injury study. 79 Thus, an analysis of catecholamines and serotonin in penetrating TBI could be of interest.…”

Section: Tbi and Monoamine Turnovermentioning

confidence: 99%

Neurotransmitter Systems in a Mild Blast Traumatic Brain Injury Model: Catecholamines and Serotonin

Kawa

Arborelius

Yoshitake

et al. 2015

Journal of Neurotrauma

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Exposure to improvised explosive devices can result in a unique form of traumatic brain injury-blast-induced traumatic brain injury (bTBI). At the mild end of the spectrum (mild bTBI [mbTBI]), there are cognitive and mood disturbances. Similar symptoms have been observed in post-traumatic stress disorder caused by exposure to extreme psychological stress without physical injury. A role of the monoaminergic system in mood regulation and stress is well established but its involvement in mbTBI is not well understood. To address this gap, we used a rodent model of mbTBI and detected a decrease in immobility behavior in the forced swim test at 1 d post-exposure, coupled with an increase in climbing behavior, but not after 14 d or later, possibly indicating a transient increase in anxiety-like behavior. Using in situ hybridization, we found elevated messenger ribonucleic acid levels of both tyrosine hydroxylase and tryptophan hydroxylase 2 in the locus coeruleus and the dorsal raphe nucleus, respectively, as early as 2 h post-exposure. High-performance liquid chromatography analysis 1 d post-exposure primarily showed elevated noradrenaline levels in several forebrain regions. Taken together, we report that exposure to mild blast results in transient changes in both anxiety-like behavior and brain region-specific molecular changes, implicating the monoaminergic system in the pathobiology of mbTBI.

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Alteration in BDNF and its receptors, full-length and truncated TrkB and p75NTR following penetrating traumatic brain injury

Cited by 67 publications

References 61 publications

The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

Elevated glutamate and lactate predict brain death after severe head trauma

Neurotransmitter Systems in a Mild Blast Traumatic Brain Injury Model: Catecholamines and Serotonin

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