Concentration of microtubule associated protein tau (MAPT) in urine and saliva as a potential biomarker of traumatic brain injury in relationship with blood–brain barrier disruption in postmortem examination

Olczak, Mieszko; Poniatowski, Łukasz A.; Niderla-Bielińska, Justyna; Kwiatkowska, Magdalena; Chutorański, Dominik; Tarka, Sylwia; Wierzba-Bobrowicz, Teresa

doi:10.1016/j.forsciint.2019.05.010

Cited by 24 publications

(20 citation statements)

References 77 publications

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“…There have been several recent clinical studies that have shown the potential role of biomarkers for the breakdown of the BBB in traumatic brain injury. The findings from a recent study showed that microtubule-associated protein tau (MAPT) in postmortem samples of saliva and urine was a potential biomarker for disruption of the BBB in traumatic brain injury [21]. A retrospective study of elderly patients with traumatic brain injury showed that in samples of extracellular fluid sampled by microdialysis, glutamate, glycerol, and fibroblast growth factor 2 (FGF2) were significantly increased [22].…”

Section: Discussionmentioning

confidence: 99%

Basic Fibroblast Growth Factor Reduces Permeability and Apoptosis of Human Brain Microvascular Endothelial Cells in Response to Oxygen and Glucose Deprivation Followed by Reoxygenation via the Fibroblast Growth Factor Receptor 1 (FGFR1)/ERK Pathway

Chen

Zhang

et al. 2019

Med Sci Monit

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The study was supported by the Foundation of the Program of Technology of Education Committee of Chongqing (No. KJQN201800122) and the Program of Technology of Science and Technology Committee of Yuzhong District in Chongqing (No. 20180131) Background: Disruption of the blood-brain barrier (BBB) is a mechanism in the pathogenesis of traumatic brain injury. Basic fibroblast growth factor (bFGF) is expressed in angiogenesis, neurogenesis, and neuronal survival. This study aimed to investigate the role of bFGF in vitro in human brain microvascular endothelial cells (HBMECs) challenged by oxygen-glucose deprivation/reperfusion (OGD/R). Material/Methods: HBMECs were cultured in glucose-free medium and an environment with <0.5% oxygen in an anaerobic chamber. Immunocytochemistry, Western blot, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to measure the protein and mRNA expression levels of bFGF, tight junction, adherens junction, apoptotic proteins, and matrix metalloproteinases (MMPs). The effects of bFGF on the viability of HBMECs was evaluated using the cell counting kit-8 (CCK-8) assay. Cell apoptosis was evaluated using the TUNEL assay, and endothelial permeability was quantified using a transwell migration assay with fluorescein isothiocyanate (FITC) conjugated with dextran. The effects of bFGF were evaluated following inhibition of fibroblast growth factor receptor 1 (FGFR1) with PD173074 and inhibition of ERK with PD98059. Results: Following OGD/R of HBMECs, bFGF significantly reduced cell permeability and apoptosis and significantly inhibited the down-regulation of the expressions of proteins associated with tight junctions, adherens junctions, apoptosis and matrix metalloproteinases (MMPs). The effects of bFGF were mediated by the activation of FGFR1 and ERK, as they were blocked by FGFR1 and ERK inhibitors. Conclusions: Permeability and apoptosis of HBMECs challenged by OGD/R were reduced by bFGF by activation of the FGFR1 and the ERK pathway.

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Section: Discussionmentioning

confidence: 99%

Basic Fibroblast Growth Factor Reduces Permeability and Apoptosis of Human Brain Microvascular Endothelial Cells in Response to Oxygen and Glucose Deprivation Followed by Reoxygenation via the Fibroblast Growth Factor Receptor 1 (FGFR1)/ERK Pathway

Chen

Zhang

et al. 2019

Med Sci Monit

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“…Analytic issues such as test-retest reliability, test sensitivity, inconsistencies across test platforms, and issues related to storage and handling of samples have not been addressed in this work (for a discussion of some of these issues see [13]. We focused on blood levels of biomarkers and did not address biomarker levels in the cerebrospinal fluid, urine, or saliva [130,131]. Evidence from the clinical setting and from animal models indicates a disruption of the blood brain barrier occurs after moderate to severe traumatic brain injury [132][133][134][135][136][136][137][138][139] and that biomarkers can cross the blood brain barrier into the blood [11,62].…”

Section: Discussionmentioning

confidence: 99%

Blood biomarkers for mild traumatic brain injury: a selective review of unresolved issues

et al. 2021

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Background The use of blood biomarkers after mild traumatic brain injury (mTBI) has been widely studied. We have identified eight unresolved issues related to the use of five commonly investigated blood biomarkers: neurofilament light chain, ubiquitin carboxy-terminal hydrolase-L1, tau, S100B, and glial acidic fibrillary protein. We conducted a focused literature review of unresolved issues in three areas: mode of entry into and exit from the blood, kinetics of blood biomarkers in the blood, and predictive capacity of the blood biomarkers after mTBI. Findings Although a disruption of the blood brain barrier has been demonstrated in mild and severe traumatic brain injury, biomarkers can enter the blood through pathways that do not require a breach in this barrier. A definitive accounting for the pathways that biomarkers follow from the brain to the blood after mTBI has not been performed. Although preliminary investigations of blood biomarkers kinetics after TBI are available, our current knowledge is incomplete and definitive studies are needed. Optimal sampling times for biomarkers after mTBI have not been established. Kinetic models of blood biomarkers can be informative, but more precise estimates of kinetic parameters are needed. Confounding factors for blood biomarker levels have been identified, but corrections for these factors are not routinely made. Little evidence has emerged to date to suggest that blood biomarker levels correlate with clinical measures of mTBI severity. The significance of elevated biomarker levels thirty or more days following mTBI is uncertain. Blood biomarkers have shown a modest but not definitive ability to distinguish concussed from non-concussed subjects, to detect sub-concussive hits to the head, and to predict recovery from mTBI. Blood biomarkers have performed best at distinguishing CT scan positive from CT scan negative subjects after mTBI.

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“…There is a study on mice in the literature [74]. There are also studies on urine and saliva samples [75]. These studies are important for understanding brain functions and diseases.…”

Section: Discussionmentioning

confidence: 99%

Investigation of polymorphic variants of SLC6A4, TPH-1, and TPH-2 genes in cases of completed suicide

Kilicaslan,

Cumaogullari,

Emiral

et al. 2022

J. Mens. Health

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Background and objective: Serotonin plays an important role in the pathophysiology of aggressive behavior. Low serotonin levels and altered functions of serotonin receptors affect suicidal behavior.TPH-1, TPH-2 and SLC6A4 genes have important roles in serotonin production and degradation pathways. In this study, polymorphic variants of the TPH-1, TPH-2 and SLC6A4 genes, rs1800532, rs7305115, rs6355 and rs1386494, were investigated in 100 completed suicides and 100 healthy individuals. Materials and methods:After DNA isolation, a new polymerase chain reaction technology KASP TM (Competitive allele-specific polymerase chain reaction method), was used in the genotyping of the selected gene variants.Results: No statistically significant difference was found for the genotype and individual allele frequencies of the polymorphic variants between suicide and control groups, as well as between men and women in suicide cases. However, we observed non-significant tendencies of increased minor alleles in suicidal men for all TPH SNPs. Conclusions:More molecular genetic research studies are needed to understand the pathophysiology of suicide and to reveal its relationship with gender.

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Concentration of microtubule associated protein tau (MAPT) in urine and saliva as a potential biomarker of traumatic brain injury in relationship with blood–brain barrier disruption in postmortem examination

Cited by 24 publications

References 77 publications

Basic Fibroblast Growth Factor Reduces Permeability and Apoptosis of Human Brain Microvascular Endothelial Cells in Response to Oxygen and Glucose Deprivation Followed by Reoxygenation via the Fibroblast Growth Factor Receptor 1 (FGFR1)/ERK Pathway

Basic Fibroblast Growth Factor Reduces Permeability and Apoptosis of Human Brain Microvascular Endothelial Cells in Response to Oxygen and Glucose Deprivation Followed by Reoxygenation via the Fibroblast Growth Factor Receptor 1 (FGFR1)/ERK Pathway

Blood biomarkers for mild traumatic brain injury: a selective review of unresolved issues

Investigation of polymorphic variants of SLC6A4, TPH-1, and TPH-2 genes in cases of completed suicide

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