scholarly journals Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury

2021 ◽  
Vol 22 (4) ◽  
pp. 1563
Author(s):  
Shalini Das Gupta ◽  
Robert Ciszek ◽  
Mette Heiskanen ◽  
Niina Lapinlampi ◽  
Janne Kukkonen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Small Rna Sequencing ◽  
Sprague Dawley ◽  
Diagnostic Biomarkers ◽  
Fluid Percussion Injury ◽  
Diagnostic Potential ◽  
Droplet Pcr ◽  
And Control

Noninvasive, affordable circulating biomarkers for difficult-to-diagnose mild traumatic brain injury (mTBI) are an unmet medical need. Although blood microRNA (miRNA) levels are reportedly altered after traumatic brain injury (TBI), their diagnostic potential for mTBI remains inconclusive. We hypothesized that acutely altered plasma miRNAs could serve as diagnostic biomarkers both in the lateral fluid percussion injury (FPI) model and clinical mTBI. We performed plasma small RNA-sequencing from adult male Sprague–Dawley rats (n = 31) at 2 days post-TBI, followed by polymerase chain reaction (PCR)-based validation of selected candidates. miR-9a-3p, miR-136-3p, and miR-434-3p were identified as the most promising candidates at 2 days after lateral FPI. Digital droplet PCR (ddPCR) revealed 4.2-, 2.8-, and 4.6-fold elevations in miR-9a-3p, miR-136-3p, and miR-434-3p levels (p < 0.01 for all), respectively, distinguishing rats with mTBI from naïve rats with 100% sensitivity and specificity. DdPCR further identified a subpopulation of mTBI patients with plasma miR-9-3p (n = 7/15) and miR-136-3p (n = 5/15) levels higher than one standard deviation above the control mean at <2 days postinjury. In sTBI patients, plasma miR-9-3p levels were 6.5- and 9.2-fold in comparison to the mTBI and control groups, respectively. Thus, plasma miR-9-3p and miR-136-3p were identified as promising biomarker candidates for mTBI requiring further evaluation in a larger patient population.

scholarly journals Electrophysiological Markers of Visuospatial Attention Recovery after Mild Traumatic Brain Injury

2019 ◽  
Vol 9 (12) ◽  
pp. 343 ◽  
Author(s):  
Julie Bolduc-Teasdale ◽  
Pierre Jolicoeur ◽  
Michelle McKerral
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Short Term Memory ◽  
Information Processing Speed ◽  
Visual Short Term Memory ◽  
Trail Making ◽  
Postconcussion Symptoms ◽  
Map Search ◽  
And Control

Objective: Attentional problems are amongst the most commonly reported complaints following mild traumatic brain injury (mTBI), including difficulties orienting and disengaging attention, sustaining it over time, and dividing attentional resources across multiple simultaneous demands. The objective of this study was to track, using a single novel electrophysiological task, various components associated with the deployment of visuospatial selective attention. Methods: A paradigm was designed to evoke earlier visual evoked potentials (VEPs), as well as attention-related and visuocognitive ERPs. Data from 36 individuals with mTBI (19 subacute, 17 chronic) and 22 uninjured controls are presented. Postconcussion symptoms (PCS), anxiety (BAI), depression (BDI-II) and visual attention (TEA Map Search, DKEFS Trail Making Test) were also assessed. Results: Earlier VEPs (P1, N1), as well as processes related to visuospatial orientation (N2pc) and encoding in visual short-term memory (SPCN), appear comparable in mTBI and control participants. However, there appears to be a disruption in the spatiotemporal dynamics of attention (N2pc-Ptc, P2) in subacute mTBI, which recovers within six months. This is also reflected in altered neuropsychological performance (information processing speed, attentional shifting). Furthermore, orientation of attention (P3a) and working memory processes (P3b) are also affected and remain as such in the chronic post-mTBI period, in co-occurrence with persisting postconcussion symptomatology. Conclusions: This study adds original findings indicating that such a sensitive and rigorous ERP task implemented at diagnostic and follow-up levels could allow for the identification of subtle but complex brain activation and connectivity deficits that can occur following mTBI.

scholarly journals Repeated Mild Traumatic Brain Injury Results in Long-Term White-Matter Disruption

2014 ◽  
Vol 34 (4) ◽  
pp. 715-723 ◽  
Author(s):  
Virginia Donovan ◽  
Claudia Kim ◽  
Ariana K Anugerah ◽  
Jacqueline S Coats ◽  
Udochuwku Oyoyo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Mild Traumatic Brain Injury ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Health Concern ◽  
Sprague Dawley ◽  
G Ratio

Mild traumatic brain injury (mTBI) is an increasing public health concern as repetitive injuries can exacerbate existing neuropathology and result in increased neurologic deficits. In contrast to other models of repeated mTBI (rmTBI), our study focused on long-term white-matter abnormalities after bilateral mTBIs induced 7 days apart. A controlled cortical impact (CCI) was used to induce an initial mTBI to the right cortex of Single and rmTBI Sprague Dawley rats, followed by a second injury to the left cortex of rmTBI animals. Shams received only a craniectomy. Ex vivo diffusion tensor imaging (DTI), transmission electron microscopy (TEM), and histology were performed on the anterior corpus callosum at 60 days after injury. The rmTBI animals showed a significant bilateral increase in radial diffusivity (myelin), while only modest changes in axial diffusivity (axonal) were seen between the groups. Further, the rmTBI group showed an increased g-ratio and axon caliber in addition to myelin sheath abnormalities using TEM. Our DTI results indicate ongoing myelin changes, while the TEM data show continuing axonal changes at 60 days after rmTBI. These data suggest that bilateral rmTBI induced 7 days apart leads to progressive alterations in white matter that are not observed after a single mTBI.

scholarly journals Examining the Progressive Behavior and Neuropathological Outcomes Associated with Chronic Repetitive Mild Traumatic Brain Injury in Rats

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Eric Eyolfson ◽  
Glenn R Yamakawa ◽  
Yannick Griep ◽  
Reid Collins ◽  
Thomas Carr ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Motor Behavior ◽  
Functional Change ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Behavioral Impairment ◽  
Motor Disturbance ◽  
Ventricle Size

Abstract While the physical and behavioral symptomologies associated with a single mild traumatic brain injury (mTBI) are typically transient, repetitive mTBIs (RmTBI) have been associated with persisting neurological deficits. Therefore, this study examined the progressive changes in behavior and the neuropathological outcomes associated with chronic RmTBI through adolescence and adulthood in male and female Sprague Dawley rats. Rats experienced 2 mTBIs/week for 15 weeks and were periodically tested for changes in motor behavior, cognitive function, emotional disturbances, and aggression. Brain tissue was examined for neuropathological changes in ventricle size and presentation of Iba1 and GFAP. We did not see progressively worse behavioral impairments with the accumulation of injuries or time, but did find evidence for neurological and functional change (motor disturbance, reduced exploration, reduced aggression, alteration in depressive-like behavior, deficits in short-term working memory). Neuropathological assessment of RmTBI animals identified an increase in ventricle size, prolonged changes in GFAP, and sex differences in Iba1, in the corpus callosum, thalamus, and medial prefrontal cortex. Telomere length reduced exponentially as the injury load increased. Overall, chronic RmTBI did not result in accumulating behavioral impairment, and there is a need to further investigate progressive behavioral changes associated with repeated injuries in adolescence and young adulthood.

Respiratory Sinus Arrhythmia Correlates With Depressive Symptoms Following Mild Traumatic Brain Injury

2020 ◽  
pp. 1-13
Author(s):  
Emma Brandt ◽  
J. Kevin Wilson ◽  
Rebecca E. Rieger ◽  
Darbi Gill ◽  
Andrew R. Mayer ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Depressive Symptoms ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Respiratory Sinus Arrhythmia ◽  
Clinical Population ◽  
Post Injury ◽  
Sinus Arrhythmia ◽  
And Control ◽  
Depressive Episodes

Abstract. Depression is a pervasive psychiatric problem following mild traumatic brain injury (mTBI). However, the onset and course of symptom expression following mTBI can differ from that of spontaneous episodes of depression. Here, we aimed to assess a physiological metric closely linked to depression: respiratory sinus arrhythmia (RSA), a measure of high frequency heart rate variability. RSA is reduced during depressive episodes, and higher resting RSA has been shown to predict future recovery from depression. In this study, we investigated if these patterns were observed throughout the typical timeframe of sub-acute mTBI recovery. Although RSA did not differ between mTBI ( n = 50) and control ( n = 27) groups, depressive symptoms were reliably correlated with RSA only in the mTBI group. This pattern was consistent 2 weeks, 2 months, and 4 months post-injury. Furthermore, resting RSA shortly following injury predicted the trajectory of depressive symptoms 2 months later. These findings generalize the connection between RSA and depression to a clinical population where depressive symptoms are common but often difficult to parse from other post-trauma consequences.

scholarly journals Dynamics of clusterin protein expression in the brain and plasma following experimental traumatic brain injury

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shalini Das Gupta ◽  
Anssi Lipponen ◽  
Kaisa M. A. Paldanius ◽  
Noora Puhakka ◽  
Asla Pitkänen
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein Expression ◽  
Fold Increase ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Post Injury ◽  
Fluid Percussion Injury ◽  
Clusterin Protein ◽  
The Brain

AbstractProgress in the preclinical and clinical development of neuroprotective and antiepileptogenic treatments for traumatic brain injury (TBI) necessitates the discovery of prognostic biomarkers for post-injury outcome. Our previous mRNA-seq data revealed a 1.8–2.5 fold increase in clusterin mRNA expression in lesioned brain areas in rats with lateral fluid-percussion injury (FPI)-induced TBI. On this basis, we hypothesized that TBI leads to increases in the brain levels of clusterin protein, and consequently, increased plasma clusterin levels. For evaluation, we induced TBI in adult male Sprague-Dawley rats (n = 80) by lateral FPI. We validated our mRNA-seq findings with RT-qPCR, confirming increased clusterin mRNA levels in the perilesional cortex (FC 3.3, p < 0.01) and ipsilateral thalamus (FC 2.4, p < 0.05) at 3 months post-TBI. Immunohistochemistry revealed a marked increase in extracellular clusterin protein expression in the perilesional cortex and ipsilateral hippocampus (7d to 1 month post-TBI), and ipsilateral thalamus (14d to 12 months post-TBI). In the thalamus, punctate immunoreactivity was most intense around activated microglia and mitochondria. Enzyme-linked immunoassays indicated that an acute 15% reduction, rather than an increase in plasma clusterin levels differentiated animals with TBI from sham-operated controls (AUC 0.851, p < 0.05). Our findings suggest that plasma clusterin is a candidate biomarker for acute TBI diagnosis.

scholarly journals A simple rat model of mild traumatic brain injury: device to reproduce anatomical and neurological changes of mild traumatic brain injury

2016 ◽  
Author(s):  
Ho Jeong Kim ◽  
Soo Jeong Han
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Water Pressure ◽  
Brain Mri ◽  
Free Fall ◽  
Absolute Number ◽  
Grid Floor ◽  
Sprague Dawley ◽  
The Brain

Mild traumatic brain injury typically involves temporary impairment of neurological function. Previous studies used the water pressure or rotational injury for designing the device to make a rat mild traumatic brain injury model. The objective of this study was to make a simple model of mild traumatic brain injury in rat. The device consisted of a free-fall impactor that was targeted onto the rat skull. The weight (175g) was freely dropped 30cm to rat’s skull bregma. We installed a safety device made of acrylic panel. To confirm a mild traumatic brain injury in 36 Sprague–Dawley rats, we performed the brain magnetic resonance image(MRI) within 24 hours after injury. We evaluated behavior and chemical changes in rats before and after mild traumatic brain injury. The brain MRI did not show high or low signal intensity in 34 rats. The mobility on grid floor was decreased after mild traumatic brain injury. Absolute number of foot-fault and foot-fault ratio were decreased after mild traumatic brain. But the difference of ratio was lesser than absolute number of foot-fault. These results show that the device is capable of reproducing mild traumatic brain injury in rat. Our device can reduce the potential to cause brain hemorrhage and reflect the mechanism of real mild traumatic brain injury compared with existing methods and behaviors. This model can be useful in exploring physiology and management of mild traumatic brain injury.

scholarly journals A simple rat model of mild traumatic brain injury: a device to reproduce anatomical and neurological changes of mild traumatic brain injury

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2818 ◽  
Author(s):  
Ho Jeong Kim ◽  
Soo Jeong Han
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Water Pressure ◽  
Brain Mri ◽  
Free Fall ◽  
Absolute Number ◽  
Grid Floor ◽  
Sprague Dawley ◽  
The Brain

Mild traumatic brain injury typically involves temporary impairment of neurological function. Previous studies used water pressure or rotational injury for designing the device to make a rat a mild traumatic brain injury model. The objective of this study was to make a simple model of causing mild traumatic brain injury in rats. The device consisted of a free-fall impactor that was targeted onto the rat skull. The weight (175 g) was freely dropped 30 cm to rat’s skull bregma. We installed a safety device made of acrylic panel. To confirm a mild traumatic brain injury in 36 Sprague-Dawley rats, we performed magnetic resonance imaging (MRI) of the brain within 24 h after injury. We evaluated behavior and chemical changes in rats before and after mild traumatic brain injury. The brain MRI did not show high or low signal intensity in 34 rats. The mobility on grid floor was decreased after mild traumatic brain injury. The absolute number of foot-fault and foot-fault ratio were decreased after mild traumatic brain injury. However, the difference of the ratio was a less than absolute number of foot-fault. These results show that the device is capable of reproducing mild traumatic brain injury in rats. Our device can reduce the potential to cause brain hemorrhage and reflect the mechanism of real mild traumatic brain injury compared with existing methods and behaviors. This model can be useful in exploring physiology and management of mild traumatic brain injury.

scholarly journals A simple rat model of mild traumatic brain injury: device to reproduce anatomical and neurological changes of mild traumatic brain injury

2016 ◽  
Author(s):  
Ho Jeong Kim ◽  
Soo Jeong Han
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Water Pressure ◽  
Brain Mri ◽  
Free Fall ◽  
Absolute Number ◽  
Grid Floor ◽  
Sprague Dawley ◽  
The Brain

Mild traumatic brain injury typically involves temporary impairment of neurological function. Previous studies used the water pressure or rotational injury for designing the device to make a rat mild traumatic brain injury model. The objective of this study was to make a simple model of mild traumatic brain injury in rat. The device consisted of a free-fall impactor that was targeted onto the rat skull. The weight (175g) was freely dropped 30cm to rat’s skull bregma. We installed a safety device made of acrylic panel. To confirm a mild traumatic brain injury in 36 Sprague–Dawley rats, we performed the brain magnetic resonance image(MRI) within 24 hours after injury. We evaluated behavior and chemical changes in rats before and after mild traumatic brain injury. The brain MRI did not show high or low signal intensity in 34 rats. The mobility on grid floor was decreased after mild traumatic brain injury. Absolute number of foot-fault and foot-fault ratio were decreased after mild traumatic brain. But the difference of ratio was lesser than absolute number of foot-fault. These results show that the device is capable of reproducing mild traumatic brain injury in rat. Our device can reduce the potential to cause brain hemorrhage and reflect the mechanism of real mild traumatic brain injury compared with existing methods and behaviors. This model can be useful in exploring physiology and management of mild traumatic brain injury.

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