scholarly journals Strain and rate-dependent neuronal injury in a 3D in vitro compression model of traumatic brain injury

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Eyal Bar-Kochba ◽  
Mark T. Scimone ◽  
Jonathan B. Estrada ◽  
Christian Franck
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Injury ◽  
Rate Dependent ◽  
Compression Model

scholarly journals Neuroinflammation Mediated by Glia Maturation Factor Exacerbates Neuronal Injury in an in vitro Model of Traumatic Brain Injury

2020 ◽  
Vol 37 (14) ◽  
pp. 1645-1655 ◽  
Author(s):  
Mohammad Ejaz Ahmed ◽  
Govindhasamy Pushpavathi Selvakumar ◽  
Duraisamy Kempuraj ◽  
Sudhanshu P. Raikwar ◽  
Ramasamy Thangavel ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
In Vitro Model ◽  
Neuronal Injury ◽  
Glia Maturation Factor ◽  
Maturation Factor ◽  
Vitro Model

scholarly journals Controlled Decompression Attenuates Compressive Injury following Traumatic Brain Injury via TREK-1-Mediated Inhibition of Necroptosis and Neuroinflammation

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Tao Chen ◽  
Xiao Qian ◽  
Jie Zhu ◽  
Li-Kun Yang ◽  
Yu-Hai Wang
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Hypertension ◽  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Neuronal Injury ◽  
K Channel ◽  
Protective Effects

Decompressive craniectomy is an effective strategy to reduce intracranial hypertension after traumatic brain injury (TBI), but it is related to many postoperative complications, such as delayed intracranial hematoma and diffuse brain swelling. Our previous studies have demonstrated that controlled decompression (CDC) surgery attenuates brain injury and reduces the rate of complications after TBI. Here, we investigated the potential molecular mechanisms of CDC in experimental models. The in vitro experiments were performed in a traumatic neuronal injury (TNI) model following compression treatment in primary cultured cortical neurons. We found that compression aggravates TNI-induced neuronal injury, which was significantly attenuated by CDC for 2 h or 3 h. The results of immunocytochemistry showed that CDC reduced neuronal necroptosis and activation of RIP3 induced by TNI and compression, with no effect on RIP1 activity. These protective effects were associated with decreased levels of inflammatory cytokines and preserved intracellular Ca2+ homeostasis. In addition, the expression of the two-pore domain K+ channel TREK-1 and its activity was increased by compression and prolonged by CDC. Treatment with the TREK-1 blockers, spadin or SID1900, could partially prevent the effects of CDC on intracellular Ca2+ metabolism, necroptosis, and neuronal injury following TNI and compression. Using a traumatic intracranial hypertension model in rats, we found that CDC for 20 min or 30 min was effective in alleviating brain edema and locomotor impairment in vivo. CDC significantly inhibited neuronal necroptosis and neuroinflammation and increased TREK-1 activation, and the CDC-induced protection in vivo was attenuated by spadin and SID1900. In summary, CDC is effective in alleviating compressive neuronal injury both in vitro and in vivo, which is associated with the TREK-1-mediated attenuation of intracellular Ca2+ overload, neuronal necroptosis, and neuroinflammation.

Abstract P747: Gpr68 Play a Protective Role in Ischemic Stroke in Mice

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
tao wang ◽  
Guokun Zhou ◽  
mingdi he ◽  
yuanyuan xu ◽  
w.g. Rusyniak ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Neuronal Injury ◽  
Protective Role ◽  
Functional Screening ◽  
Rt Pcr ◽  
Brain Neurons ◽  
Acid Sensing Ion Channels ◽  
The Brain

Introduction: Acidosis is one prevalent phenomenon in ischemic stroke. The literature has shown that protons directly gate acid-sensing ion channels (ASICs) and proton-activated chloride channel, both lead to neuronal injury However, it is unclear whether protons activate metabotropic pathways in brain neurons. There are four proton-sensitive G-protein coupled receptors (GPCRs): GPR4, GPR65, GPR68 and GPR132. It remains unknown whether any of these GPCRs mediate acid-induced signals in brain neurons or whether they contribute to ischemia-induced brain injury. Methods: Total RNA from human cortical tissue or mouse brain was isolated using TRIzol and an RNase Kit. Standard RT-PCR was performed to determine the expression of these GPCRs in the brain. An in vitro slice injury model was used for functional screening. To determine the effect of ischemia, WT and knockout male mice were subjected to MCAO. To study brain injury, brains were sectioned coronally at 1 mm intervals and stained by vital dye immersion: (2%) 2,3,5-triphenyltetrazolium hydrochloride (TTC). Locomotor analysis and corner test were used to assess behavior outcome. Adeno-associated virus (AAV) -mediated gene delivery was used to determine the outcome of GPR68 overexpression. Results: RT-PCR showed that brain tissue expressed GPR4, -65, and -68. The expression of GPR68 was evident at 30 cycles. In organotypic slices, compared to the WT, deleting GPR4 or GPR65 had no effect while deleting GPR68 significantly increased acidosis-induced neuronal injury. At both 24 hour and 72 hour after 45 minutes MCAO, GPR68 deletion increased brain injury (p=0.0020 for 24hour, p=0.0392 for 72hour, Mann-Whitney U test). WT and GPR68-/- mice did not differ in baseline locomotor activities or corner test. On the third day following MCAO, GPR68-/- exhibited significantly more left rotations (p=0.0287, Mann-Whitney U test) than WT animals. Lastly, mice receiving AAV-GPR68 exhibited an average infarct of 21.97 ± 12.4%, significantly (p = 0.0022, Mann-Whitney U test) smaller than those receiving AAV-GFP (37.2 ± 6.8%). Conclusion: These data showed that GPR68 functions as a neuroprotective proton receptor in the brain.

scholarly journals Hydrogen exerts neuroprotection by activation of the miR‐21/PI3K/AKT/GSK‐3β pathway in an in vitro model of traumatic brain injury

2020 ◽  
Vol 24 (7) ◽  
pp. 4061-4071 ◽  
Author(s):  
Lu Wang ◽  
Zhenyu Yin ◽  
Feng Wang ◽  
Zhaoli Han ◽  
Yifeng Wang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
In Vitro Model ◽  
Vitro Model ◽  
Gsk 3Β

scholarly journals Traumatic brain injury in mice induces changes in the expression of the XCL1/XCR1 and XCL1/ITGA9 axes

2020 ◽  
Vol 72 (6) ◽  
pp. 1579-1592
Author(s):  
Agata Ciechanowska ◽  
Katarzyna Popiolek-Barczyk ◽  
Katarzyna Ciapała ◽  
Katarzyna Pawlik ◽  
Marco Oggioni ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Therapeutic Potential ◽  
Brain Structures ◽  
Pharmacological Intervention ◽  
Brain Areas ◽  
Cellular Origin ◽  
Protein Levels ◽  
Chemokine Ligand

Abstract Background Every year, millions of people suffer from various forms of traumatic brain injury (TBI), and new approaches with therapeutic potential are required. Although chemokines are known to be involved in brain injury, the importance of X-C motif chemokine ligand 1 (XCL1) and its receptors, X-C motif chemokine receptor 1 (XCR1) and alpha-9 integrin (ITGA9), in the progression of TBI remain unknown. Methods Using RT-qPCR/Western blot/ELISA techniques, changes in the mRNA/protein levels of XCL1 and its two receptors, in brain areas at different time points were measured in a mouse model of TBI. Moreover, their cellular origin and possible changes in expression were evaluated in primary glial cell cultures. Results Studies revealed the spatiotemporal upregulation of the mRNA expression of XCL1, XCR1 and ITGA9 in all the examined brain areas (cortex, thalamus, and hippocampus) and at most of the evaluated stages after brain injury (24 h; 4, 7 days; 2, 5 weeks), except for ITGA9 in the thalamus. Moreover, changes in XCL1 protein levels occurred in all the studied brain structures; the strongest upregulation was observed 24 h after trauma. Our in vitro experiments proved that primary murine microglial and astroglial cells expressed XCR1 and ITGA9, however they seemed not to be a main source of XCL1. Conclusions These findings indicate that the XCL1/XCR1 and XCL1/ITGA9 axes may participate in the development of TBI. The XCL1 can be considered as one of the triggers of secondary injury, therefore XCR1 and ITGA9 may be important targets for pharmacological intervention after traumatic brain injury. Graphic abstract

scholarly journals The selective mGluR5 agonist CHPG protects against traumatic brain injury in vitro and in vivo via ERK and Akt pathway

2011 ◽  
Vol 29 (4) ◽  
pp. 630-636 ◽  
Author(s):  
TAO CHEN ◽  
LEI ZHANG ◽  
YAN QU ◽  
KAI HUO ◽  
XIAOFAN JIANG ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Akt Pathway

scholarly journals Embedded axonal fiber tracts improve finite element model predictions of traumatic brain injury

2019 ◽  
Vol 19 (3) ◽  
pp. 1109-1130 ◽  
Author(s):  
Marzieh Hajiaghamemar ◽  
Taotao Wu ◽  
Matthew B. Panzer ◽  
Susan S. Margulies
Keyword(s):  
Traumatic Brain Injury ◽  
Finite Element ◽  
Brain Injury ◽  
Strain Rate ◽  
Brain Tissue ◽  
Brain Injuries ◽  
Characteristic Curve ◽  
Strain And Strain Rate

AbstractWith the growing rate of traumatic brain injury (TBI), there is an increasing interest in validated tools to predict and prevent brain injuries. Finite element models (FEM) are valuable tools to estimate tissue responses, predict probability of TBI, and guide the development of safety equipment. In this study, we developed and validated an anisotropic pig brain multi-scale FEM by explicitly embedding the axonal tract structures and utilized the model to simulate experimental TBI in piglets undergoing dynamic head rotations. Binary logistic regression, survival analysis with Weibull distribution, and receiver operating characteristic curve analysis, coupled with repeated k-fold cross-validation technique, were used to examine 12 FEM-derived metrics related to axonal/brain tissue strain and strain rate for predicting the presence or absence of traumatic axonal injury (TAI). All 12 metrics performed well in predicting of TAI with prediction accuracy rate of 73–90%. The axonal-based metrics outperformed their rival brain tissue-based metrics in predicting TAI. The best predictors of TAI were maximum axonal strain times strain rate (MASxSR) and its corresponding optimal fraction-based metric (AF-MASxSR7.5) that represents the fraction of axonal fibers exceeding MASxSR of 7.5 s−1. The thresholds compare favorably with tissue tolerances found in in–vitro/in–vivo measurements in the literature. In addition, the damaged volume fractions (DVF) predicted using the axonal-based metrics, especially MASxSR (DVF = 0.05–4.5%), were closer to the actual DVF obtained from histopathology (AIV = 0.02–1.65%) in comparison with the DVF predicted using the brain-related metrics (DVF = 0.11–41.2%). The methods and the results from this study can be used to improve model prediction of TBI in humans.

scholarly journals 0416 Poor Sleep Quality Predicts Serum Markers of Neurodegeneration and Cognitive Deficits in Warriors with Mild Traumatic Brain Injury

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A159-A159
Author(s):  
K Werner ◽  
P Shahim ◽  
J Gill ◽  
R Nakase-Richardson ◽  
K Kenney
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sleep Quality ◽  
Sleep Disorders ◽  
Cognitive Deficits ◽  
Neuronal Injury ◽  
Small Sample ◽  
Cross Sectional ◽  
Sleep Dysfunction ◽  
Obstructive Sleep

Abstract Introduction Increasing evidence links neurodegeneration to traumatic brain injury (TBI), and a separate body of literature links neurodegeneration to sleep dysfunction, implicating increased toxin production and decreased glymphatic clearance. Sleep disorders affect 50% of TBI patients, yet the sleep-neurodegeneration connection in these patients remains unexplored. We hypothesized that warfighters with TBI and sleep dysfunction would have increased neuronal injury, revealing potential mechanistic underpinnings for TBI outcomes. We measured plasma biomarkers, cognitive function and sleep surveys for correlation analysis. Methods In a retrospective cross-sectional study of warfighters (n=113 chronic mild TBI patients), the Pittsburgh sleep quality index (PSQI) was compared with amyloid β42 (Aβ42), neurofilament light (NFL), tau, and phospho-tau (threonine 181) isolated from plasma and exosomes. Executive function was tested with the categorical fluency test. Exosomes were precipitated from plasma. Proteins were measured with the Single Molecule Array (Quanterix). Linear models were adjusted for age, ApoE, and number of TBIs. Results Poor sleepers with TBI (PSQI>8) had elevated NFL compared to good sleepers in plasma (p=0.007) and exosomes (p=0.00017), and PSQI directly correlated with NFL (plasma: Beta=0.23, p=0.0079; exosomes: Beta=2.19, p=0.0013) stronger than any other marker of neurodegeneration. Poor sleepers also showed higher obstructive sleep apnea (OSA) risk compared to good sleepers by STOP-BANG scores (3.6, SD=1.6 vs 2.8, SD=1.74; p=0.0014) as well as decreased categorical fluency (20.7, SD=4.1) (18.3, SD=4.6, p=.0067). Plasma tau and Aβ42 also correlated with PSQI (Beta=0.64, p=0.028, and Beta=0.40, p=0.049 respectively). Conclusion This is the first reported data correlating markers of neuronal injury and cognitive deficits with sleep complaints and OSA risk in patients with TBI - possibly identifying treatable pathophysiological mediators of TBI neurodegeneration. Limitations include a small sample size, lack of objective sleep measures, and inability to establish directionality due to cross-sectional design. Prospective trials will be required to further explore our proposed hypothesis. If confirmed, these findings would call for targeting sleep disorders in the TBI population to mitigate risk of neurodegeneration. Support This work was supported by grant funding from: Department of Defense, Chronic Effects of Neurotrauma Consortium (CENC) Award W81XWH-13-2-0095 and Department of Veterans Affairs CENC Award I01 CX001135.

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