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 A new function for Prokineticin 2: recruitment of SVZ-derived neuroblasts to the injured cortex in a mouse model of traumatic brain injury

2018 ◽  
Author(s):  
Mayara Vieira Mundim ◽  
Laura Nicoleti Zamproni ◽  
Agnes Araújo Sardinha Pinto ◽  
Layla Testa Galindo ◽  
André Machado Xavier ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Subventricular Zone ◽  
Brain Injuries ◽  
Rostral Migratory Stream ◽  
Subgranular Zone ◽  
Prokineticin 2 ◽  
Migratory Stream

AbstractTraumatic brain injury is an important cause of mortality and morbidity all over the world. After the initial injury there is a cascade of cellular and molecular events that ultimately lead to cell death. Therapies aim not only to counteract these mechanisms but also to replenish the lost cell population in order to achieve a better recovery. The adult mammal brain in not as plastic as the postnatal, but it has at least two neurogenic regions that maintains physiological functions in the brain; the subgranular zone of the dentate gyrus of the hippocampus, which produces neurons that integrate locally, and the subventricular zone (SVZ) of the lateral ventricles, that produces neuroblasts that migrate through the rostral migratory stream (RMS) to the olfactory bulbs. Brain injuries, as well as neurodegenerative diseases, induce the SVZ to respond by increasing cell proliferation and migration to the injured areas. Here we report that SVZ cells migrate to the injured cortex after traumatic brain injury in mice, and that the physiological RMS migration is not impaired. We also show that Prokineticin 2 (PROK2), a chemokine important for the olfactory bulb neurogenesis by promoting the directional migration of neuroblasts, is induced in the injured cortex. Using PROK2 receptor antagonist and recombinant PROK2 we show for the first time that PROK2 can directionally attract SVZ cells in vitro and in vivo. The data we present here links one more element of the inflammatory process, PROK2 secreted by microglia, to the attempt to regenerate an acutely injured mammalian cortex.AbbreviationsSGZsubgranular zoneSVZsubventricular zoneRMSrostral migratory streamPROK2Prokineticin 2

Blast Traumatic Brain Injury Mechanisms

Neurotrauma ◽  
2018 ◽  
pp. 111-122
Author(s):  
Elizabeth McNeil ◽  
Zachary Bailey ◽  
Allison Guettler ◽  
Pamela VandeVord
Keyword(s):  
Traumatic Brain Injury ◽  
Finite Element ◽  
Brain Injury ◽  
Head Injury ◽  
Mechanism Of Injury ◽  
Primary Blast ◽  
Blast Traumatic Brain Injury ◽  
Injury Mechanisms ◽  
Biomechanical Investigation

Blast traumatic brain injury (bTBI) is a leading cause of head injury in soldiers returning from the battlefield. Primary blast brain injury remains controversial with little evidence to support a primary mechanism of injury. The four main theories described herein include blast wave transmission through skull orifices, direct cranial transmission, thoracic surge, and skull flexure dynamics. It is possible that these mechanisms do not occur exclusively from each other, but rather that several of them lead to primary blast brain injury. Biomechanical investigation with in-vivo, cadaver, and finite element models would greatly increase our understanding of bTBI mechanisms.

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 Glycolytic inhibitor 2-deoxyglucose prevents cortical hyperexcitability after traumatic brain injury

2018 ◽  
Author(s):  
Jenny B. Koenig ◽  
David Cantu ◽  
Cho Low ◽  
Farzad Noubary ◽  
Danielle Croker ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Epileptiform Activity ◽  
Synaptic Activity ◽  
Network Function ◽  
Cortical Hyperexcitability ◽  
Glycolytic Inhibitor ◽  
Cortical Slices

AbstractTraumatic brain injury (TBI) causes cortical dysfunction and can lead to post-traumatic epilepsy. Multiple studies demonstrate that GABAergic inhibitory network function is compromised following TBI, which may contribute to hyperexcitability and motor, behavioral, and cognitive deficits. Preserving the function of GABAergic interneurons, therefore, is a rational therapeutic strategy to preserve cortical function after TBI and prevent long-term clinical complications. Here, we explored an approach based on the ketogenic diet, a neuroprotective and anticonvulsant dietary therapy which results in reduced glycolysis and increased ketosis. Utilizing a pharmacologic inhibitor of glycolysis (2-deoxyglucose, or 2-DG), we found that acute in vitro glycolytic inhibition decreased the excitability of excitatory neurons, but not inhibitory interneurons, in cortical slices from naïve mice. Employing the controlled cortical impact (CCI) model of TBI in mice, we found that in vitro 2-DG treatment rapidly attenuated epileptiform activity seen in acute cortical slices 3-5 weeks after TBI. One week of in vivo 2-DG treatment immediately after TBI prevented the development of epileptiform activity, restored excitatory and inhibitory synaptic activity, and attenuated loss of parvalbumin-positive inhibitory interneurons. In summary, inhibition of glycolysis with 2-DG may have therapeutic potential to restore network function following TBI.One Sentence SummaryFollowing traumatic brain injury in mice, in vivo treatment with the glycolytic inhibitor 2-deoxyglucose prevented cortical network pathology including cortical hyperexcitability, changes in synaptic activity, and loss of parvalbumin-expressing GABAergic interneurons.

scholarly journals The TRIM protein Mitsugumin 53 enhances survival and therapeutic efficacy of stem cells in murine traumatic brain injury

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Fangxia Guan ◽  
Tuanjie Huang ◽  
Xinxin Wang ◽  
Qu Xing ◽  
Kristyn Gumpper ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Brain Injury ◽  
Therapeutic Efficacy ◽  
Brain Dysfunction ◽  
Vital Role ◽  
Neurological Deficits ◽  
Human Umbilical Cord

Abstract Background Traumatic brain injury (TBI) is a common neurotrauma leading to brain dysfunction and death. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold promise in the treatment of TBI. However, their efficacy is modest due to low survival and differentiation under the harsh microenvironment of the injured brain. MG53, a member of TRIM family protein, plays a vital role in cell and tissue damage repair. The present study aims to test whether MG53 preserves hUC-MSCs against oxidative stress and enhances stem cell survival and efficacy in TBI treatment. Methods In this study, we performed a series of in vitro and in vivo experiments in hUC-MSCs and mice to define the function of MG53 enhancing survival, neurogenesis, and therapeutic efficacy of stem cells in murine traumatic brain injury. Results We found that recombinant human MG53 (rhMG53) protein protected hUC-MSCs against H2O2-induced oxidative damage and stimulated hUC-MSC proliferation and migration. In a mouse model of contusion-induced TBI, intravenous administration of MG53 protein preserved the survival of transplanted hUC-MSCs, mitigated brain edema, reduced neurological deficits, and relieved anxiety and depressive-like behaviors. Co-treatment of MG53 and hUC-MSCs enhanced neurogenesis by reducing apoptosis and improving PI3K/Akt-GSK3β signaling. Conclusion MG53 enhances the efficacy of hUC-MSCs in the recovery of TBI, indicating that such adjunctive therapy may provide a novel strategy to lessen damage and optimize recovery for brain injury.

scholarly journals Hyaluronidase reduced edema after experimental traumatic brain injury

2019 ◽  
Vol 40 (10) ◽  
pp. 2026-2037 ◽  
Author(s):  
Patricia M Washington ◽  
Changhee Lee ◽  
Mary Kate R Dwyer ◽  
Elisa E Konofagou ◽  
Steven G Kernie ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Magnetic Resonance ◽  
Charge Density ◽  
Fixed Charge ◽  
Resonance Imaging ◽  
Fixed Charge Density

Cerebral edema and the subsequent increased intracranial pressure are associated with mortality and poor outcome following traumatic brain injury. Previous in vitro studies have shown that the Gibbs-Donnan effect, which describes the tendency of a porous, negatively charged matrix to attract positive ions and water, applies to brain tissue and that enzymatic reduction of the fixed charge density can prevent tissue swelling. We tested whether hyaluronidase, an enzyme that degrades the large, negatively charged glycosaminoglycan hyaluronan, could reduce brain edema after traumatic brain injury. In vivo, intracerebroventricular injection of hyaluronidase after controlled cortical impact in mice reduced edema in the ipsilateral hippocampus at 24 h by both the wet-weight/dry-weight method (78.15 ± 0.65% vs. 80.4 ± 0.46%; p < 0.01) and T2-weighted magnetic resonance imaging (13.88 ± 3.09% vs. 29.23 ± 6.14%; p < 0.01). Hyaluronidase did not adversely affect blood–brain-barrier-integrity measured by dynamic contrast-enhanced magnetic resonance imaging, nor did hyaluronidase negatively affect functional recovery after controlled cortical impact measured with the rotarod or Morris water maze tasks. Reduction of fixed charge density by hyaluronidase was confirmed in cortical explants in vitro (5.46 ± 1.15 µg/mg vs. 7.76 ± 1.87 µg/mg; p < 0.05). These data demonstrate that targeting the fixed charge density with hyaluronidase reduced edema in an in vivo mouse model of traumatic brain injury.

Brain tissue oxygen monitoring after severe traumatic brain injury in children: relationship to outcome and association with other clinical parameters

2012 ◽  
Vol 10 (5) ◽  
pp. 383-391 ◽  
Author(s):  
Martina Stippler ◽  
Veronica Ortiz ◽  
P. David Adelson ◽  
Yue-Fang Chang ◽  
Elizabeth C. Tyler-Kabara ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Partial Pressure ◽  
Brain Tissue ◽  
Neurological Outcome ◽  
Brain Injuries ◽  
Brain Temperature ◽  
Clinical Variables ◽  
Arterial Blood ◽  
Favorable Neurological Outcome

Object Minimizing secondary brain injuries after traumatic brain injury (TBI) in children is critical to maximizing neurological outcome. Brain tissue oxygenation monitoring (as measured by interstitial partial pressure of O2 [PbO2]) is a new tool that may aid in guiding therapies, yet experience in children is limited. This study aims to describe the authors' experience of PbO2 monitoring after TBI. It was hypothesized that PbO2 thresholds could be established that were associated with favorable neurological outcome, and it was determined whether any relationships between PbO2 and other important clinical variables existed. Methods Forty-six children with severe TBI (Glasgow Coma Scale score ≤ 8 after resuscitation) who underwent PbO2 and brain temperature monitoring between September 2004 and June 2008 were studied. All patients received standard neurocritical care, and 24 were concurrently enrolled in a trial of therapeutic early hypothermia (n = 12/group). The PbO2 was measured in the uninjured frontal cortex. Hourly recordings and calculated daily means of various variables including PbO2, intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial blood pressure, partial pressure of arterial O2, and fraction of inspired O2 were compared using several statistical approaches. Glasgow Outcome Scale scores were determined at 6 months after injury. Results The mean patient age was 9.4 years (range 0.1–16.5 years; 13 girls) and 8554 hours of monitoring were analyzed (PbO2 range 0.0–97.2 mm Hg). A PbO2 of 30 mm Hg was associated with the highest sensitivity/specificity for favorable neurological outcome at 6 months after TBI, yet CPP was the only factor that was independently associated with favorable outcome. Surprisingly, instances of preserved PbO2 with altered ICP and CPP were observed in some children with unfavorable outcomes. Conclusions Monitoring of PbO2 demonstrated complex interactions with clinical variables reflecting intracranial dynamics using this protocol. A higher threshold than reported in studies in adults was suggested as a potential therapeutic target, but this threshold was not associated with improved outcomes. Additional studies to assess the utility of PbO2 monitoring after TBI in children are needed.

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