The burden and psychosocial impact on immediate caregivers of patients with spinal cord injury in a tertiary health facility,Edo State,Nigeria

Objective:This study aimed to assess the burden and psychosocial impact of spinal cord injury on the immediate caregivers at a tertiary health facility in Benin City,Edo State.Materials and Methods:A descriptive cross-sectional survey design was adopted among 73 family caregivers in the neurological ward of a tertiary health facility using a structured questionnaire as instrument of data collection.Data collected were analyzed using descriptive statistics and multiple logistic regression.Results:Findings revealed that an overall mean of 2.73 indicates that the burden on the caregivers was moderate with a moderate psychological impact(m=2.88)and a high sociological impact(m=3.12).Factors affecting the caregiving provided by immediate caregivers include social and household responsibilities(94.5%),financial situation(89.0%),family support(83.6%),and health status of the caregiver(80.8%).Age(odds ratio[OR]=5.67,95%confidence interval[CI]:1.23-27.17,P=0.027),education(OR=3.75,95%CI:1.05-13.39,P=0.041),and“others”(spouses,siblings,friends,or extended family members)(OR=3.167,95%CI:1.583-6.337,P=0.001)were predictors for high psychological impact while education(OR=0.074;95%CI:0.015-0.370,P=0.001)and caregiving role(OR=3.167;95%CI:0.1.583-6.337,P=0.001)high sociological impact.Conclusion:Majority of the caregivers experience moderate burden,moderate psychological impact,and high sociological impact.Understanding these factors is essential for developing targeted interventions and support services to address the unique needs of caregivers and mitigate the burden of caregiving on their psychosocial health.

Acute histopathological responses and long-term behavioral outcomes in mice with graded controlled cortical impact injury

While animal models of controlled cortical impact often display short-term motor dysfunction after injury, histological examinations do not show severe cortical damage. Thus, this model requires further improvement. Mice were subjected to injury at three severities using a Pin-Point^(TM)-controlled cortical impact device to establish secondary brain injury mouse models. Twenty-four hours after injury, hematoxylin-eosin staining, Fluoro-Jade B histofluorescence, and immunohistochemistry were performed for brain slices. Compared to the uninjured side, we observed differences of histopathological findings, neuronal degeneration, and glial cell number in the CA2 and CA3 regions of the hippocampus on the injured side. The Morris water maze task and beam-walking test verified long-term(14–28 days) spatial learning/memory and motor balance. To conclude, the histopathological responses were positively correlated with the degree of damage,as were the long-term behavioral manifestations after controlled cortical impact. All animal procedures were approved by the Institutional Animal Care and Use Committee at Shanghai Jiao Tong University School of Medicine.

Stability of rat models of fluid percussion-induced traumatic brain injury: comparison of three different impact forces

Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of liquid spikes. Management of impact pressure is a crucial factor that determines the stability of these models, and direction of impact control is another basic element. To improve experimental stability, we calculated a pressure curve by generating repeated impacts using a fluid percussion device at different pendulum angles. A stereotactic frame was used to control the direction of impact. We produced stable and reproducible models, including mild, moderate, and severe traumatic brain injury, using the MODEL01-B device at pendulum angles of 6°, 11° and 13°, with corresponding impact force values of 1.0 ± 0.11 atm（101.32 ± 11.16 k Pa）, 2.6 ± 0.16 atm（263.44 ± 16.21 k Pa）, and 3.6 ± 0.16 atm（364.77 ± 16.21 k Pa）, respectively. Behavioral tests, hematoxylin-eosin staining, and magnetic resonance imaging revealed that models for different degrees of injury were consistent with the clinical properties of mild, moderate, and severe craniocerebral injuries. Using this method, we established fluid percussion models for different degrees of injury and stabilized pathological features based on precise power and direction control.

Intentional and unintentional impacts of anaesthesia： insights from experiments in pain and injury

The study of brain function in the presence of pain and injury is a rapidly expanding field of experimental research.Clinically,the presence of pain and injury is often accompanied by reports of behavioural change and altered cognition.Even in a highly controlled environment such as the surgical operating theatre postoperative behavioural changes including posttraumatic stress disorder,depression,chronic fatigue,

Numerical Study on Neck Injury Under Different Postures in Vehicle Side Impact

Neck injury is a severe problem in traffic accidents.While most studies are focused on the neck injury in rear and front impacts,few are conducted in side impact.This study focuses on the difference of neck injury under different postures and the difference of 7 cervical vertebras under the same posture using the method of prescribed structure motion（PSM）.The analytical results show that the maximum changes of mean force and mean moment of 7 cervical vertebras under 8 different postures are 20% and 47% respectively.The variation of each cervical vertebra is different under different neck postures.Up cervical vertebras （C1-C4） and low cervical vertebras （C5-C7） suffer different forces and moments under the same neck posture.Generally speaking,No.6 （neck right leaning 40°） is the posture with lowest neck injury risk.

Impact of surgery on the outcome after spinal cord injury – current concepts and an outlook into the future

Traumatic spinal cord injury（SCI）remains a devastating neurological disorder leading to severe consequences for the affected individual and their families.Further,socioeconomic implications should not be neglected as well.Although life expectancy after SCI increased tremendously,therapeutic treatment options remain limited.

Endorepellin downregulation promotes angiogenesis after experimental traumatic brain injury

Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in mice.Mice were randomly divided into four groups:sham,controlled cortical impact only,adeno-associated virus(AAV)-green fluorescent protein,and AAV-shEndorepellin-green fluorescent protein groups.In the controlled cortical impact model,the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31+/Ki-67+proliferating endothelial cells and the functional microvessel density in mouse brain.These changes resulted in improved neurological function compared with controlled cortical impact mice.Western blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent protein.Synchrotron radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization,which may further improve neurobehavioral outcomes.Furthermore,an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a control.Mechanistic analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor-and angiopoietin-1-related signaling pathways.

IMPACT和CRASH模型对创伤性颅脑损伤患者预后评估价值的比较研究

背景国际颅脑损伤预后临床测试研究(IMPACT)和重型颅脑损伤后皮质类固醇的随机化研究(CRASH模型是国际上具有影响力的创伤性颅脑损伤(TBI)预后预测模型,需要继续开发,完善和持续的外部验证,以确保对不同环境的普适性。目的同时在中国TBI人群中进行验证IMPACT和CRASH模型的预后评估价值并进行比较。方法选取2017—2019年在郑州大学附属郑州中心医院内接受治疗的TBI患者210例为研究对象,收集纳入患者的基本信息。随访观察患者14 d存活情况和6个月格拉斯哥预后评分(GOS),随访截止时间为2021年6月,终止事件为中途失访。绘制受试者工作特征曲线(ROC曲线)评估IMPACT和CRASH模型对TBI患者预后的预测效能,计算ROC曲线下面积(AUC)。采用Brier评分评价模型的校准度。结果患者平均年龄(54.0±17.4)岁,分别绘制IMPACT模型与CRASH模型预测TBI患者预后的ROC曲线,结果显示IMPACT核心模型、CT模型、实验室模型预测TBI患者6个月GOS预后不良的AUC分别为0.807(95%CI=0.747~0.866,P<0.001)、0.843(95%CI=0.789~0.897,P<0.001)、0.845(95%CI=0.793~0.897,P<0.001),Brier评分分别为0.179、0.164、0.161;IMPACT核心模型、CT模型、实验室模型预测TBI患者6个月死亡的AUC分别为0.868(95%CI=0.816~0.919,P<0.001)、0.896(95%CI=0.851~0.941,P<0.001)、0.892(95%CI=0.850~0.935,P<0.001),Brier评分分别为0.151、0.144、0.136。CRASH基本模型、CT模型预测TBI患者6个月GOS预后不良的AUC分别为0.747(95%CI=0.682~0.813,P<0.001)、0.766(95%CI=0.703~0.829,P<0.001),Brier评分分别为0.306、0.308;CRASH基本模型、CT模型预测TBI患者14 d死亡的AUC分别为0.791(95%CI=0.723~0.860,P<0.001)、0.797(95%CI=0.728~0.865,P<0.001);Brier评分分别为0.348、0.383。结论对于TBI患者的预后,IMPACT模型整体较CRASH模型显示出较好的预测能力。

The pig as a preclinical traumatic brain injury model:current models,functional outcome measures,and translational detection strategies

Traumatic brain injury(TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the development of functional impairments. However, there are currently no effective therapeutic interventions that improve brain outcomes following TBI. As a result, a number of experimental TBI models have been developed to recapitulate TBI injury mechanisms and to test the efficacy of potential therapeutics. The pig model has recently come to the forefront as the pig brain is closer in size, structure, and composition to the human brain compared to traditional rodent models, making it an ideal large animal model to study TBI pathophysiology and functional outcomes. This review will focus on the shared characteristics between humans and pigs that make them ideal for modeling TBI and will review the three most common pig TBI models–the diffuse axonal injury, the controlled cortical impact, and the fluid percussion models. It will also review current advances in functional outcome assessment measures and other non-invasive, translational TBI detection and measurement tools like biomarker analysis and magnetic resonance imaging. The use of pigs as TBI models and the continued development and improvement of translational assessment modalities have made significant contributions to unraveling the complex cascade of TBI sequela and provide an important means to study potential clinically relevant therapeutic interventions.

Does progesterone show neuroprotective effects on traumatic brain injury through increasing phosphorylation of Akt in the hippocampus?

There are currently no federally approved neuroprotective agents to treat traumatic brain injury. Progesterone, a hydrophobic steroid hormone, has been shown in recent studies to exhibit neu-roprotective effects in controlled cortical impact rat models. Akt is a protein kinase known to play a role in cell signaling pathways that reduce edema, inlfammation, apoptosis, and promote cell growth in the brain. This study aims to determine if progesterone modulates the phosphor-ylation of Aktvia its threonine 308 phosphorylation site. Phosphorylation at the threonine 308 site is one of several sites responsible for activating Akt and enabling the protein kinase to carry out its neuroprotective effects. To assess the effects of progesterone on Akt phosphorylation, C57BL/6 mice were treated with progesterone （8 mg/kg） at 1 （intraperitonally）, 6, 24, and 48 hours （subcutaneously） post closed-skull traumatic brain injury. The hippocampus was harvest-ed at 72 hours post injury and prepared for western blot analysis. Traumatic brain injury caused a signiifcant decrease in Akt phosphorylation compared to sham operation. However, mice treat-ed with progesterone following traumatic brain injury had an increase in phosphorylation of Akt compared to traumatic brain injury vehicle. Our ifndings suggest that progesterone is a viable treatment option for activating neuroprotective pathways after traumatic brain injury.

Differences in pathological changes between two rat models of severe traumatic brain injury

The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans,while severe controlled cortical impact can produce a severe traumatic brain injury model using precise strike parameters.In this study,we compare the pathological mechanisms and pathological changes between two rat severe brain injury models to identify the similarities and differences.The severe controlled cortical impact model was produced by an electronic controlled cortical impact device,while the severe free weight drop model was produced by dropping a 500 g free weight from a height of 1.8 m through a plastic tube.Body temperature and mortality were recorded,and neurological deficits were assessed with the modified neurological severity score.Brain edema and bloodbrain barrier damage were evaluated by assessing brain water content and Evans blue extravasation.In addition,a cytokine array kit was used to detect inflammatory cytokines.Neuronal apoptosis in the brain and brainstem was quantified by immunofluorescence staining.Both the severe controlled cortical impact and severe free weight drop models exhibited significant neurological impairments and body temperature fluctuations.More severe motor dysfunction was observed in the severe controlled cortical impact model,while more severe cognitive dysfunction was observed in the severe free weight drop model.Brain edema,inflammatory cytokine changes and cortical neuronal apoptosis were more substantial and blood-brain barrier damage was more focal in the severe controlled cortical impact group compared with the severe free weight drop group.The severe free weight drop model presented with more significant apoptosis in the brainstem and diffused blood-brain barrier damage,with higher mortality and lower repeatability compared with the severe controlled cortical impact group.Severe brainstem damage was not found in the severe controlled cortical impact model.These results indicate that the severe controlled cortical impact model is relatively more stable,more reproducible,and shows obvious cerebral pathological changes at an earlier stage.Therefore,the severe controlled cortical impact model is likely more suitable for studies on severe focal traumatic brain injury,while the severe free weight drop model may be more apt for studies on diffuse axonal injury.All experimental procedures were approved by the Ethics Committee of Animal Experiments of Tianjin Medical University,China(approval No.IRB2012-028-02)in Febru ary 2012.

Modelling ballistic impact on military helmets:The relevance of projectile plasticity

The need to develop armour systems to protect against attacks from various sources is increasingly a matter of personal,social and national security.To develop innovative armour systems it is necessary to monitor developments being made on the type,technology and performance of the threats(weapons,projectiles,explosives,etc.) Specifically,the use of high protection level helmets on the battlefield is essential.The development of evaluation methods that can predict injuries and trauma is therefore of major importance.However,the risk of injuries or trauma that can arise from induced accelerations is an additional consideration.To develop new materials and layouts for helmets it is necessary to study the effects caused by ballistic impacts in the human head on various scenarios.The use of numerical simulation is a fundamental tool in this process.The work here presented focuses on the use of numerical simulation(finite elements analysis) to predict the consequences of bullet impacts on military helmets on human injuries.The main objectives are to assess the level and probability of head trauma using the Head Injury Criterion,caused by the impact of a 9 mm NATO projectile on a PASGT helmet and to quantify the relevance of projectile plasticity on the whole modelling process.The accelerations derived from the impact phenomenon and the deformations caused on the helmet are evaluated using fully three-dimensional models of the helmet,head,neck and projectile.Impact studies are done at impact angles ranging from 0 to 75°.Results are presented and discussed in terms of HIC and probability of acceleration induced trauma levels.Thorough comparison analyses are done using a rigid and a deformable projectile and it is observed that plastic deformation of the projectile is a significant energy dissipation mechanism in the whole impact process.

Automated monitoring of early neurobehavioral changes in mice following traumatic brain injury

Traumatic brain injury often causes a variety of behavioral and emotional impairments that can develop into chronic disorders. Therefore, there is a need to shift towards identifying early symptoms that can aid in the prediction of traumatic brain injury outcomes and behavioral endpoints in patients with traumatic brain injury after early interventions. In this study, we used the Smart Cage system, an automated quantitative approach to assess behavior alterations in mice during an early phase of traumatic brain injury in their home cages. Female C57BL/6 adult mice were subjected to moderate controlled cortical impact（CCI） injury. The mice then received a battery of behavioral assessments including neurological score, locomotor activity, sleep/wake states, and anxiety-like behaviors on days 1, 2, and 7 after CCI. Histological analysis was performed on day 7 after the last assessment. Spontaneous activities on days 1 and 2 after injury were significantly decreased in the CCI group. The average percentage of sleep time spent in both dark and light cycles were significantly higher in the CCI group than in the sham group. For anxiety-like behaviors, the time spent in a light compartment and the number of transitions between the dark/light compartments were all significantly reduced in the CCI group than in the sham group. In addition, the mice suffering from CCI exhibited a preference of staying in the dark compartment of a dark/light cage. The CCI mice showed reduced neurological score and histological abnormalities, which are well correlated to the automated behavioral assessments. Our findings demonstrate that the automated Smart Cage system provides sensitive and objective measures for early behavior changes in mice following traumatic brain injury.

Urolithin A alleviates blood-brain barrier disruption and attenuates neuronal apoptosis following traumatic brain injury in mice

Urolithin A(UA)is a natural metabolite produced from polyphenolics in foods such as pomegranates,berries,and nuts.UA is neuroprotective against Parkinson’s disease,Alzheimer’s disease,and cerebral hemorrhage.However,its effect against traumatic brain injury remains unknown.In this study,we established adult C57BL/6J mouse models of traumatic brain injury by controlled cortical impact and then intraperitoneally administered UA.We found that UA greatly reduced brain edema;increased the expression of tight junction proteins in injured cortex;increased the immunopositivity of two neuronal autophagy markers,microtubule-associated protein 1A/B light chain 3A/B(LC3)and p62;downregulated protein kinase B(Akt)and mammalian target of rapamycin(mTOR),two regulators of the phosphatidylinositol 3-kinase(PI3K)/Akt/mTOR signaling pathway;decreased the phosphorylation levels of inhibitor of NFκB(IκB)kinase alpha(IKKα)and nuclear factor kappa B(NFκB),two regulators of the neuroinflammation-related Akt/IKK/NFκB signaling pathway;reduced blood-brain barrier permeability and neuronal apoptosis in injured cortex;and improved mouse neurological function.These findings suggest that UA may be a candidate drug for the treatment of traumatic brain injury,and its neuroprotective effects may be mediated by inhibition of the PI3K/Akt/mTOR and Akt/IKK/NFκB signaling pathways,thus reducing neuroinflammation and enhancing autophagy.

Essential role of MALAT1 in reducing traumatic brain injury

As a highly evolutionary conserved long non-coding RNA,metastasis associated lung adenocarcinoma transcript 1(MALAT1)was first demonstrated to be related to lung tumor metastasis by promoting angiogenesis.To investigate the role of MALAT1 in traumatic brain injury,we established mouse models of controlled cortical impact and cell models of oxygen-glucose deprivation to mimic traumatic brain injury in vitro and in vivo.The results revealed that MALAT1 silencing in vitro inhibited endothelial cell viability and tube formation but increased migration.In MALAT1-deficient mice,endothelial cell proliferation in the injured cortex,functional vessel density and cerebral blood flow were reduced.Bioinformatic analyses and RNA pull-down assays validated enhancer of zeste homolog 2(EZH2)as a downstream factor of MALAT1 in endothelial cells.Jagged-1,the Notch homolog 1(NOTCH1)agonist,reversed the MALAT1 deficiency-mediated impairment of angiogenesis.Taken together,our results suggest that MALAT1 controls the key processes of angiogenesis following traumatic brain injury in an EZH2/NOTCH1-dependent manner.

Temporal changes in inflammatory mitochondria-enriched microRNAs following traumatic brain injury and effects of miR-146a nanoparticle delivery

MicroRNAs(miRNAs)are small non-coding RNA molecules that regulate post-transcriptional gene expression and contribute to all aspects of cellular function.We previously reported that the activities of several mitochondria-enriched miRNAs regulating inflammation(i.e.,miR-142-3p,miR-142-5p,and miR-146a)are altered in the hippocampus at 3–12 hours following a severe traumatic brain injury.In the present study,we investigated the temporal expression profile of these inflammatory miRNAs in mitochondria and cytosol fractions at more chronic post-injury times following severe controlled cortical impact injury in rats.In addition,several inflammatory genes were analyzed in the cytosol fractions.The analysis showed that while elevated levels were observed in cytoplasm,the mitochondria-enriched miRNAs,miR-142-3p and miR-142-5p continued to be significantly reduced in mitochondria from injured hippocampi for at least 3 days and returned to near normal levels at 7 days post-injury.Although not statistically significant,miR-146a also remained at reduced levels for up to 3 days following controlled cortical impact injury,and recovered by 7 days.In contrast,miRNAs that are not enriched in mitochondria,including miR-124a,miR-150,miR-19b,miR-155,and miR-223 were either increased or demonstrated no change in their levels in mitochondrial fractions for 7 days.The one exception was that miR-223 levels were reduced in mitochondria at 1 day following injury.No major alterations were observed in sham operated animals.This temporal pattern was unique to mitochondria-enriched miRNAs and correlated with injury-induced changes in mitochondrial bioenergetics as well as expression levels of several inflammatory markers.These observations suggested a potential compartmental re-distribution of the mitochondria-enriched inflammatory miRNAs and may reflect an intracellular mechanism by which specific miRNAs regulate injury-induced inflammatory signaling.To test this,we utilized a novel peptide-based nanoparticle strategy for in vitro and in vivo delivery of a miR-146a mimic as a potential therapeutic strategy for targeting nuclear factor-kappa B inflammatory modulators in the injured brain.Nanoparticle delivery of miR-146a to BV-2 or SH-SY5Y cells significantly reduced expression of TNF receptor-associated factor 6(TRAF6)and interleukin-1 receptor-associated kinase 1(IRAK1),two important modulators of the nuclear factor-kappa B(NF-κB)pro-inflammatory pathway.Moreover,injections of miR-146a containing nanoparticles into the brain immediately following controlled cortical impact injury significantly reduced hippocampal TNF receptor-associated factor 6 and interleukin-1 receptor-associated kinase 1 levels.Taken together,our studies demonstrate the subcellular alteration of inflammatory miRNAs after traumatic brain injury and establish proof of principle that nanoparticle delivery of miR-146a has therapeutic potential for modulating pro-inflammatory effectors in the injured brain.All of the studies performed were approved by the University of Kentucky Institutional Animal Care and Usage Committee(IACUC protocol#2014-1300)on August 17,2017.

Identification of predictive MRI and functional biomarkers in a pediatric piglet traumatic brain injury model

Traumatic brain injury(TBI) at a young age can lead to the development of long-term functional impairments. Severity of injury is well demonstrated to have a strong influence on the extent of functional impairments;however, identification of specific magnetic resonance imaging(MRI) biomarkers that are most reflective of injury severity and functional prognosis remain elusive. Therefore, the objective of this study was to utilize advanced statistical approaches to identify clinically relevant MRI biomarkers and predict functional outcomes using MRI metrics in a translational large animal piglet TBI model. TBI was induced via controlled cortical impact and multiparametric MRI was performed at 24 hours and 12 weeks post-TBI using T1-weighted, T2-weighted, T2-weighted fluid attenuated inversion recovery, diffusion-weighted imaging, and diffusion tensor imaging. Changes in spatiotemporal gait parameters were also assessed using an automated gait mat at 24 hours and 12 weeks post-TBI. Principal component analysis was performed to determine the MRI metrics and spatiotemporal gait parameters that explain the largest sources of variation within the datasets. We found that linear combinations of lesion size and midline shift acquired using T2-weighted imaging explained most of the variability of the data at both 24 hours and 12 weeks post-TBI. In addition, linear combinations of velocity, cadence, and stride length were found to explain most of the gait data variability at 24 hours and 12 weeks post-TBI. Linear regression analysis was performed to determine if MRI metrics are predictive of changes in gait. We found that both lesion size and midline shift are significantly correlated with decreases in stride and step length. These results from this study provide an important first step at identifying relevant MRI and functional biomarkers that are predictive of functional outcomes in a clinically relevant piglet TBI model. This study was approved by the University of Georgia Institutional Animal Care and Use Committee(AUP: A2015 11-001) on December 22, 2015.

Analysis of Vehicle Seat and Research on Structure Optimization in Front and Rear Impact

This paper used the Hyper Mesh and LS-DYNA software to establish a dummy-seat finite element simulation model. The head, chest and neck injury of the dummy were analyzed respectively in the frontal impact and rear impact. It was indicated that modification of seat was needed to meet the requirements. The simulation results showed that the original model cannot provide effective protection for the occupants and need for structural improvements. According to the simulation results of deformation and stress conditions of the seat parts, the original seat structure was improved and optimized for four improvement schemes, including the structure optimization of the seat side panel, the center hinge, framework under the cushion and the backrest lock. The results indicated that the optimized seat improved the occupant protection performance by reducing occupant damage parameters compared with original seat, which illustrated that the optimization basically met the target.

Acute effects of human protein S administration after traumatic brain injury in mice

Despite years of effort,no effective acute phase treatment has been discovered for traumatic brain injury.One impediment to successful drug development is entangled secondary injury pathways.Here we show that protein S,a natural multifunctional protein that regulates coagulation,inflammation,and apoptosis,is able to reduce the extent of multiple secondary injuries in traumatic brain injury,and therefore improve prognosis.Mice subjected to controlled cortical impact were treated acutely(10–15 minutes post-injury)with a single dose of either protein S(1 mg/kg)or vehicle phosphate buffered saline via intravenous injection.At 24 hours post-injury,compared to the non-treated group,the protein S treated group showed substantial improvement of edema and fine motor coordination,as well as mitigation of progressive tissue loss.Immunohistochemistry and western blot targeting caspase-3,B-cell lymphoma 2(Bcl-2)along with terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay revealed that apoptosis was suppressed in treated animals.Immunohistochemistry targeting CD11 b showed limited leukocyte infiltration in the protein S-treated group.Moreover,protein S treatment increased the ipsilesional expression of aquaporin-4,which may be the underlying mechanism of its function in reducing edema.These results indicate that immediate intravenous protein S treatment after controlled cortical impact is beneficial to traumatic brain injury prognosis.Animal Use Protocols(AUPs)were approved by the University Committee on Animal Resources(UCAR)of University of Rochester Medical Center(approval No.UCAR-2008-102 R)on November 12,2013.

Use of Finite Element Analysis for the Prediction of Driver Fatality Ratio Based on Vehicle Intrusion Ratio in Head-On Collisions

To estimate the aggressivity of vehicles in frontal crashes, national highway traffic safety administration (NHTSA) has introduced the driver fatality ratio, DFR, for different vehicle-to-vehicle categories. The DFR proposed by NHTSA is based on the actual crash statistical data, which makes it difficult to evaluate for other vehicle categories newly introduced to the market, as they do not have sufficient crash statistics. A finite element (FE) methodology is proposed in this study based on computational reconstruction of crashes and some objective measures to predict the relative risk of DFR associated with any vehicle-to-vehicle crash. The suggested objective measures include the ratios of maximum intrusion in the passenger compartments of the vehicles in crash, and the transmitted peak deceleration of the vehicles’ center of gravity, which are identified as the main influencing parameters on occupant injury. The suitability of the proposed method is established for a range of bullet light truck and van (LTV) categories against a small target passenger car with published data by NHTSA. A mathematical relation between the objective measures and DFR is then developed. The methodology is then extended to predict the relative risk of DFR for a crossover category vehicle, a light pick-up truck, and a mid-size car in crash against a small size passenger car. It is observed that the ratio of intrusions produces a reasonable estimate for the DFR, and that it can be utilized in predicting the relative risk of fatality ratios in head-on collisions. The FE methodology proposed in this study can be utilized in design process of a vehicle to reduce the aggressivity of the vehicle and to increase the on-road fleet compatibility in order to reduce the occupant injury out- come.