Search

Abstract: Schroeder, LH, McDaniel, AT, Wang, Y, Dickens, GM, Pantani, V, and Kubinak, H. Evaluating neck-strengthening protocols to reduce the incidence of traumatic brain injury: traditional vs. nontraditional neck-strengthening techniques. J Strength Cond Res 38(7): 1266-1274, 2024-A common cause of traumatic brain injuries (TBIs) is the head's kinematic response to rapid movement, which can be reduced with dynamic neck strengthening. This study aimed to determine the most effective neck-strengthening program by comparing a traditional and nontraditional program. Isometric neck strength was assessed in 32 subjects randomly assigned to one of the traditional and nontraditional neck-strengthening programs. The nontraditional program used a novel neck-strengthening device. After weeks 6 and 10 of training, isometric neck strength was reassessed. With the collected data, linear mixed models were established to compare the changes in neck strength between the 2 groups during the 10-week training period. Statistical analysis results suggest that, for both cervical extension (CE) and cervical flexion (CF), subjects in the novel neck-strengthening device group had a significantly higher gain of strength during the 10 weeks than the traditional group. With test statistics of -2.691 and -3.203 and corresponding 2-sided p -value of 0.01289 and 0.003889, respectively, we conclude that there is a statistically significant difference in the linear slopes of increase for both CE and CF between the 2 groups. As to left cervical lateral flexion and right cervical lateral flexion, the novel neck strength group had increased strength gains compared with the traditional group. However, the increase was not enough to demonstrate significant findings. Results were considered significant at p < 0.05. The results of this study show that the novel neck-strengthening device may be an effective mechanism for preventing mild TBIs., (Copyright © 2023 National Strength and Conditioning Association.)

Head impacts in bicycle accidents are typically oblique to the impact surface and transmit both normal and tangential forces to the head, causing linear and rotational head kinematics, respectively. Traditional expanded polystyrene (EPS) foam bicycle helmets are effective at preventing many head injuries, especially skull fractures and severe traumatic brain injuries (TBIs) (primarily from normal contact forces). However, the incidence of concussion from collisions (primarily from rotational head motion) remains high, indicating need for enhanced protection. An elastomeric honeycomb helmet design is proposed herein as an alternative to EPS foam to improve TBI protection and be potentially reusable for multiple impacts, and tested using a twin-wire drop tower. Small-scale normal and oblique impact tests showed honeycomb had lower oblique strength than EPS foam, beneficial for diffuse TBI protection by permitting greater shear deformation and had the potential to be reusable. Honeycomb helmets were developed based on the geometry of an existing EPS foam helmet, prototypes were three-dimensional-printed with thermoplastic polyurethane and full-scale flat and oblique drop tests were performed. In flat impacts, honeycomb helmets resulted in a 34% higher peak linear acceleration and 7% lower head injury criteria (HIC15) than EPS foam helmets. In oblique tests, honeycomb helmets resulted in a 30% lower HIC15 and 40% lower peak rotational acceleration compared to EPS foam helmets. This new helmet design has the potential to reduce the risk of TBI in a bicycle accident, and as such, reduce its social and economic burden. Also, the honeycomb design showed potential to be effective for repetitive impact events without the need for replacement, offering benefits to consumers., (Copyright © 2024 by ASME.)

Background: Wearing protective helmets is an important prevention strategy to reduce work-related traumatic brain injuries. The existing standardized testing systems are used for quality control and do not provide a quantitative measure of the helmet performance., Objective: To analyze the failure characterizations of Type I industrial helmets and develop a generalized approach to quantify the shock absorption performance of Type I industrial helmets based on the existing standardized setups., Methods: A representative basic Type I construction helmet model was selected for the study. Top impact tests were performed on the helmets at different drop heights using two different impactor masses (3.6 and 5.0 kg)., Results: When the helmets were impacted with potential impact energies smaller than the critical potential impact energy values, there was a consistent relationship between the peak impact force and the potential impact energy. When the helmets were impacted under potential impact energies greater than the critical potential impact energy values, the peak impact forces increased steeply with increasing potential impact energy., Conclusion: A concept of safety margin for construction helmets based on potential impact energy was introduced to quantify the helmets' shock absorption performance. The proposed method will help helmet manufacturers improve their product quality.

Traumatic brain injury (TBI) represents a considerable portion of the global injury burden. The incidence of TBI will continue to increase in view of an increase in population density, an aging population, and the increased use of motor vehicles, motorcycles, and bicycles. The most common causes of TBI are falls and road traffic injuries. Deaths related to road traffic injury are three times higher in low-and middle-income countries (LMIC) than in high-income countries (HIC). The Latin American Caribbean region has the highest incidence of TBI worldwide, primarily caused by road traffic injuries. Data from HIC indicates that road traffic injuries can be successfully prevented through concerted efforts at the national level, with coordinated and multisector responses to the problem. Such actions require implementation of proven measures to address the safety of road users and the vehicles themselves, road infrastructure, and post-crash care. In this review, we focus on the epidemiology of TBI in Latin America and the implementation of solutions and preventive measures to decrease mortality and long-term disability., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Environmental enrichment (EE) confers significant increases in neurobehavioral and cognitive recovery and decreases histological damage in various models of traumatic brain injury (TBI). However, despite EE's pervasiveness, little is known regarding its prophylactic potential. Thus, the goal of the current study was to determine whether enriching rats prior to a controlled cortical impact exerts protection as evidenced by attenuated injury-induced neurobehavioral and histological deficits relative to rats without prior EE. The hypothesis was that enrichment prior to TBI would be protective. After two weeks of EE or standard (STD) housing, anesthetized adult male rats received either a controlled cortical impact (2.8 mm deformation at 4 m/s) or sham injury and then were placed in EE or STD conditions. Motor (beam-walk) and cognitive (spatial learning) performance were assessed on post-operative days 1-5 and 14-18, respectively. Cortical lesion volume was quantified on day 21. The group that was housed in STD conditions before TBI and received post-injury EE performed significantly better in motor, cognitive, and histological outcomes vs. both groups in STD conditions regardless of whether having received pre-injury EE or not (p < 0.05). That no differences in any endpoint were revealed between the two STD-housed groups after TBI suggests that enriching rats prior to TBI does not attenuate neurobehavioral or histological deficits and therefore does not support the hypothesis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of interests No funding was provided specifically for this Commission paper; however, most authors are involved in the International Initiative for Traumatic Brain Injury Research (InTBIR) as a scientific participant or an investigator. This Commission would not have been possible without the indirect facilitation provided by the InTBIR network. AIRM declares consulting fees from PresSura Neuro, Integra Life Sciences, and NeuroTrauma Sciences. DKM reports research support, and educational and consulting fees from Lantmannen AB, GlaxoSmithKline, Calico, PresSura Neuro, NeuroTrauma Sciences, and Integra Neurosciences. GTM declares grants from the US National Institutes of Health-National Institute of Neurological Disorders and Stroke (grant U01NS086090), the US Department of Defense (grant W81XWH-14-2-0176, grant W81XWH-18-2-0042, and contract W81XWH-15-9-0001). MC reports licensing fees for ICM+ software from Cambridge Enterprise and was an honorary (unpaid) director for Medicam. PS reports licensing fees for ICM+ software from Cambridge Enterprise. MBS has in the past 3 years received consulting income from Acadia Pharmaceuticals, Aptinyx, atai Life Sciences, Boehringer Ingelheim, Bionomics, BioXcel Therapeutics, Clexio, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, and Roche/Genentech. MBS also has stock options in Oxeia Biopharmaceuticals and EpiVario and is paid for editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). KKWW holds stock options in Gryphon Bio. All other authors declare no competing interests.

Background: While motorcycle helmets reduce mortality and morbidity, no guidelines specify which is safest. We sought to determine if full-face helmets reduce injury and death., Methods: We searched for studies without exclusion based on: age, language, date, or randomization. Case reports, professional riders, and studies without original data were excluded. Pooled results were reported as OR (95% CI). Risk of bias and certainty was assessed. (PROSPERO #CRD42021226929)., Results: Of 4431 studies identified, 3074 were duplicates, leaving 1357 that were screened. Eighty-one full texts were assessed for eligibility, with 37 studies (n = 37,233) eventually included. Full-face helmets reduced traumatic brain injury (OR 0.40 [0.23-0.70]); injury severity for the head and neck (Abbreviated Injury Scale [AIS] mean difference -0.64 [-1.10 to -0.18]) and face (AIS mean difference -0.49 [-0.71 to -0.27]); and facial fracture (OR 0.26 [0.15-0.46])., Conclusion: Full-face motorcycle helmets are conditionally recommended to reduce traumatic brain injury, facial fractures, and injury severity., Competing Interests: Declaration of competing interest ZMB is a paid educational consultant for Zimmer-Biomet and KLS-Martin for areas unrelated to the current study., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Modern military combat helmets vary in their shapes and features, but all are designed to protect the head from traumatic brain injury. Recent recommendations for protection against energised projectiles that are characteristic of secondary blast injury is to ensure coverage of both the brain and brainstem., Method: Graphical representations of essential coverage of the head (cerebral hemispheres, cerebellum and brainstem) within an anthropometrically sized model were superimposed over two standard coverage helmets (VIRTUS helmet, Advanced Combat Helmet (ACH)) and two 'high-cut' helmets (a Dismounted Combat Helmet (DCH)) and Combat Vehicle Crewman (CVC) helmet), both of which are designed to be worn with communications devices. Objective shotline coverage from representative directions of projectile travel (-30 to +30 degrees) was determined using the Coverage of Armour Tool (COAT)., Results: VIRTUS and ACH demonstrated similar overall coverage (68.7% and 69.5%, respectively), reflecting their similar shell shapes. ACH has improved coverage from below compared with VIRTUS (23.3% vs 21.7%) due to its decreased standoff from the scalp. The 'high-cut' helmets (DCH and CVC) had reduced overall coverage (57.9% and 52.1%), which was most pronounced from the side., Conclusions: Both the VIRTUS and ACH helmets provide excellent overall coverage of the brain and brainstem against ballistic threats. Coverage of both would be improved at the rear by using a nape protector and the front using a visor. This is demonstrated with the analysis of the addition of the nape protector in the VIRTUS system. High-cut helmets provide significantly reduced coverage from the side of the head, as the communication devices they are worn with are not designed to provide protection from ballistic threats. Unless absolutely necessary, it is therefore recommended that high-cut helmets be worn only by those users with defined specific requirements, or where the risk of injury from secondary blast is low., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

India has one of the highest TBI burdens due to road traffic accidents (RTAs), with 60% of head injuries being attributable to RTA and more than 150,000 lives being lost annually due to traumatic brain injury (TBI). These numbers have prompted institutions and organizations at international, national, and local levels to mobilize and address this burden through prevention, prehospital care, and in hospital care. Academic institutions such as Andhra Medical College have run local campaigns promoting the wearing of helmets when riding 2-wheelers. Prehospital care institutions such as Gunupati Venkata Krishna - Emergency Management and Research Institute have also made large strides nationally on delivering safe and timely care through novel and focused education to its emergency medical technicians, applying evidence-based practice to all facets of its work. These changes led to implementation of novel and innovative technological solutions for faster and more efficient responses. National institutions such as the Neurological Society of India (NSI) and Neurotrauma Society of India (NTSI) have been instrumental in promoting safety measures such as use of helmets and seatbelts through social media videos, often using celebrities to disseminate the message. NSI have also focused on sharing best practices for the management of TBI through easy-to-use platforms such as YouTube. Institutions such as American Association of Physicians of Indian Origin, NSI, and NTSI have collaboratively developed TBI management guidelines that are specific to the Indian population (supported by American Association of South Asian Neurosurgeons). Non-governmental organizations such as the Indian Head Injury Foundation and Save Life Foundation have contributed to this movement by promoting awareness through campaigns and public education. While TBI remains a large burden in India, a mobilization and coalesced efforts of such a scale holds promise for tackling this burden., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Recreational activities and sports are a common and popular way for youth to enjoy physical activity; however, there are risks related to physical injury. Injuries can potentially result in death and long-term disability, especially from traumatic brain injury. Helmet use can significantly decrease the risk of fatal and nonfatal head injury, including severe traumatic brain injury and facial injuries when participating in recreational sports. The most robust evidence of helmet effectiveness has been demonstrated with bicycling and snow sports (eg, skiing, snowboarding). Despite this evidence, helmets are not worn consistently with all recreational sports. A multipronged approach is necessary to increase helmet use by children and youth participating in recreational sports. This approach includes legislation and enforcement, public educational campaigns, child education programs, and anticipatory guidance from clinicians. This policy statement guides clinicians, public health advocates, and policymakers on best practices for increasing helmet use in recreational sports, including bicycling and snow sports., Competing Interests: FINANCIAL/CONFLICT OF INTEREST DISCLOSURES: None., (Copyright © 2022 by the American Academy of Pediatrics.)

Purpose: Bicycle accidents are potentially preventable, and helmets can mitigate the severity of injuries. The purpose of the study it to investigate geo-demographic areas to establish prevention policies and targeted programs., Methods: From October 2013 to March 2020 all bicycle injuries at a Level 1 trauma center were collected for ages ≤18 years. Demographics, injuries, and outcomes were analyzed. Incidents were aggregated to zip codes and the Local Indicators of Spatial Association (LISA) statistic was used to test for spatial clustering of injury rates per 10,000 children., Results: Over the 8-year time period, 77 cases were identified with an average age of 13±4 years, 83% male and 48% non-Hispanic white. The majority of patients (98%) were not wearing a helmet. Loss of consciousness was reported in 44% and 21% sustained a traumatic brain injury. Twenty-eight percent required ICU care and 36% required operative interventions. There was only 1 mortality in the cohort (<1%).Injuries were more common in lower household income zip codes (Figure 1). Six zip codes encompassing several interstate exits and the connected heavy-traffic roadways comprise a statistically significant cluster of pediatric bicycle accidents (Figure 1)., Conclusion: Low-income neighborhoods and those near major roadways held the highest risk for pediatric bicycle accidents. Use of helmets was extremely low in the patient population, with high rates of traumatic brain injury. With this information, targeted programs to address high-risk intersections, helmet access, and safety education can be implemented locally., (Copyright © 2022. Published by Elsevier Inc.)

Background: The Caribbean is a unique region of islands and cays home to nearly 43 million people. A significant challenge facing this population is the burden of traumatic brain injury, which disproportionately affects younger individuals and carries a significant economic burden. A preventive measure to reduce this burden is consistent wearing of helmets. This study aims to assess TBI prevention through helmet safety in Caribbean nations in order to demonstrate the regional impact of public health solutions., Methods: We assess the member states of the Caribbean Community (CARICOM) and sought to evaluate CARICOM nations' TBI prevention through helmet safety with relation to public health, policy, laws, infrastructure, and regulations. We produced the Rolle Scoring System (RSS) to ascertain the influence of governance around helmet safety for TBI prevention. The RSS aims to provide a quantifiable method of how well a CARICOM nation is performing in efforts to reduce TBI. The RSS is broken down into 2 categories, with scores ranging from 1 (worst) to 5 (best). The range of possible scores a CARICOM nation could receive was 8 to 40., Results: Fourteen CARICOM nations were ultimately incorporated into our analysis. From the initial cohort, 3 were removed. These nations were Anguilla, Saint Kitts & Nevis, and Montserrat. We analyzed values derived from the RSS, finding a mean Rolle score of 22. We further subdivided the nations into low Rolle score (8-24) and high Rolle score (>24). Trinidad and Tobago had the highest Rolle score at 29. Haiti was found to have the lowest Rolle score at 8., Conclusion: Several Caribbean nations have demonstrated leadership pertaining to TBI prevention through helmet safety. The regional momentum of helmet safety in the Caribbean can serve as a model for other geographical regional blocs that share interests and culture to consider comprehensive approaches to public health challenges., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Traumatic brain injury is the alteration in brain function due to an external force. It is common and affects millions of people worldwide annually. The World Health Organization estimates that 90% of global deaths caused by injuries occur in low- and middle-income countries, with traumatic brain injury contributing up to half of these trauma-related deaths. Patients with traumatic brain injury in low- and middle-income countries have twice the odds of dying compared with their counterparts in high-income countries. Sedation is a key element of care in the management of traumatic brain injury, used for its neuroprotective effects and to prevent secondary brain injury. While sedatives have the potential to improve outcomes, they can be challenging to administer and have potentially dangerous complications. Sedation in low-resource settings should aim to be effective, safe, affordable and feasible. In this paper, we summarise the indications for sedation in traumatic brain injury, the choice of sedative drugs and the pragmatic management and monitoring of sedated traumatic brain injury patients in low-resource settings., (© 2022 Association of Anaesthetists.)

Background: Neurotrauma is a leading cause of morbidity and mortality around the world. Assessment of injury prevention and prehospital care for neurotrauma patients is necessary to improve care systems., Methods: A 29-question electronic survey was developed based on the Enhancing the Quality and Transparency Of health Research (EQUATOR) checklist to assess neurotrauma policies and laws related to safety precautions. The survey was distributed to members of World Health Organization regions that were considered to be experienced medical authorities in neurosurgery and traumatic brain injury., Results: There were 82 (39%) responses representing 46 countries. Almost all respondents (95.2%) were within the neurosurgical field. Of respondents, 40.2% were from high-income countries (HICs), and 59.8% were from low- and middle-income countries (LMICs). Motor vehicle accidents were reported as the leading cause of neurotrauma, followed by workplace injury and assault. Of respondents, 84.1% reported having a helmet law in their country. HICs (4.38 ± 0.78) were ranked more likely than LMICs (2.88 ± 1.34; P = 0.0001) to enforce helmet laws on a scale of 1-10. Effectiveness of helmet laws was rated as 3.94 ± 0.95 out of 10. Measures regarding prehospital care varied between HICs and LMICs. Patients in HICs were more likely to use public emergency ambulance transportation (81.8% vs. 42.9%; P = 0.0004). All prehospital personnel having emergency training was also reported to be more likely in HICs than LMICs (60.6% vs. 8.7%; P = 0.0001)., Conclusions: When injuries occur, timely access to neurosurgical care is critical. A focus on prehospital components of the trauma system is paramount, and policymakers can use the information presented here to implement and refine health care systems to ensure safe, timely, affordable, and equitable access to neurotrauma care., (Published by Elsevier Inc.)

Objective: All-terrain vehicle (ATV) and dirt bike crashes frequently result in traumatic brain injury. The authors performed a retrospective study to evaluate the role of helmets in the neurosurgical outcomes of pediatric patients involved in ATV and dirt bike crashes who were treated at their institution during the last decade., Methods: The authors analyzed data on all pediatric patients involved in ATV or dirt bike crashes who were evaluated at a single regional level I pediatric trauma center between 2010 and 2019. Patients were excluded if the crash occurred in a competition (n = 70) or if helmet status could not be determined (n = 18). Multivariable logistic regression was used to analyze the association of helmet status with the primary outcomes of 1) neurosurgical consultation, 2) intracranial injury (including skull fracture), and 3) moderate or severe traumatic brain injury (MSTBI) and to control for literature-based, potentially confounding variables., Results: In total, 680 patients were included (230 [34%] helmeted patients and 450 [66%] unhelmeted patients). Helmeted patients were more frequently male (81% vs 66%). Drivers were more frequently helmeted (44.3%) than passengers (10.5%, p < 0.001). Head imaging was performed to evaluate 70.9% of unhelmeted patients and 48.3% of helmeted patients (p < 0.001). MSTBI (8.0% vs 1.7%, p = 0.001) and neurosurgical consultation (26.2% vs 9.1%, p < 0.001) were more frequent among unhelmeted patients. Neurosurgical injuries, including intracranial hemorrhage (16% vs 4%, p < 0.001) and skull fracture (18% vs 4%, p < 0.001), were more common in unhelmeted patients. Neurosurgical procedures were required by 2.7% of unhelmeted patients. One helmeted patient (0.4%) required placement of an intracranial pressure monitor, and no other helmeted patients required neurosurgical procedures. After adjustment for age, sex, driver status, vehicle type, and injury mechanism, helmet use significantly reduced the odds of neurosurgical consultation (OR 0.250, 95% CI 0.140-0.447, p < 0.001), intracranial injury (OR 0.172, 95% CI 0.087-0.337, p < 0.001), and MSTBI (OR 0.244, 95% CI 0.079-0.758, p = 0.015). The unadjusted absolute risk reduction provided by helmet use equated to a number-needed-to-helmet of 6 riders to prevent 1 neurosurgical consultation, 4 riders to prevent 1 intracranial injury, and 16 riders to prevent 1 MSTBI., Conclusions: Helmet use remains problematically low among young ATV and dirt bike riders, especially passengers. Expanding helmet use among these children could significantly reduce the rates of intracranial injury and MSTBI, as well as the subsequent need for neurosurgical procedures. Promoting helmet use among recreational ATV and dirt bike riders must remain a priority for neurosurgeons, public health officials, and injury prevention professionals.

Rotational acceleration of the head is a principal cause of concussion and traumatic brain injury. Several rotation-damping systems for helmets have been introduced to better protect the brain from rotational forces. But these systems have not been evaluated in snow sport helmets. This study investigated two snow sport helmets with different rotation-damping systems, termed MIPS and WaveCel, in comparison to a standard snow sport helmet without a rotation-damping system. Impact performance was evaluated by vertical drops of a helmeted Hybrid III head and neck onto an oblique anvil. Six impact conditions were tested, comprising two impact speeds of 4.8 and 6.2 m/s, and three impact locations. Helmet performance was quantified in terms of the linear and rotational kinematics, and the predicted probability of concussion. Both rotation-damping systems significantly reduced rotational acceleration under all six impact conditions compared to the standard helmet, but their effect on linear acceleration was less consistent. The highest probability of concussion for the standard helmet was 89%, while helmets with MIPS and WaveCel systems exhibited a maximal probability of concussion of 67 and 7%, respectively. In conclusion, rotation-damping systems of advanced snow sport helmets can significantly reduce rotational head acceleration and the associated concussion risk., (© 2021. The Author(s).)

New helmet technologies have been developed to improve the mitigation of traumatic brain injury (TBI) in bicycle accidents. However, their effectiveness under oblique impacts, which produce more strains in the brain in comparison with vertical impacts adopted by helmet standards, is still unclear. Here we used a new method to assess the brain injury prevention effects of 27 bicycle helmets in oblique impacts, including helmets fitted with a friction-reducing layer (MIPS), a shearing pad (SPIN), a wavy cellular liner (WaveCel), an airbag helmet (Hövding) and a number of conventional helmets. We tested whether helmets fitted with the new technologies can provide better brain protection than conventional helmets. Each helmeted headform was dropped onto a 45° inclined anvil at 6.3 m/s at three locations, with each impact location producing a dominant head rotation about one anatomical axes of the head. A detailed computational model of TBI was used to determine strain distribution across the brain and in key anatomical regions, the corpus callosum and sulci. Our results show that, in comparison with conventional helmets, the majority of helmets incorporating new technologies significantly reduced peak rotational acceleration and velocity and maximal strain in corpus callosum and sulci. Only one helmet with MIPS significantly increased strain in the corpus collosum. The helmets fitted with MIPS and WaveCel were more effective in reducing strain in impacts producing sagittal rotations and a helmet fitted with SPIN in coronal rotations. The airbag helmet was effective in reducing brain strain in all impacts, however, peak rotational velocity and brain strain heavily depended on the analysis time. These results suggest that incorporating different impact locations in future oblique impact test methods and designing helmet technologies for the mitigation of head rotation in different planes are key to reducing brain injuries in bicycle accidents., (© 2021. The Author(s).)

Previous studies revealed that oxidative stress and inflammation are the main contributors to secondary injury after traumatic brain injury (TBI). In an earlier study, we reported that lutein/zeaxanthin isomers (L/Zi) exert antioxidative and anti-inflammatory effects by activating the nuclear factor-kappa B (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. However, its precise role and underlying mechanisms were largely unknown after TBI. This study was conducted to investigate the potential mechanism of L/Zi isomers in a TBI model induced by a cold injury model in mice. To investigate the effects of L/Zi, male C57BL/6j mice-induced brain injury using the cold trauma model was allocated into two groups (n = 7): (i) TBI + vehicle group and (ii) TBI + L/Zi group (20 mg/kg BW). Brain samples were collected 24 h later for analyses. L/Zi given immediately after the injury decreased infarct volume and blood-brain barrier (BBB) permeability; L/Zi treatment also significantly reduced proinflammatory cytokines, including interleukin1 beta (IL-1β), interleukin 6 (IL-6), and NF-κB levels and increased growth-associated protein 43 (GAP-43), neural cell adhesion molecule (NCAM), brain-derived neurotrophic factor (BDNF), and Nrf2 levels compared with vehicle control. These data suggest that L/Zi improves mitochondrial function in TBI models, possibly decreasing inflammation and activating the Nrf2 pathway., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study aimed to measure the preventive effect of seat belt on traumatic brain injury (TBI) and to compare the effect according to the crash severities and collision directions., Methods: Korea In-Depth Accident Study (KIDAS) has collected vehicle and demographic data on injured occupants involved in motor vehicle collisions (MVCs) who visited three emergency medical centers for calendar years 2011-2016. Primary and secondary end points were TBI (abbreviated injury score 2+) and in-hospital mortality. Crush extent (CE) was classified into 1-2, 3-4, 5-6, and 7-9 according to the crash severity. We calculated adjusted odds ratios (ORs) of seat belts and CE for study outcomes and developed an interaction model in each collision direction using multivariate logistic regression analysis., Results: Of the 2,245 occupants who were injured in MVCs, 295 (13.1%) occupants sustained TBI. In univariate analysis, old age, unbelted status, lateral collision, and higher CE were factors associated with TBI in MVCs. Occupants with belted status was less likely to have TBI and in-hospital mortality compared with those with unbelted status [AORs (95% CI) 0.48 (0.37-0.62) and 0.49 (0.30-0.81), respectively]. In interaction analysis, preventive effects of seat belts on TBI from MVCs were retained within CE 5-6 in frontal MVCs and within CE 1-2 in near side lateral MVCs, and those of seat belts on in-hospital mortality were reserved within CE 3-4 in frontal and rollover MVCs., Conclusions: The preventive effects of seat belts on TBI and in-hospital mortality are preserved within a limited crash severity in each collision direction., (© 2019. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The present study aimed to further explore the potential interaction between oxidative stress and autophagy in the progression of traumatic brain injury (TBI) and therapeutic mechanism of calcitriol, the active form of vitamin D (VitD)., Methods: Neuroprotective effects of calcitriol were examined following TBI. We further evaluated the impacts of TBI and calcitriol treatment on autophagic process and nuclear factor E2-related factor 2 (Nrf2) signaling., Results: We found that treatment of calcitriol markedly ameliorated the neurological deficits and histopathological changes following TBI. The brain damage impaired autophagic flux and impeded Nrf2 signaling, the major regulator in antioxidant response, consequently leading to uncontrolled and excessive oxidative stress. Meanwhile, calcitriol promoted autophagic process and activated Nrf2 signaling as evidenced by the reduced Keap1 expression and enhanced Nrf2 translocation, thereby mitigating TBI-induced oxidative damage. In support, we further found that chloroquine (CQ) treatment abrogated calcitriol-induced autophagy and compromised Nrf2 activation with increased Keap1 accumulation and reduced expression of Nrf2-targeted genes. Additionally, both CQ treatment and Nrf2 genetic knockout abolished the protective effects of calcitriol against both TBI-induced neurological deficits and neuronal apoptosis., Conclusions: Therefore, our work demonstrated a neuroprotective role of calcitriol in TBI by triggering Nrf2 activation, which might be mediated by autophagy., (© 2021. The Author(s).)

Recently, coagulation factor IX and its activation peptide have been reported to suppress the permeability of vascular endothelial cells. In this study, the therapeutic effects of a synthesized activation peptide is investigated in traumatic brain injury model rats. In cerebral contusion, dysfunction of the blood brain barrier with increasing vascular permeability promotes the progression of neuropathy after injury. The model rats were generated by controlled cortical impact. Then, rats were intravenously injected with 350 μg/kg of the synthesized activation peptide or PBS as a control, every day for a month. Behavioral studies were conducted during a month of observation. For morphological analysis, macro- and microscopic observation were performed. Water content of brain tissue was used to assess edema. To assess the function of blood brain barrier, Evans Blue method was employed. In the neurological examinations and beam-walking, the treated rats performed significantly better than control rats. Measurements of cerebral defect volume showed that the treatment significantly reduced it by 82%. Nissl stain showed that neural cells adjacent to impacts were lost in control rats, but saved in treated rats. The treatment significantly reduced brain edema and extravascular leakage of Evans blue. Intravenous injection with a synthesized activation peptide significantly reduced damage to neural tissue and improved neural functioning in the model rats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Recent research suggests that between 20% and 50% of paediatric head injuries attending our emergency department (ED) could be safely discharged soon after triage, without the need for medical review, using a 'Head Injury Discharge At Triage' tool (HIDAT). We sought to implement this into clinical practice., Methods: Paediatric ED triage staff underwent competency-based assessments for HIDAT with all head injury presentations 1 May to 31 October 2020 included in analysis. We determined which patients were discharged using the tool, which underwent CT of the brain and whether there was a clinically important traumatic brain injury or representation to the ED., Results: Of the 1429 patients screened; 610 (43%) screened negative with 250 (18%) discharged by nursing staff. Of the entire cohort, 32 CTs were performed for head injury concerns (6 abnormal) with 1 CT performed in the HIDAT negative group (normal). Of those discharged using HIDAT, four reattended, two with vomiting (no imaging or admission) and two with minor scalp wound infections. Two patients who screened negative declined discharge under the policy with later medical discharge (no imaging or admission). Paediatric ED attendances were 29% lower than in 2018., Conclusion: We have successfully implemented HIDAT into local clinical practice. The number discharged (18%) is lower than originally described; this is likely multifactorial. The relationship between COVID-19 and paediatric ED attendances is unclear but decreased attendances suggest those for whom the tool was originally designed are not attending ED and may be accessing other medical/non-medical resources., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Falls cause approximately 80% of traumatic brain injuries in older adults, and nearly one third of falls by residents in long-term care (LTC) result in head impact. Holding objects during falls, such as mobility aids, may affect the ability of LTC residents to avoid head impact by arresting the fall with their upper limbs. We examined the prevalence of holding objects and their effect on risk for head impact during real-life falls in older adults living in LTC., Methods: We analyzed videos of 1105 real-life falls from standing height by 425 LTC residents, using a validated questionnaire to characterize the occurrence of head impact and whether the resident held objects during descent and impact. We classified objects as either "weight-bearing" (via contact to the fixed environment, eg, chairs and walkers) or "non-weight-bearing" (eg, cups) and tested their effect on odds for head impact with generalized estimating equations., Results: Residents held objects in more than 60% of falls. The odds for head impact were reduced for falls where weight-bearing objects were held or grasped during descent (odds ratio = 0.52; 95% confidence interval = 0.39-0.70) or maintained throughout the fall (odds ratio = 0.34; 95% confidence interval = 0.23-0.49). The most commonly held objects were chairs/wheelchairs (23% of cases), tables/counters (10% of cases), and walkers/rollators (22% of cases); all reduced the odds of head impact when held during descent. Holding non-weight-bearing objects did not affect the odds of head impact (odds ratio = 1.00; 95% confidence interval = 0.64-1.55)., Conclusion: Our results show that older adults in LTC use held, weight-bearing objects to reduce their risk for head impact during falls., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

While sudden loss of perfusion is responsible for ischemia, failure to supply the required amount of oxygen to the tissues is defined as hypoxia. Among several pathological conditions that can impair brain perfusion and oxygenation, cardiocirculatory arrest is characterized by a complete loss of perfusion to the brain, determining a whole brain ischemic-anoxic injury. Differently from other threatening situations of reduced cerebral perfusion, i.e., caused by increased intracranial pressure or circulatory shock, resuscitated patients after a cardiac arrest experience a sudden restoration of cerebral blood flow and are exposed to a massive reperfusion injury, which could significantly alter cellular metabolism. Current evidence suggests that cell populations in the central nervous system might use alternative metabolic pathways to glucose and that neurons may rely on a lactate-centered metabolism. Indeed, lactate does not require adenosine triphosphate (ATP) to be oxidated and it could therefore serve as an alternative substrate in condition of depleted energy reserves, i.e., reperfusion injury, even in presence of adequate tissue oxygen delivery. Lactate enriched solutions were studied in recent years in healthy subjects, acute heart failure, and severe traumatic brain injured patients, showing possible benefits that extend beyond the role as alternative energetic substrates. In this manuscript, we addressed some key aspects of the cellular metabolic derangements occurring after cerebral ischemia-reperfusion injury and examined the possible rationale for the administration of lactate enriched solutions in resuscitated patients after cardiac arrest., Competing Interests: All authors declare not to have any conflict of interest regarding the manuscript.

Aims: Naltrexone is a mu opioid receptor (MOR) antagonist used to treat drug dependence in patients. Previous reports indicated that MOR antagonists reduced neurodegeneration and inflammation after brain injury. The purpose of this study was to evaluate the neuroprotective effect of naltrexone in cell culture and a mouse model of traumatic brain injury (TBI)., Methods: The neuroprotective effect of naltrexone was examined in primary cortical neurons co-cultured with BV2 microglia. Controlled cortical impact (CCI) was delivered to the left cerebral cortex of adult male MOR wild-type (WT) and knockout (KO) mice. Naltrexone was given daily for 4 days, starting from day 2 after lesioning. Locomotor activity was evaluated on day 5 after the CCI. Brain tissues were collected for immunostaining, Western, and qPCR analysis., Results: Glutamate reduced MAP2 immunoreactivity (-ir), while increased IBA1-ir in neuron/BV2 co-culture; both responses were antagonized by naltrexone. TBI significantly reduced locomotor activity and increased the expression of IBA1, iNOS, and CD4 in the lesioned cortex. Naltrexone significantly and equally antagonized the motor deficits and expression of IBA1 and iNOS in WT and KO mice. TBI-mediated CD4 protein production was attenuated by naltrexone in WT mice, but not in KO mice., Conclusion: Naltrexone reduced TBI-mediated neurodegeneration and inflammation in MOR WT and KO mice. The protective effect of naltrexone involves non-MOR and MOR mechanisms., (© 2021 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Objective: Traumatic brain injury (TBI) induced the gastrointestinal inflammation that is associated with TBI-related morbidity and mortality. Carbon monoxide-releasing molecule (CORM)-3 is a water-soluble exogenous carbon monoxide that exerts protective effects against inflammation-induced pyroptosis. We investigated the gastrointestinal inflammation in a rodent model of traumatic brain injury (TBI) with subsequent hemorrhagic shock and resuscitation (HSR), as well as effects of CORM-3 using an intestinal injection on both gut and brain., Methods: Following exposure to TBI plus HSR, rats were administrated with CORM-3 (8 mg/kg) through an intestinal injection after resuscitation immediately. The pathological changes and pyroptosis in the gut were measured at 24 h and 30 day post-trauma. We also assessed the intestinal and cortical CO content, as well as IL-1β and IL-18 levels in the serum within 48 h after trauma. We then explored pathological changes in the ventromedial prefrontal cortex (vmPFC) and neurological behavior deficits on 30 day post-trauma., Results: After TBI + HSR exposure, CORM-3-treated rats presented significantly decreased pyroptosis, more CO content in the jejunum, and lower IL-1β, IL-18 levels in the serum at 24 h after trauma. Moreover, the rats treated with CORM-3 exerted ameliorated jejunal and vmPFC injury, enhanced learning/memory ability and exploratory activity, improved anxiety-like behaviors than the TBI + HSR-treated rats on 30 day post-trauma., Conclusion: These experimental data demonstrated and bidirectional gut-brain interactions after TBI, anti-inflammatory effects of CORM-3, which may improve late outcomes after brain injury., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Sestrin2 (SESN2) is stress-inducible protein that confers cytoprotective effects against various noxious stimuli. Accumulating evidence has documented that SESN2 has potent anti-apoptosis and anti-oxidative stress functions. However, whether it provides neuroprotection in traumatic brain injury (TBI) models remains unexplored. The purpose of this study was to explore the regulatory effect of SESN2 on TBI using in vivo and in vitro models. We found that TBI resulted in a marked induction of SESN2 in the cerebral cortex tissues of mice. SESN2 overexpression in the brain by in vivo gene transfer significantly decreased neurological deficit, brain edema, and neuronal apoptosis of mice with TBI. Moreover, the overexpression of SESN2 significantly decreased the oxidative stress induced by TBI in mice. In vitro studies of TBI demonstrated that SESN2 overexpression decreased apoptosis and oxidative stress in scratch-injured cortical neurons. Notably, SESN2 overexpression increased the nuclear levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and enhanced the activation of Nrf2 antioxidant signaling in in vivo and in vitro models of TBI. In addition, the inhibition of Nrf2 significantly abolished SESN2-mediated neuroprotective effects in vivo and in vitro. In conclusion, these results of our work demonstrate that SESN2 protects against TBI by enhancing the activation of Nrf2 antioxidant signaling.

Background: The aim of this study was to investigate whether AMN082 exerts its neuroprotective effect by attenuating glutamate receptor-associated neuronal apoptosis and improving functional outcomes after traumatic brain injury (TBI)., Methods: Anesthetized male Sprague-Dawley rats were divided into the sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 (10 mg/kg) was intraperitoneally injected 0, 24, or 48 h after TBI. In the 120 min after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. Motor function, the infarct volume, neuronal nitrosative stress-associated apoptosis, and N-methyl-D-aspartate receptor 2A (NR2A) and NR2B expression in the pericontusional cortex were measured on the 3rd day after TBI., Results: The results showed that the AMN082-treated group had a lower ICP and higher CPP after TBI. TBI-induced motor deficits, the increase in infarct volume, neuronal apoptosis, and 3-nitrotyrosine and inducible nitric oxide synthase expression in the pericontusional cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased NR2A and NR2B expression in neuronal cells., Conclusions: We concluded that intraperitoneal injection of AMN082 for 3 days may ameliorate TBI by attenuating glutamate receptor-associated nitrosative stress and neuronal apoptosis in the pericontusional cortex. We suggest that AMN082 administration in the acute stage may be a promising strategy for TBI.

Traumatic brain injury (TBI) remains one of the leading causes of death and disability worldwide; more than 10 million people are hospitalized for TBI every year around the globe. While the primary injury remains unavoidable and not accessible to treatment, the secondary injury which includes oxidative stress, inflammation, excitotoxicity, but also complicating coagulation abnormalities, is potentially avoidable and profoundly affects the therapeutic process and prognosis of TBI patients. The endothelial glycocalyx, the first line of defense against endothelial injury, plays a vital role in maintaining the delicate balance between blood coagulation and anticoagulation. However, this component is highly vulnerable to damage and also difficult to examine. Recent advances in analytical techniques have enabled biochemical, visual, and computational investigation of this vascular component. In this review, we summarize the current knowledge on (i) structure and function of the endothelial glycocalyx, (ii) its potential role in the development of TBI associated coagulopathy, and (iii) the options available at present for detecting and protecting the endothelial glycocalyx.

Secondary injury is the main cause of high mortality and poor prognosis of TBI, which has recently been suggested to be related to ferroptosis. Polydatin, a monocrystalline compound extracted from the rhizome of Polygonum, has been shown to exert potential neuroprotective effects. However, its role and mechanism in the secondary injury of TBI has not been elucidated. In this study, the inhibition of Polydatin on ferroptosis was observed both in the hemoglobin treated Neuro2A cells in vitro and in TBI mouse model in vivo, characterized by reversion of accumulation or deposition of free Fe 2+ , increased content of MDA, decreased activity of key REDOX enzyme GPx4, cell death and tissues loss. Although Polydatin corrected the increased mRNA levels of ferroptosis signaling molecules GPX4, SLC7A11, PTGS2, and ATP5G3 after TBI, TBI and Polydatin treatment had no significant effect on their protein expression. Notably, Polydatin could completely reverse the decrease of GPx4 activity after TBI in vivo and in vitro, and the effect was stronger than that of the classical ferroptosis inhibitor FER-1 in vitro. Further, Polydatin has been shown to reduce the severity of acute neurological impairment and significantly improve subacute motor dysfunction in TBI mice. Our findings provided translational insight into neuroprotection with Polydatin in TBI by inhibiting ferroptosis mainly depending on the maintenance of GPx4 activity., Competing Interests: Declaration of competing interest All authors declared no conflicts of interest in this work., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Special Operations Forces have made brain health a medical priority in recent years, and new guidance identified a new challenge-unconventionally acquired brain injury (UBI). Although this emerging condition is described as a cluster of neurosensory and cognitive symptoms with unknown etiology/ origin, there remain critical questions about how this diagnosis differs from other brain injuries. More importantly, there are limited recommendations about how medical personnel should approach the problem. The current discussion will provide context and information about UBI based on higher guidance and will also review the scant literature to provide context. Foremost, UBI can be distinguished from traumatic brain injury (TBI) largely due to an unknown point of injury. The described symptoms otherwise appear to be largely the same as TBI. Likewise, the recommended course of treatment is to follow the Clinical Practice Guidelines for mild TBI/TBI even if the injury is an actual or suspected UBI. Personnel must be careful to avoid entering sensitive information into the medical record, which may be particularly challenging if identifying the cause involves classified information about an unconventional weapon. Finally, we briefly discuss the literature about several suspected incidents fitting UBI diagnostic criteria, and we conclude with five primary takeaways for medical personnel to follow., (2021.)

Young children have a high risk of sustaining a traumatic brain injury (TBI), which can have debilitating life-long consequences. Importantly, the young brain shows particular vulnerability to injury, likely attributed to ongoing maturation of the myelinating nervous system at the time of insult. Here, we examined the effect of acute treatment with the partial tropomyosin receptor kinase B (TrkB) agonist, LM22A-4, on pathological and neurobehavioral outcomes after pediatric TBI, with the hypothesis that targeting TrkB would minimize tissue damage and support functional recovery. We focused on myelinated tracts-the corpus callosum and external capsules-based on recent evidence that TrkB activation potentiates oligodendrocyte remyelination. Male mice at postnatal day 21 received an experimental TBI or sham surgery. Acutely post-injury, extensive cell death, a robust glial response and disruption of compact myelin were evident in the injured brain. TBI or sham mice then received intranasal saline vehicle or LM22A-4 for 14 days. Behavior testing was performed from 4 weeks post-injury, and brains were collected at 5 weeks for histology. TBI mice showed hyperactivity, reduced anxiety-like behavior, and social memory impairments. LM22A-4 ameliorated the abnormal anxiolytic phenotype but had no effect on social memory deficits. Use of spectral confocal reflectance microscopy detected persistent myelin fragmentation in the external capsule of TBI mice at 5 weeks post-injury, which was accompanied by regionally distinct deficits in oligodendrocyte progenitor cells and post-mitotic oligodendrocytes, as well as chronic reactive gliosis and atrophy of the corpus callosum and injured external capsule. LM22A-4 treatment ameliorated myelin deficits in the perilesional external capsule, as well as tissue volume loss and the extent of reactive gliosis. However, there was no effect of this TrkB agonist on oligodendroglial populations detected at 5 weeks post-injury. Collectively, our results demonstrate that targeting TrkB immediately after TBI during early life confers neuroprotection and preserves myelin integrity, and this was associated with some improved neurobehavioral outcomes as the pediatric injured brain matures., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Mild traumatic brain injury (mTBI), more colloquially known as concussion, is common in contact sports such as American football, leading to increased scrutiny of head protective gear. Standardized laboratory impact testing, such as the yearly National Football League (NFL) helmet test, is used to rank the protective performance of football helmets, motivating new technologies to improve the safety of helmets relative to existing equipment. In this work, we hypothesized that a helmet which transmits a nearly constant minimum force will result in a reduced risk of mTBI. To evaluate the plausibility of this hypothesis, we first show that the optimal force transmitted to the head, in a reduced order model of the brain, is in fact a constant force profile. To simulate the effects of a constant force within a helmet, we conceptualize a fluid-based shock absorber system for use within a football helmet. We integrate this system within a computational helmet model and simulate its performance on the standard NFL helmet test impact conditions. The simulated helmet is compared with other helmet designs with different technologies. Computer simulations of head impacts with liquid shock absorption predict that, at the highest impact speed (9.3 m/s), the average brain tissue strain is reduced by 27.6% ± 9.3 compared to existing helmet padding when tested on the NFL helmet protocol. This simulation-based study puts forth a target benchmark for the future design of physical manifestations of this technology., (Copyright © 2021 by ASME.)

Introduction: Neurotrauma is an important but preventable cause of death and disability worldwide, with the majority being associated with road traffic collisions (RTCs). The greatest burden is seen in low -and middle- income countries (LMICs) where variations in the environment, infrastructure, population and habits can challenge the success of conventional preventative approaches. It is therefore necessary to understand local perspectives to allow for the development and implementation of context-specific strategies which are effective and sustainable., Methods: This study took place in Colombia where qualitative data collection was carried out with ten key informants between October and November 2019. Semi-structured interviews were conducted and explored perceptions on RTCs and neurotrauma, preventative strategies and interventions, and the role of research in prevention. Interview transcripts were analysed by thematic analysis using a framework approach., Results: Participants' confirmed that RTCs are a significant problem in Colombia with neurotrauma as an important outcome. Human and organisational factors were identified as key causes of the high rates of RTCs. Participants described the current local preventative strategies, but were quick to discuss limitations and challenges to their success. Key barriers reported were poor attitudes and knowledge, particularly in the community. Suggestions were provided on ways to improve prevention through better education and awareness, stricter enforcement and new policies on prevention, proper budgeting and resource allocation, as well as through collaboration and changes in attitudes and leadership. Participants identified four key research areas they felt would influence prevention of RTCs and associated neurotrauma: causes of RTCs; consequences and impact of RTCs; public involvement in research; improving prevention., Conclusion: RTCs are a major problem in Colombia despite the current preventative strategies and interventions. Findings from this study have a potential to influence policy, practice and research by illustrating different solutions to the challenges surrounding prevention and by highlighting areas for further research., Competing Interests: The authors have declared that no competing interests exist.

The purpose of this clinical trial was to examine whether internal jugular vein compression (JVC)-using an externally worn neck collar-modulated the relationships between differential head impact exposure levels and pre- to postseason changes in diffusion tensor imaging (DTI)-derived diffusivity and anisotropy metrics of white matter following a season of American tackle football. Male high-school athletes (n = 284) were prospectively assigned to a non-collar group or a collar group. Magnetic resonance imaging data were collected from participants pre- and postseason and head impact exposure was monitored by accelerometers during every practice and game throughout the competitive season. Athletes' accumulated head impact exposure was systematically thresholded based on the frequency of impacts of progressively higher magnitudes (10 g intervals between 20 to 150 g) and modeled with pre- to postseason changes in DTI measures of white matter as a function of JVC neck collar wear. The findings revealed that the JVC neck collar modulated the relationships between greater high-magnitude head impact exposure (110 to 140 g) and longitudinal changes to white matter, with each group showing associations that varied in directionality. Results also revealed that the JVC neck collar group partially preserved longitudinal changes in DTI metrics. Collectively, these data indicate that a JVC neck collar can provide a mechanistic response to the diffusion and anisotropic properties of brain white matter following the highly diverse exposure to repetitive head impacts in American tackle football. Clinicaltrials.gov: NCT# 04068883., (© 2020 Wiley Periodicals LLC.)

Background: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial/macrophage activation and neuroinflammation are key cellular events following TBI, but the regulatory and functional mechanisms are still not well understood. Myeloid-epithelial-reproductive tyrosine kinase (Mer), a member of the Tyro-Axl-Mer (TAM) family of receptor tyrosine kinases, regulates multiple features of microglial/macrophage physiology. However, its function in regulating the innate immune response and microglial/macrophage M1/M2 polarization in TBI has not been addressed. The present study aimed to evaluate the role of Mer in regulating microglial/macrophage M1/M2 polarization and neuroinflammation following TBI., Methods: The controlled cortical impact (CCI) mouse model was employed. Mer siRNA was intracerebroventricularly administered, and recombinant protein S (PS) was intravenously applied for intervention. The neurobehavioral assessments, RT-PCR, Western blot, magnetic-activated cell sorting, immunohistochemistry and confocal microscopy analysis, Nissl and Fluoro-Jade B staining, brain water content measurement, and contusion volume assessment were performed., Results: Mer is upregulated and regulates microglial/macrophage M1/M2 polarization and neuroinflammation in the acute stage of TBI. Mechanistically, Mer activates the signal transducer and activator of transcription 1 (STAT1)/suppressor of cytokine signaling 1/3 (SOCS1/3) pathway. Inhibition of Mer markedly decreases microglial/macrophage M2-like polarization while increases M1-like polarization, which exacerbates the secondary brain damage and sensorimotor deficits after TBI. Recombinant PS exerts beneficial effects in TBI mice through Mer activation., Conclusions: Mer is an important regulator of microglial/macrophage M1/M2 polarization and neuroinflammation, and may be considered as a potential target for therapeutic intervention in TBI.

Introduction: We previously showed that the addition of valproic acid (VPA), a histone deacetylase inhibitor, to fresh frozen plasma (FFP) resuscitation attenuates brain lesion size and swelling following traumatic brain injury (TBI) and hemorrhagic shock (HS). The goal of this study was to use computational biology tools to investigate the effects of FFP+VPA on the brain transcriptome following TBI+HS., Methods: Swine underwent TBI+HS, kept in shock for 2 h, and resuscitated with FFP or FFP + VPA (n = 5/group). After 6 h of observation, brain RNA was isolated and gene expression was analyzed using a microarray. iPathwayGuide, Gene Ontology (GO), Gene-Set Enrichment Analysis, and Enrichment Mapping were used to identify significantly impacted genes and transcriptomic networks., Results: Eight hundred differentially expressed (DE) genes were identified out of a total of 9,118 genes. Upregulated genes were involved in promotion of cell division, proliferation, and survival, while downregulated genes were involved in autophagy, cell motility, neurodegenerative diseases, tumor suppression, and cell cycle arrest. Seven hundred ninety-one GO terms were significantly enriched. A few major transcription factors, such as TP53, NFKB3, and NEUROD1, were responsible for modulating hundreds of other DE genes. Network analysis revealed attenuation of interconnected genes involved in inflammation and tumor suppression, and an upregulation of those involved in cell proliferation and differentiation., Conclusion: Overall, these results suggest that VPA treatment creates an environment that favors production of new neurons, removal of damaged cells, and attenuation of inflammation, which could explain its previously observed neuroprotective effects., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)

Research on the prevention of post-traumatic epilepsy (PTE) has seen remarkable advances regarding its physiopathology in recent years. From the search for biomarkers that might be used to indicate individual susceptibility to the development of new animal models and the investigation of new drugs, a great deal of knowledge has been amassed. Various groups have concentrated efforts in generating new animal models of traumatic brain injury (TBI) in an attempt to provide the means to further produce knowledge on the subject. Here we forward the hypothesis that restricting the search of biomarkers and of new drugs to prevent PTE by using only a limited set of TBI models might hamper the understanding of this relevant and yet not preventable medical condition.

Background and Objective : To simulate infant skull trauma after low height falls when variable degrees of ossification of the sutures are present. Methods : A finite elements model of a four-week-old infant skull was developed for simulating low height impact from 30 cm and 50 cm falls. Two impacts were simulated: An occipito-parietal impact on the lambdoid suture and a lateral impact on the right parietal and six cases were considered: unossified and fully ossified sutures, and sagittal, metopic, right lambdoid and right coronal craniosynostosis. Results : 26 simulations were performed. Results showed a marked increase in strain magnitudes in skulls with unossified sutures and fontanels. Higher deformations and lower Von Mises stress in the brain were found in occipital impacts. Fully ossified skulls showed less overall deformation and lower Von Mises stress in the brain. Results suggest that neonate skull impact when falling backward has a higher probability of resulting in permanent damage. Conclusion : This work shows an initial approximation to the mechanisms underlying TBI in neonates when exposed to low height falls common in household environments, and could be used as a starting point in the design and development of cranial orthoses and protective devices for preventing or mitigating TBI.

Background: Helmets are effective in reducing traumatic brain injury. However, population effects of helmet laws have not been well described. This study assesses the impact of helmet laws on the motorcycle (MC) fatality rate in the United States from 1999 to 2015., Methods: Fatality Analysis Reporting System MC fatalities (aged ≥16 years), crash characteristics, and MC-related laws were collected by year for all 50 states from 1999 to 2015 to create a pooled time series. Generalized linear autoregressive modeling was applied to assess the relative contribution of helmet laws to the MC fatality rate while controlling for other major driver laws and crash characteristics., Results: Universal helmet laws were associated with a 36% to 45% decline in the motorcycle crash mortality rate during the study period across all age cohorts (unstandardized regression coefficients are reported): 16 to 20 years, B = -0.45 (p < 0.05); 21 to 55 years, B = -0.42 (p < 0.001); 56 to 65 years, B = -0.38 (p < 0.04); and older than 65 years, B = -0.36 (p < 0.02). Partial helmet laws were associated with a 1% to 81% increase in the fatality rate compared with states with no helmet laws and a 22% to 45% increase compared with universal laws. Helmet usage did not attenuate the countervailing effect of weaker partial laws for 16 to 20 years (B = 0.01 [p < 0.001]). Other laws associated with a declining motorcycle crash mortality rate included the following: social host/overservice laws, 21 to 55 years (B = -0.38 [p < 0.001]); 56 to 65 years (B = -0.16 [p < 0.002]), and older than 65 years (B = -0.12 [p < 0.003]); laws reducing allowable blood alcohol content, 21 to 55 years (B = -4.9 [p < 0.02]); and laws limiting passengers for new drivers 16 to 20 years (B = -0.06 [p < 0.01])., Conclusion: During the period of the study, universal helmet laws were associated with a declining mortality rate, while partial helmet laws were associated with an increasing mortality rate. Other state driver laws were also associated with a declining rate. In addition to universal helmet laws, advocating for strict alcohol control legislation and reevaluation of licenses in older riders could also result in significant reduction in MC-related mortality., Level of Evidence: Prognostic and epidemiological, level III.

The US Department of Defense (DoD) recognizes the importance of warfighter brain health with the establishment of the Warfighter Brain Health Initiative and Strategy. For a warfighter, also known as a service member, to perform at their highest level, cognitive and physical capabilities must be optimized. This initiative addresses brain health, brain exposures, to include blast overpressure exposures from weapons and munitions, traumatic brain injury (TBI), and long-term or late effects of TBI. The DoD's pursuit of maximal strength hinges on the speed of decisions (neurocognitive) and detection of brain injury when it occurs. The strategy creates a framework for deliberate, prioritized, and rapid development of end-to-end solutions for warfighter brain health. Through this strategy, DoD is addressing the needs of our service members, their families, line leaders/commanders, and their communities at large. The implications of this initiative and strategy are noteworthy for practitioners because the DoD Warfighter Brain Health construct lends itself to nurse practitioner engagement in clinical practice, patient education, policy development, and emerging research.

Traumatic brain injury (TBI), known as intracranial injury, has been a serious threat to human health. Evidence exists indicating that autophagy and inflammatory responses contribute to secondary brain injury after TBI. Notably, receptor-interacting protein kinase 1 (Ripk1) exerts an important role in cell autophagy. Therefore, this study aims to explore the effect of Ripk1 on neuron autophagy and apoptosis in TBI. Initially, blood samples of patients with TBI and healthy persons were collected to detect the expression of Ripk1, nuclear factor-kappa B (NF-κB), and NF-kB inhibitor α (IKBα). Then rat models with TBI were successfully established and, respectively, treated with shRNA targeting Ripk1 (sh-Ripk1), Ripk1 overexpression plasmid (oe-Ripk1), or IKKα inhibitor (BAY 11-7082). Subsequently, reverse transcription quantitative polymerase chain reaction and Western blot analysis were conducted to detect the expression of Ripk1, IKBα, NF-κB signaling pathway-, and apoptosis-related factors. Enzyme-linked immunosorbent assay was used to detect the expression of inflammatory cytokines. Compared with healthy persons, the expression of Ripk1, NF-κB and IKBα in blood of TBI patients was significantly upregulated. After silencing of Ripk1 or inhibition of the NF-κB signaling pathway, the expression of IL-1β, IL-6, TNF-α, Bax, and cleaved-caspase-3 was downregulated, and the expression of Bcl-2, ATG5, and LC3II/LC3I was upregulated. Furthermore, neuron injury and apoptosis were notably reduced and neuron autophagy increased significantly by Ripk1 downregulation or IKKα inhibitor. Ripk1 overexpression contributed to activation of NF-κB signaling pathway, whereby aggravating TBI-induced damage. Silencing Ripk1 suppresses TBI by inhibiting inflammation and promoting autophagy of neurons via inhibition of NF-κB signaling pathway.

Ethnopharmacological Relevance: Xuefu Zhuyu decoction (XFZYD) is a traditional Chinese herbal prescription. It is effective in treating traumatic brain injury (TBI). However, the underlying molecular mechanisms remain unclear., Aim of the Study: This study aimed to reveal the possible mechanisms of XFZYD in treating acute TBI through proteomics clues., Materials and Methods: Controlled Cortical Impact (CCI) rats were given gavage administration of XFZYD (9 g/kg/d) or distilled water (equal volume) for three days. The Modified Neurological Severity Score (mNSS), brain water content, HE staining, Nissl staining and immunohistochemistry were performed to assess the effects of XFZYD for TBI treatment. Additionally, tandem mass tag-based (TMT) quantitative proteomics technology was applied to detect proteins of brain cortex. Bioinformatics analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Protein-protein interaction (PPI) networks were used to analyze differentially expressed proteins (DEPs). Bioinformatics Analysis Tool for Molecular mechanism of TCM (BATMAN-TCM) was conducted to anchor diseases and pathways. Besides, western blotting and immunofluorescence were exerted to verify related proteins., Results: XFZYD improved neurologic functions, reduced encephaledema and ameliorated cell morphology around the injured area in CCI rats. A total of 6099 proteins were identified with false discovery rate (FDR) < 1%. Overlapping DEPs (105 DEPs) were identified (295 DEPs and 804 DEPs in CCI/Sham or XFZYD/CCI group, respectively). Of these DEPs, 17 were regulated by XFZYD. Bioinformatics analysis showed that the 17 DEPs were predominantly related to platelet activation and PI3K-Akt signaling pathway. Next, PLG and CD34 were verified with molecular biotechnology., Conclusions: XFZYD exerts therapeutic effects through multi-pathways regulation in the treatment of TBI. This work may provide proteomics clues for the continuation of research on TBI treatment with XFZYD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The homeostasis of the neurovascular unit (NVU) is disrupted after traumatic brain injury (TBI), and therapeutic strategies targeting the NVU would likely improve neurological outcomes after TBI. Sonic Hedgehog (Shh), which is an endogenous activator of the Hedgehog pathway, promotes brain repair in various injuries. In this study, the controlled cortical impact (CCI) was used to establish a moderate TBI model in adult male Sprague-Dawley rats (250-300 g), and the NVU was reconstructed in vitro from the blood-brain barrier (BBB) and neurons to investigate the effects of exogenous Shh protein on TBI. The modified neurological severity scores (mNSS) and Morris water maze tests were used to evaluate the effect of Shh on neurological function after TBI. The effect of Shh on the NVU in vivo was evaluated by detecting the degrees of cerebral edema and neuronal apoptosis. The integrity and permeability of the BBB, the level of inflammatory factors, and the expression of apoptotic proteins were detected to explore the effect of exogenous Shh on the NVU in vitro. The results showed that exogenous Shh reduced cerebral edema and neuronal apoptosis and promoted neurological recovery after TBI in rats. In vitro experiments showed that Shh-induced activation of the Hedgehog pathway promoted stability of the NVU by reducing damage to the tight junction structure and inhibiting the release of inflammatory factors and neuron apoptosis. Based on these results, the Shh-induced activation of the Hedgehog pathway might be a new promising treatment for TBI.

Traumatic brain injury (TBI) causes substantial mortality and long-term disability worldwide. TGFβ1 is a unique molecular and functional signature in microglia, but the role of TGFβ1 in TBI is not clear. The purpose of this study was to investigate the role of TGFβ1 in TBI. The weight dropping device was used to establish TBI model of rats. Hematoxylin eosin staining and Bielschowsky silver staining were used to assess tissue loss. Beam walking and muscle strength tests were used to assess neurological deficits. Immunohistochemical staining was used to assess axonal injures. Western blotting was used to detect expression of related proteins. RT-PCR was used to detect expression of cytokines. Immunofluorescence staining was used to assess the microglia/macrophages activation. We observed obvious axonal injury and microglia/macrophages activation in the peri-lesion cortex. The expression of inflammatory cytokines was markedly high after TBI. The expression of TGFβ1 and TGFβRI were significantly reduced after TBI. TGFβ1 promoted the functional recovery and alleviated axonal injury 1 day after TBI. TGFβ1 promoted microglia/macrophages polarizing to alternative activation and alleviated neuroinflammation. These effects of TGFβ1 could be inhibited by LY2109761, the inhibitor of TGFRI/II. These results suggested that TGFβ1 played a protective role in axonal injury and could be a potential therapeutic target in early stages following TBI., Competing Interests: Declaration of competing interest All authors declare no conflict of interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Docosahexaenoic acid (DHA) is verified to have neuroprotective effects on traumatic brain injury (TBI) rats by activating Nrf2 signaling pathway, but the role of NOX 2 in this effect has not been illuminated. So this study explored the role of NOX 2 in TBI models treated with DHA, aiming to complete the mechanism of DHA. TBI rat models were constructed with or without DHA treatment, and H 2 O 2 -induced hippocampal neurons were pretreated with DHA alone or in combination with Nrf2 inhibitor brusatol. The neurological function, cognitive ability, and cerebral edema degree of rats were assessed. The apoptosis rate and viability of cells was measured. The generation of NOX 2 , Nrf2, HO-1 and NQO-1 expression levels, and ROS content in hippocampal CA1 region and hippocampal neurons were detected. DHA could not only improve the neurological function, brain edema and cognitive ability in TBI rats, but also decrease effectively the contents of NOX 2 and ROS in hippocampal CA1 region and hippocampal neurons. DHA promoted the nuclear transposition of Nrf2 and the expression levels of HO-1 and NQO-1 in hippocampal CA1 region and hippocampal neurons. On the contrary, Nrf2 inhibitor brusatol inhibited the nuclear transposition of Nrf2 and the expression levels of HO-1 and NQO-1 in hippocampal neurons, promoted the generation of ROS and NOX 2 , and accelerated cell apoptosis. Both in vivo and in vitro experiments demonstrated that DHA treated TBI by reducing NOX 2 generation that might function on Nrf2 signaling pathway, providing a potential evidence for its clinical application.

The use of helmets in equestrian sports has reduced the occurrence of traumatic brain injuries although, despite improvements to helmets, concussion remains a common injury. Currently, equestrian helmets are designed to pass certification standards involving a linear drop test to a rigid surface, while most concussions in equestrian sports result from oblique impacts to a compliant surface. The purpose of this study was to: (1) Compare the head kinematics and brain tissue response of the current equestrian helmet standard (EN1) and proposed standard EN13087-11 (EN2) to those associated with reconstructions of real-world equestrian concussion accidents. (2) Design a test protocol that would reflect the real-world conditions associated with concussion in equestrian sports. (3) To assess the protective capacity of an equestrian helmet using the flat turf and 45° turf proposed test protocols. Results for reconstructions of real-world concussions were obtained from a previous study (Clark et al. in J. Sci. Med. Sport 23:222-236, 2020). Using one jockey helmet model, impact tests were conducted according to the EN1 and EN2 protocols. Additionally, helmeted and unhelmeted tests were conducted at 5.9 and 6.0 m/s on to flat turf and 45° turf anvils for front, front-boss and rear-boss impact locations. The results demonstrated EN1 and EN2 both had higher magnitude accelerations and shorter duration impacts than reconstructed real-world concussive impacts. Impacts to turf anvils, on the other hand, produced similar head kinematics compared to the reconstructed real-world concussive impacts. Additionally, this study demonstrated that helmeted impacts significantly decreased rotational kinematics and brain tissue response below what is associated with unhelmeted impacts for oblique falls. However, the head kinematics and brain tissue response associated with these helmeted falls were consistent with concussion, suggesting that scope exists to improve the capacity of equestrian helmets to protect against concussion.