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Introduction: Cycling is associated with a greater risk of traumatic brain injury (TBI) than other recreational activities. This study aimed to investigate the epidemiology of sports-related TBI in Hong Kong and to examine predictors for recreational cycling-induced intracranial haemorrhage., Methods: This retrospective multicentre study included patients diagnosed with sports-related TBI in public hospitals in Hong Kong from 2015 to 2019. Computed tomography scans were reviewed by an independent assessor. The primary endpoint was traumatic intracranial haemorrhage. The secondary endpoint was an unfavourable Glasgow Outcome Scale (GOS) score at discharge from hospital., Results: In total, 720 patients were hospitalised with sports-related TBI. The most common sport was cycling (59.2%). The crude incidence of cycling-related TBI was 1.1 per 100 000 population. Cyclists were more likely to exhibit intracranial haemorrhage and an unfavourable GOS score, compared with patients who had TBI because of other sports. Although 47% of cyclists had intracranial haemorrhage, only 15% wore a helmet. In multivariate analysis, significant predictors for intracranial haemorrhage were age ≥60 years, antiplatelet medication, moderate or severe TBI, and skull fracture. Among 426 cyclists, 375 (88%) had mild TBI, and helmet wearing was protective against intracranial haemorrhage, regardless of age, antiplatelet medication intake, and mechanism of injury. Of 426 cyclists, 31 (7.3%) had unfavourable outcomes on discharge from hospital., Conclusions: The incidence of sports-related TBI is low in Hong Kong. Although cycling-related head injuries carried greater risks of intracranial haemorrhage and unfavourable outcomes compared with other sports, most cyclists experienced good recovery. Helmet wearing among recreational cyclists with mild TBI was protective against intracranial haemorrhage and skull fracture., Competing Interests: All authors have disclosed no conflicts of interest.

Study Objective: Infants with head trauma often have subtle findings suggestive of traumatic brain injury. Prediction rules for traumatic brain injury among children with minor head trauma have not been specifically evaluated in infants younger than 3 months old. We aimed to determine the risk of clinically important traumatic brain injuries, traumatic brain injuries on computed tomography (CT) images, and skull fractures in infants younger than 3 months of age who did and did not meet the age-specific Pediatric Emergency Care Applied Research Network (PECARN) low-risk criteria for children with minor blunt head trauma., Methods: We conducted a secondary analysis of infants <3 months old in the public use data set from PECARN's prospective observational study of children with minor blunt head trauma. Main outcomes included (1) clinically important traumatic brain injury, (2) traumatic brain injury on CT, and (3) skull fracture on CT., Results: Of 10,904 patients <2 years old, 1,081 (9.9%) with complete data were <3 months old; most (750/1081, 69.6%) sustained falls, and 633/1081 (58.6%) underwent CT scans. Of the 514/1081 (47.5%) infants who met the PECARN low-risk criteria, 1/514 (0.2%, 95% confidence interval [CI] 0.005% to 1.1%), 10/197 (5.1%, 2.5% to 9.1%), and 9/197 (4.6%, 2.1% to 8.5%) had clinically important traumatic brain injuries, traumatic brain injuries on CT, and skull fractures, respectively. Of 567 infants who did not meet the low-risk PECARN criteria, 24/567 (4.2%, 95% CI 2.7% to 6.2%), 94/436 (21.3%, 95% CI 17.6% to 25.5%), and 122/436 (28.0%, 95% CI 23.8% to 32.5%) had clinically important traumatic brain injuries, traumatic brain injuries, and skull fractures, respectively., Conclusion: The PECARN traumatic brain injury low-risk criteria accurately identified infants <3 months old at low risk of clinically important traumatic brain injuries. However, infants at low risk for clinically important traumatic brain injuries remained at risk for traumatic brain injuries on CT, suggesting the need for a cautious approach in these infants., (Copyright © 2021 American College of Emergency Physicians. Published by 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.)

Females have been understudied in pre-clinical and clinical traumatic brain injury (TBI), despite distinct biology and worse clinical outcomes versus males. Sulfonylurea receptor 1 (SUR1) inhibition has shown promising results in predominantly male TBI. A phase II trial is ongoing. We investigated whether SUR1 inhibition effects on contusional TBI differ by sex given that this may inform clinical trial design and/or interpretation. We studied the moderating effects of sex on post-injury brain tissue loss in 142 male and female ATP-binding cassette transporter subfamily C member 8 ( Abcc8 ) wild-type, heterozygote, and knockout mice (12-15 weeks). Monkey fibroblast-like cells and mouse brain endothelium-derived cells were used for in vitro studies. Mice were injured with controlled cortical impact and euthanized 21 days post-injury to assess contusion, brain, and hemisphere volumes (vs. genotype- and sex-matched naïves). Abcc8 knockout mice had smaller contusion volumes ( p  = 0.012) and larger normalized contralateral (right) hemisphere volumes (nRHV; p  = 0.03) after injury versus wild type. This was moderated by sex: Contusions were smaller ( p  = 0.020), nRHV was higher ( p  = 0.001), and there was less global atrophy ( p  = 0.003) in male, but not female, knockout versus wild-type mice after TBI. Less atrophy occurred in males for each copy of Abcc8 lost ( p  = 0.023-0.002, all outcomes). In vitro , sex-determining region Y (SRY) stimulated Abcc8 promoter activity and increased Abcc8 expression. Loss of Abcc8 strongly protected against post-traumatic cerebral atrophy in male, but not female, mice. This may partly be mediated by SRY on the Y-chromosome. Sex differences may have important implications for ongoing and future trials of SUR1 blockade.

Traumatic brain injury (TBI) is a major public health challenge that is also the third leading cause of death worldwide. It is also the leading cause of long-term disability in children and young adults worldwide. Despite a large body of research using predominantly in vivo and in vitro rodent models of brain injury, there is no medication that can reduce brain damage or promote brain repair mainly due to our lack of understanding in the mechanisms and pathophysiology of the TBI. The aim of this review is to examine in vitro TBI studies conducted from 2008-2018 to better understand the TBI in vitro model available in the literature. Specifically, our focus was to perform a detailed analysis of the in vitro experimental protocols used and their subsequent biological findings. Our review showed that the uniaxial stretch is the most frequently used way of load application, accounting for more than two-thirds of the studies reviewed. The rate and magnitude of the loading were varied significantly from study to study but can generally be categorized into mild, moderate, and severe injuries. The in vitro studies reviewed here examined key processes in TBI pathophysiology such as membrane disruptions leading to ionic dysregulation, inflammation, and the subsequent damages to the microtubules and axons, as well as cell death. Overall, the studies examined in this review contributed to the betterment of our understanding of TBI as a disease process. Yet, our review also revealed the areas where more work needs to be done such as: 1) diversification of load application methods that will include complex loading that mimics in vivo head impacts; 2) more widespread use of human brain cells, especially patient-matched human cells in the experimental set-up; and 3) need for building a more high-throughput system to be able to discover effective therapeutic targets for TBI.

This study aimed to assess the neuro-regenerative properties of co-ultramicronized PEALut (Glialia ® ), composed of palmitoylethanolamide (PEA) and the flavonoid luteolin (Lut), in an in vivo model of traumatic brain injury (TBI) and patients affected by moderate TBI. An increase in neurogenesis was seen in the mice at 72 h and 7 d after TBI. The co-ultra PEALut treatment helped the neuronal reconstitution process to restore the basal level of both novel and mature neurons; moreover, it induced a significant upregulation of the neurotrophic factors, which ultimately led to progress in terms of memory recall during behavioral testing. Moreover, our preliminary findings in a clinical trial suggested that Glialia ® treatment facilitated neural recovery on working memory. Thus, co-ultra PEALut (Glialia ® ) could represent a valuable therapeutic agent for intensifying the endogenous repair response in order to better treat TBI.

The interaction of explosion-induced blast waves with the head (i.e., a direct mechanism) or with the torso (i.e., an indirect mechanism) presumably causes traumatic brain injury. However, the understanding of the potential role of each mechanism in causing this injury is still limited. To address this knowledge gap, we characterized the changes in the brain tissue of rats resulting from the direct and indirect mechanisms at 24 h following blast exposure. To this end, we conducted separate blast-wave exposures on rats in a shock tube at an incident overpressure of 130 kPa, while using whole-body, head-only, and torso-only configurations to delineate each mechanism. Then, we performed histopathological (silver staining) and immunohistochemical (GFAP, Iba-1, and NeuN staining) analyses to evaluate brain-tissue changes resulting from each mechanism. Compared to controls, our results showed no significant changes in torso-only-exposed rats. In contrast, we observed significant changes in whole-body-exposed (GFAP and silver staining) and head-only-exposed rats (silver staining). In addition, our analyses showed that a head-only exposure causes changes similar to those observed for a whole-body exposure, provided the exposure conditions are similar. In conclusion, our results suggest that the direct mechanism is the major contributor to blast-induced changes in brain tissues., (© 2021. The Author(s).)

Background: Increased traumatic brain injury (TBI) risk was found in patients with bipolar disorder (BPD). Whether the medications for BPD and dosage moderate the risk of TBI is not clear., Aim: This study aimed to determine whether an association exists between BPD and TBI and whether the prescription of psychotropics moderates TBI risk., Methods: A total of 5606 individuals who had received diagnoses of BPD between January 1, 1997 and December 31, 2013 and 56,060 matched controls without BPD were identified from Taiwan's National Health Insurance Research Database. Cases and controls were followed until the date of TBI diagnosis., Results: BPD was associated with a high risk of TBI (adjusted hazard ratio (aHR): 1.85; 95% CI: 1.62-2.11). Patients with BPD, with or without a history of psychiatric hospitalization, had increased risks of TBI (aHR: 1.94, 95% CI: 1.57-2.4 and aHR: 1.82, 95% CI: 1.55-2.1, respectively). The prescription of typical antipsychotics (0 < defined daily dose (DDD) < 28: hazard ratio (HR) = 1.52, 95% CI: 1.19-1.94; ⩾28 DDD: HR = 1.54, 95% CI: 1.15-2.06) and tricyclic antidepressants (TCAs) (0 < DDD < 28: HR = 1.73, 95% CI: 1.26-2.39; ⩾28 DDD: HR = 1.52, 95% CI: 1.02-2.25) was associated with higher TBI risk. Patients receiving higher doses of benzodiazepines (BZDs) (cumulative dose ⩾28 DDD) had a higher TBI risk (HR = 1.53, 95% CI: 1.13-2.06)., Conclusion: Patients with BPD have a higher risk of TBI. The use of typical antipsychotics, TCAs, or high-dose BZDs increases the risk of TBI in BPD.

Abstract: Traumatic brain injury (TBI) is associated with increased morbidity and mortality in civilian trauma and battlefield settings. It has been classified across a continuum of dysfunctions, with as much as 80% to 90% of cases diagnosed as mild to moderate in combat casualties. In this report, a framework is presented that focuses on the potential benefits for acute noninvasive treatment of reduced cerebral perfusion associated with mild TBI by harnessing the natural transfer of negative intrathoracic pressure during inspiration. This process is known as intrathoracic pressure regulation (IPR) therapy, which can be applied by having a patient breath against a small inspiratory resistance created by an impedance threshold device. Intrathoracic pressure regulation therapy leverages two fundamental principles for improving blood flow to the brain: (1) greater negative intrathoracic pressure enhances venous return, cardiac output, and arterial blood pressure; and (2) lowering of intracranial pressure provides less resistance to cerebral blood flow. These two effects work together to produce a greater pressure gradient that results in an improvement in cerebral perfusion pressure. In this way, IPR therapy has the potential to counter hypotension and hypoxia, potentially significant contributing factors to secondary brain injury, particularly in conditions of multiple injuries that include severe hemorrhage. By implementing IPR therapy in patients with mild-to-moderate TBI, a potential exists to provide early neuroprotection at the point of injury and a bridge to more definitive care, particularly in settings of prolonged delays in evacuation such as those anticipated in future multidomain operations., Level of Evidence: Report., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: There is limited research from Australasian EDs describing the demographic make-up, injury severity and impact of alcohol in patients requiring computed tomography (CT) for suspected traumatic brain injury (TBI). The present study aims to review the frequency and presenting patterns of patients who consume alcohol prior to presenting with suspected TBI., Methods: Retrospective observational study of patients referred for head CT to exclude TBI from a major referral centre and regional ED in New Zealand, between 1 September 2018 and 31 August 2019. Comparison groups were defined as 'alcohol involved' or 'no alcohol involved'., Results: 97/425 (22.8% [95% CI 18.3-27.4]) of included TBI presentations involved alcohol. 73/97 (75.3% [95% CI 58.6-93.5]) were male and 41/97 (42.3% [95% CI 29.3-55.2]) were aged 18-30 years. The alcohol group were more likely to report assault as the injury mechanism (19.6% [95% CI 10.8-28.4] vs 5.2% [95% CI 2.7-7.7], P < 0.05) and have Glasgow Coma Scale scores reflecting more moderate (13.5% [95% CI 5.9-21.1] vs 3.5% [95% CI 1.5-5.6]) and severe (5.6% [95% CI 0.7-10.5] vs 3.2% [95% CI 1.2-5.2] TBI. Presentation times post-injury were delayed compared to the no alcohol group (3.4 h [interquartile range 1.9-14.8] vs 2.8 h [interquartile range 1.8-6.6], P < 0.05)., Conclusion: One quarter of patients with suspected TBI had consumed alcohol prior to their injury. Predominantly, those affected were young males who reported higher rates of assault; however, alcohol use was recorded in all age groups and sex. Alcohol-affected patients presented later, potentially delaying time to diagnosis. The present study supports the call for public health interventions that aim to reduce alcohol misuse., (© 2021 Australasian College for Emergency Medicine.)

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.

Background: The COVID-19 pandemic has led to severe containment measures to protect the population in France. The first lockdown modified daily living and could have led to a decrease in the frequency of severe traumatic brain injury (TBI). In the present study, we compared the frequency and severity of severe TBI before and during the first containment in Normandy., Methods: We included all patients admitted in the intensive care unit (ICU) for severe TBI in the two tertiary neurosurgical trauma centres of Normandy during the first lockdown. The year before the containment served as control. The primary outcome was the number of patients admitted per week in ICU. We compared the demographic characteristics, TBI mechanisms, CT scan, surgical procedure, and mortality rate., Results: The incidence of admissions for severe TBI in Normandy decreased by 33% during the containment. The aetiology of TBI significantly changed during the containment: there were less traffic road accidents and more TBI related to alcohol consumption. Patients with severe TBI during the containment had a better prognosis according to the impact score (p=0.04). We observed a significant decrease in the rate of short-term mortality related to severe TBI during the period of lockdown (p=0.02)., Conclusions: Containment related to the COVID-19 pandemic has resulted in a modification of the mechanisms of severe TBI in Normandy, which was associated with a decline in the rate of short-term death in intensive unit care.

Cytokines are important neuroinflammatory modulators in neurodegenerative brain disorders including traumatic brain injury (TBI) and stroke. However, their temporal effects on the physiological properties of microglia and neurons during the recovery period have been unclear. Here, using an ATP-induced cortical injury model, we characterized selective effects of ATP injection compared to needle-control. In the damaged region, the fluorescent intensity of CX 3 CR1-GFP (+) cells, as well as the cell density, was increased and the maturation of newborn BrdU (+) cells continued until 28 day-post-injection (dpi) of ATP. The excitability and synaptic E/I balance of neurons and the inward and outward membrane currents of microglia were increased at 3 dpi, when expressions of tumor necrosis factor (TNF)-α/interleukin (IL)-1β and IL-10/IL-4 were also enhanced. These changes of both cells at 3 dpi were mostly decayed at 7 dpi and were suppressed by any of IL-10, IL-4, suramin (P2 receptor inhibitor) and 4-AP (K + channel blocker). Acute ATP application alone induced only small effects from both naïve neurons and microglial cells in brain slice. However, TNF-α alone effectively increased the excitability of naïve neurons, which was blocked by suramin or 4-AP. TNF-α and IL-1β increased and decreased membrane currents of naïve microglia, respectively. Our results suggest that ATP and TNF-α dominantly induce the physiological activities of 3 dpi neurons and microglia, and IL-10 effectively suppresses such changes of both activated cells in K + channel- and P2 receptor-dependent manner, while IL-4 suppresses neurons preferentially.

Neurovascular injury is often observed in traumatic brain injury (TBI). However, the relationship between mechanical forces and vascular injury is still unclear. A key question is whether the complex anatomy of vasculature plays a role in increasing forces in cerebral vessels and producing damage. We developed a high-fidelity multiscale finite element model of the rat brain featuring a detailed definition of the angioarchitecture. Controlled cortical impacts were performed experimentally and in-silico. The model was able to predict the pattern of blood-brain barrier damage. We found strong correlation between the area of fibrinogen extravasation and the brain area where axial strain in vessels exceeds 0.14. Our results showed that adjacent vessels can sustain profoundly different axial stresses depending on their alignment with the principal direction of stress in parenchyma, with a better alignment leading to larger stresses in vessels. We also found a strong correlation between axial stress in vessels and the shearing component of the stress wave in parenchyma. Our multiscale computational approach explains the unrecognised role of the vascular anatomy and shear stresses in producing distinct distribution of large forces in vasculature. This new understanding can contribute to improving TBI diagnosis and prevention.

Traumatic brain injuries (TBI) of varied types are common across all populations and can cause visual problems. For military personnel in combat settings, injuries from blast exposures (bTBI) are prevalent and arise from a myriad of different situations. To model these diverse conditions, we are one of several groups modeling bTBI using mice in varying ways. Here, we report a refined analysis of retinal ganglion cell (RGC) damage in male C57BL/6J mice exposed to a blast-wave in an enclosed chamber. Ganglion cell layer thickness, RGC density (BRN3A and RBPMS immunoreactivity), cellular density of ganglion cell layer (hematoxylin and eosin staining), and axon numbers (paraphenylenediamine staining) were quantified at timepoints ranging from 1 to 17-weeks. RNA sequencing was performed at 1-week and 5-weeks post-injury. Earliest indices of damage, evident by 1-week post-injury, are a loss of RGC marker expression, damage to RGC axons, and increase in glial markers expression. Blast exposure caused a loss of RGC somas and axons-with greatest loss occurring by 5-weeks post-injury. While indices of glial involvement are prominent early, they quickly subside as RGCs are lost. The finding that axonopathy precedes soma loss resembles pathology observed in mouse models of glaucoma, suggesting similar mechanisms.

Background: Recommendations for a head computed tomography (CT) scan in elderly patients without a loss of consciousness after a traumatic brain injury and without neurological findings on admission and who are not taking oral anticoagulant therapy, are discordant., Objectives: To determine variables associated with intracranial hemorrhage (ICH) and the need for neurosurgery in elderly patients after low velocity head trauma., Methods: In a regional hospital, we retrospectively selected 206 consecutive patients aged ≥ 65 years with head CT scans ordered in the emergency department because of low velocity head trauma. Outcome variables were an ICH and neurological surgery. Independent variables included age, sex, disability, neurological findings, facial fractures, mental status, headache, head sutures, loss of consciousness, and anticoagulation therapy., Results: Fourteen patients presented with ICH (6.8%, 3.8-11.1%) and three (1.5%, 0.3-4.2%) with a neurosurgical procedure. One patient with a coma (0.5, 0.0-2.7) died 2 hours after presentation. All patients who required surgery or died had neurological findings. Reducing head CT scans by 97.1% (93.8-98.9%) would not have missed any patient with possible surgical utility. Twelve of the 14 patients (85.7%) with an ICH had neurological findings, post-trauma loss of consciousness or a facial fracture were not present in 83.5% (95% confidence interval 77.7-88.3) of the cohort., Conclusions: None of our patients with neurological findings required neurosurgery. Careful palpation of the facial bones to identify facial fractures might aid in the decision whether to perform a head CT scan.

Background: Traumatic brain injury (TBI) is the leading cause of death and disability in young children; however, the impact of mechanism on outcomes has not been fully evaluated. We hypothesized that children with TBI due to abuse would have a higher mortality than children with accidental TBI due to motor vehicle collisions (MVC)., Methods: We performed a retrospective review of the National Kids' Inpatient (KID) hospitalizations database of children <2 years old with TBI due to abuse or MVC (2000-2016). The primary outcome was mortality. Secondary outcomes were length of stay (LOS) and hospital charges. We investigated predictors of mortality with multivariable regression., Results: Of 10,965 children with TBI, 65.2% were due to abuse. Overall mortality was 9.8% (n = 1074). Abused children had longer LOS (5.7 vs 1.6 days, p < 0.0001) and higher hospital charges ($34,314 vs $19,360, p < 0.0001) than children with TBI due to MVC. The odds of mortality were 42% higher in children with abusive head trauma (OR 1.42, 95% CI 1.10-1.83, p = 0.007) compared to MVCs after adjusting for age, race, sex, neurosurgical intervention, injury severity, and insurance., Conclusion: Children with abusive traumatic brain injury have increased risk of mortality, longer LOS, and higher hospital charges compared to children with TBI due to motor vehicle collision after adjusting for relevant confounders. Resources must be directed at prevention and early identification of abuse., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

Unilateral-onset spike-wave discharges (SWDs) following fluid percussion injury (FPI) in rats have been used for nearly two decades as a model for complex partial seizures in human posttraumatic epilepsy (PTE). This study determined if SWDs with a unilateral versus bilateral cortical onset differed. In this experiment, 2-mo-old rats received severe FPI (3 atm) or sham surgery and were instrumented for chronic video-electrocorticography (ECoG) recording (up to 9 mo). The antiseizure drug, carbamazepine (CBZ), and the antiabsence drug, ethosuximide (ETX), were administered separately to determine if they selectively suppressed unilateral- versus bilateral-onset SWDs, respectively. SWDs did not significantly differ between FPI and sham rats on any measured parameter (wave-shape, frequency spectrum, duration, or age-related progression), including unilateral (∼17%) versus bilateral (∼83%) onsets. SWDs with a unilateral onset preferentially originated ipsilateral to the craniotomy in both FPI and sham rats, suggesting that the unilateral-onset SWDs were related to surgical injury and not specifically to FPI. ETX profoundly suppressed SWDs with either unilateral or bilateral onsets, and CBZ had no effect on either type of SWD. These results suggest that SWDs with either a unilateral or bilateral onset have a pharmacosensitivity similar to absence seizures and are very different from the complex partial seizures of PTE. Therefore, SWDs with a unilateral onset after FPI are not a model of the complex partial seizures that occur in PTE, and their use for finding new treatments for PTE could be counterproductive, particularly if their close similarity to normal brain oscillations is not acknowledged. NEW & NOTEWORTHY Unilateral-onset spike-wave discharges (SWDs) in rats have been used to model complex partial seizures in human posttraumatic epilepsy (PTE), compared to bilateral-onset SWDs thought to reflect human absence seizures. Here, we show that both unilateral- and bilateral-onset SWDs following traumatic brain injury are suppressed by the antiabsence drug ethosuximide and are unaffected by the antiseizure drug carbamazepine. We propose that unilateral-onset SWDs are not useful for studying mechanisms of, or treatments for, PTE.

Purpose: In February 2020, the federal state of Tyrol in Austria has become one of the epicenters of the COVID-19 pandemic. Tyrol is known for numerous skiing areas. Thus, winter sport resorts became a starting point for COVID-19 infections spreading towards the rest of the state, Austria and other countries, leading to a mandatory quarantine for almost a million people, who were placed under a curfew and restrictions in daily life. Additionally, all ski resorts and hotels were closed. We aimed to analyze the influence of the COVID-19 quarantine on traumatic brain injury (TBI) cases in Tyrol., Methods: We retrospectively compared demographical and injury characteristics from all TBI patients within the 2020 strict quarantine period with the respective time periods from 2016 to 2019. As our department is the only neurosurgical unit in Tyrol, all patients with moderate or severe TBI are transferred to our hospital., Results: During 3 weeks of the full quarantine period, the weekly TBI cases load decreased significantly in comparison to the same time periods in the years 2016-2019. Furthermore, concomitant skull fractures decreased significantly (p < 0.016), probably reflecting different causative mechanisms. The other demographical and injury characteristics and particularly falls at home stayed relatively unchanged., Conclusion: TBI remained an important contributor to the neurosurgical workflow during the COVID-19 pandemic. Strategies to ensure neurosurgical care also under pandemic-induced lockdown are important.

Purpose: The purpose of this study was to examine the influence of genetic background on the retinal ganglion cell (RGC) response to blast-mediated traumatic brain injury (TBI) in Jackson Diversity Outbred (J:DO), C57BL/6J and BALB/cByJ mice., Methods: Mice were subject to one blast injury of 137 kPa. RGC structure was analyzed by optical coherence tomography (OCT), function by the pattern electroretinogram (PERG), and histologically using BRN3A antibody staining., Results: Comparison of the change in each group from baseline for OCT and PERG was performed. There was a significant difference in the J:DOΔOCT compared to C57BL/6J mice (P = 0.004), but not compared to BALB/cByJ (P = 0.21). There was a significant difference in the variance of the ΔOCT in J:DO compared to both C57BL/6J and BALB/cByJ mice. The baseline PERG amplitude was 20.33 ± 9.32 µV, which decreased an average of -4.14 ± 12.46 µV following TBI. Baseline RGC complex + RNFL thickness was 70.92 ± 4.52 µm, which decreased an average of -1.43 ± 2.88 µm following blast exposure. There was not a significant difference in the ΔPERG between J:DO and C57BL/6J (P = 0.13), although the variances of the groups were significantly different. Blast exposure in J:DO mice results in a density change of 558.6 ± 440.5 BRN3A-positive RGCs/mm2 (mean ± SD)., Conclusions: The changes in retinal outcomes had greater variance in outbred mice than what has been reported, and largely replicated herein, for inbred mice. These results demonstrate that the RGC response to blast injury is highly dependent upon genetic background.

Blunt-force traumatic brain injuries (TBI) are the most common form of head trauma, which spans a range of severities and results in complex and heterogenous secondary effects. While there is no mechanism to replace or regenerate the lost neurons following a TBI in humans, zebrafish possess the ability to regenerate neurons throughout their body, including the brain. To examine the breadth of pathologies exhibited in zebrafish following a blunt-force TBI and to study the mechanisms underlying the subsequent neuronal regenerative response, we modified the commonly used rodent Marmarou weight drop for the use in adult zebrafish. Our simple blunt-force TBI model is scalable, inducing a mild, moderate, or severe TBI, and recapitulates many of the phenotypes observed following human TBI, such as contact- and post-traumatic seizures, edema, subdural and intracerebral hematomas, and cognitive impairments, each displayed in an injury severity-dependent manner. TBI sequelae, which begin to appear within minutes of the injury, subside and return to near undamaged control levels within 7 days post-injury. The regenerative process begins as early as 48 hours post-injury (hpi), with the peak cell proliferation observed by 60 hpi. Thus, our zebrafish blunt-force TBI model produces characteristic primary and secondary injury TBI pathologies similar to human TBI, which allows for investigating disease onset and progression, along with the mechanisms of neuronal regeneration that is unique to zebrafish.

Severe traumatic brain injury is a common problem. Current practices focus on the importance of early resuscitation, transfer to high-volume centers, and provider expertise across multiple specialties. In the emergency department, patients should receive urgent intracranial imaging and consideration for tranexamic acid. Close observation in the intensive care unit environment helps identify problems, such as seizure, intracranial pressure crisis, and injury progression. In addition to traditional neurologic examination, patients benefit from use of intracranial monitors. Monitors gather physiologic data on intracranial and cerebral perfusion pressures to help guide therapy. Brain tissue oxygenation monitoring and cerebromicrodialysis show promise in studies., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Traumatic brain injury (TBI) is a public health problem in Ethiopia. More knowledge about the epidemiology and neurosurgical management of TBI patients is needed to identify possible focus areas for quality improvement and preventive efforts., Methods: This prospective cross-sectional study (2012-2016) was performed at the 4 teaching hospitals in Addis Ababa, Ethiopia. All surgically treated TBI patients were included, and data on clinical presentation, injury types, and trauma causes were collected., Results: We included 1087 patients (mean age 29 years; 8.7% females; 17.1% <18 years old). Only 15.5% of TBIs were classified as severe (Glasgow Coma Scale score 3-8). Depressed skull fracture (44.9%) and epidural hematoma (39%) were the most frequent injuries. Very few patients had polytrauma (3.1%). Assault was the most common injury mechanism (69.9%) followed by road traffic accidents (15.8%) and falls (8.1%). More than 80% of patients came from within 200 km of the hospitals, but the median time to admission was 24 hours. Most assault victims (80.4%) were injured >50 km from the hospitals, whereas 46% of road traffic accident victims came from the urban area. Delayed admission was associated with higher Glasgow Coma Scale scores and nonsevere TBI (P < 0.01)., Conclusions: The injury panorama, delayed admission, and small number of operations performed for severe TBI are linked to a substantial patient selection bias both before and after hospital admission. Our results also suggest that there should be a geographical framework for tailored guidelines, preventive efforts, and development of prehospital and hospital services., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The secondary injury process after traumatic brain injury (TBI) results in motor dysfunction, cognitive and emotional impairment, and poor outcomes. These injury cascades include excitotoxic injury, mitochondrial dysfunction, oxidative stress, ion imbalance, inflammation, and increased vascular permeability. Electron microscopy is an irreplaceable tool to understand the complex pathogenesis of TBI as the secondary injury is usually accompanied by a series of pathologic changes at the ultra-micro level of the brain cells. These changes include the ultrastructural changes in different parts of the neurons (cell body, axon, and synapses), glial cells, and blood-brain barrier, etc. In view of the current difficulties in the treatment of TBI, identifying the changes in subcellular structures can help us better understand the complex pathologic cascade reactions after TBI and improve clinical diagnosis and treatment. The purpose of this review is to summarize and discuss the ultrastructural changes related to neurons (e.g., condensed mitochondrial membrane in ferroptosis), glial cells, and blood-brain barrier in the existing reports of TBI, to deepen the in-depth study of TBI pathomechanism, hoping to provide a future research direction of pathogenesis and treatment, with the ultimate aim of improving the prognosis of patients with TBI.

Traumatic brain injury (TBI), also known as intracranial injury, occurs when an external force injures the brain. This study aimed to analyze the factors affecting the presence of TBI in the elderly occupants of motor vehicle crashes. We defined elderly occupants as those more than 55 years old. Damage to the vehicle was presented using the Collision Deformation Classification (CDC) code by evaluation of photos of the damaged vehicle, and a trauma score was used for evaluation of the severity of the patient's injury. A logistic regression model was used to identify factors affecting TBI in elderly occupants and a predictive model was constructed. We performed this study retrospectively and gathered all the data under the Korean In-Depth Accident Study (KIDAS) investigation system. Among 3697 patients who visited the emergency room in the regional emergency medical center due to motor vehicle crashes from 2011 to 2018, we analyzed the data of 822 elderly occupants, which were divided into two groups: the TBI patients (N = 357) and the non-TBI patients (N = 465). According to multiple logistic regression analysis, the probabilities of TBI in the elderly caused by rear-end (OR = 1.833) and multiple collisions (OR = 1.897) were higher than in frontal collision. Furthermore, the probability of TBI in the elderly was 1.677 times higher in those with unfastened seatbelts compared to those with fastened seatbelts (OR = 1.677). This study was meaningful in that it incorporated several indicators that affected the occurrence of the TBI in the elderly occupants. In addition, it was performed to determine the probability of TBI according to sex, vehicle type, seating position, seatbelt status, collision type, and crush extent using logistic regression analysis. In order to derive more precise predictive models, it would be needed to analyze more factors for vehicle damage, environment, and occupant injury in future studies.

Background: E-bike usage is increasingly popular and concerns about e-bike-related injuries and safety have risen as more injured e-bikers attend the emergency department (ED). Traumatic brain injury (TBI) is the main cause of severe morbidity and mortality in bicycle-related accidents. This study compares the frequency and severity of TBI after an accident with an e-bike or classic bicycle among patients treated in the ED., Methods: This was a prospective cohort study of patients with bicycle-related injuries attending the ED of a level 1 trauma centre in the Netherlands between June 2016 and May 2017. The primary outcomes were frequency and severity of TBI (defined by the Abbreviated Injury Scale head score ≥1). Injury Severity Score, surgical intervention, hospitalisation and 30-day mortality were secondary outcomes. Independent risk factors for TBI were identified with multiple logistic regression., Results: We included 834 patients, of whom there were 379 e-bike and 455 classic bicycle users. The frequency of TBI was not significantly different between the e-bike and classic bicycle group (respectively, n=56, 15% vs n=73, 16%; p=0.61). After adjusting for age, gender, velocity, anticoagulation use and alcohol intoxication the OR for TBI with an e-bike compared with classic bicycle was 0.90 (95% CI 0.56 to 1.45). Independent of type of bicycle, TBI was more likely if velocity was 26-45 km/hour, OR 8.14 (95% CI 2.36 to 28.08), the patient was highly alcohol intoxicated, OR 7.02 (95% CI 2.88 to 17.08) or used anticoagulants, OR 2.18 (95% CI 1.20 to 3.97). TBI severity was similar in both groups (p=0.65): eight e-bike and seven classic bicycle accident victims had serious TBI., Conclusion: The frequency and severity of TBI among patients treated for bicycle-related injuries at our ED was similar for e-bike and classic bicycle users. Velocity, alcohol intoxication and anticoagulant use were the main determinants of the risk of head injury regardless of type of bicycle used., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality among military service members and civilians in the United States. Despite significant advances in the understanding of TBI pathophysiology, several clinical reports indicate that multiple genetic and epigenetic factors can influence outcome. Homocysteine (HCY) is a non-proteinogenic amino acid, the catabolism of which can be dysregulated by stress, lifestyle, aging, or genetic abnormalities leading to hyperhomocysteinemia (HHCY). HHCY is a neurotoxic condition and a risk factor for multiple neurological and cardiovascular disorders that occurs when HCY levels is clinically > 15 µM. Although the deleterious impact of HHCY has been studied in human and animal models of neurological disorders such as stroke, Alzheimer's disease and Parkinson's disease, it has not been addressed in TBI models. This study tested the hypothesis that HHCY has detrimental effects on TBI pathophysiology. Moderate HHCY was induced in adult male Sprague Dawley rats via daily administration of methionine followed by impact-induced traumatic brain injury. In this model, HHCY increased oxidative stress, upregulated expression of proteins that promote blood coagulation, exacerbated TBI-associated blood-brain barrier dysfunction and promoted the infiltration of inflammatory cells into the cortex. We also observed an increase of brain injury-induced lesion size and aggravated anxiety-like behavior. These findings show that moderate HHCY exacerbates TBI outcomes and suggest that HCY catabolic dysregulation may be a significant biological variable that could contribute to TBI pathophysiology heterogeneity.

Objectives: Annually, the CDC reports that 2.5 million Emergency Department (ED) visits occur due to Traumatic Brain Injuries (TBI) with nearly 75% classified as mild TBI (mTBI). Generally, these injuries are thought to be under recognized. This study was done to determine the proportion of patients, who were considered high risk for an mTBI, that had documentation of an mTBI evaluation., Methods: A prospective cross-section of patients was identified using a 3-question screen at the time of triage: did an injury occur; was the mechanism consistent with mTBI; and was there a period of altered mental status. Chart review was completed for these patients who were thought to meet a minimum threshold warranting an evaluation for mTBI., Results: 38,621 patients were screened over 16 weeks, of whom 441 (1.14%) were identified as being high risk for having an mTBI and met inclusion criteria. Recommended portions of an mTBI evaluation occurred in fewer than 50% of patients. In total, 98 subjects were diagnosed with an mTBI, and 49 received mTBI discharge instructions. The odds ratio for the subgroup of patients who had documented criteria sufficient for diagnosis revealed that an isolated head injury increased a patient's odds of a documented diagnosis by 2.1 times (95%, 1.3-3.4)., Conclusions: Many patients with a possible mTBI did not have significant portions of an mTBI evaluation documented, and roughly half of the patients with a documented mTBI diagnosis did not receive discharge education. Changes in clinicians' approach to mTBI must occur to ensure patients receive appropriate evaluations, management, and education., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Traumatic brain injuries are common among refugees and asylum-seekers and can result from a range of etiologies, including intimate partner violence, gang violence, war-related trauma, and torture. Regardless of the cause, these injuries often result in a host of neuropsychiatric and other symptoms that may complicate individuals' subsequent health outcomes. For asylum-seekers, documenting prior head trauma is essential to the legal process, since traumatic brain injuries and their subsequent effects on memory and cognition may affect the ability to provide thorough testimony. Using three case vignettes, we explore how to approach the forensic evaluation of asylum-seekers with a history of traumatic brain injury, illustrating the range of etiologies and sequelae of traumatic brain injury in this complex population., (Copyright © 2021. Published by Elsevier Ltd.)

The consequences of blast-induced traumatic brain injury (bTBI) on the blood-brain barrier (BBB) and components of the neurovascular unit are an area of active research. In this study we assessed the time course of BBB integrity in anesthetized rats exposed to a single blast overpressure of 130 kPa (18.9 PSI). BBB permeability was measured in vivo via intravital microscopy by imaging extravasation of fluorescently labeled tracers (40 kDa and 70 kDa molecular weight) through the pial microvasculature into brain parenchyma at 2-3 h, 1, 3, 14, or 28 days after the blast exposure. BBB structural changes were assessed by immunostaining and molecular assays. At 2-3 h and 1 day after blast exposure, significant increases in the extravasation of the 40 kDa but not the 70 kDa tracers were observed, along with differential reductions in the expression of tight junction proteins (occludin, claudin-5, zona occluden-1) and increase in the levels of the astrocytic water channel protein, AQP-4, and matrix metalloprotease, MMP-9. Nearly all of these measures were normalized by day 3 and maintained up to 28 days post exposure. These data demonstrate that blast-induced changes in BBB permeability are closely coupled to structural and functional components of the BBB.

Traumatic brain injury (TBI) is traditionally characterized by primary and secondary injury phases, both contributing to pathological and morphological changes. The mechanisms of damage and chronic consequences of TBI remain to be fully elucidated, but synaptic homeostasis disturbances and impaired energy metabolism are proposed to be a major contributor. It has been proposed that an increase of extracellular (eATP) adenosine triphosphate (ATP) in the area immediately surrounding impact may play a pivotal role in this sequence of events. After tissue injury, rupture of cell membranes allows release of intracellular ATP into the extracellular space, triggering a cascade of toxic events and inflammation. ATP is a ubiquitous messenger; however, simple and reliable techniques to measure its concentration have proven elusive. Here, we integrate a sensitive bioluminescent eATP sensor known as pmeLUC, with a controlled cortical impact mouse model to monitor eATP changes in a living animal after injury. Using the pmeLUC probe, a rapid increase of eATP is observed proximal to the point of impact within minutes of the injury. This event is significantly attenuated when animals are pretreated with an ATP hydrolyzing agent (apyrase) before surgery, confirming the contribution of eATP. This new eATP reporter could be useful for understanding the role of eATP in the pathogenesis in TBI and may identify a window of opportunity for therapeutic intervention.

Although traumatic brain injury (TBI) causes hospitalizations and mortality worldwide, there are no approved neuroprotective treatments, partly due to a poor understanding of the molecular mechanisms underlying TBI neuropathology and neuroprotection. We previously reported that the administration of low-dose methamphetamine (MA) induced significant functional/cognitive improvements following severe TBI in rats. We further demonstrated that MA mediates neuroprotection in part, via dopamine-dependent activation of the PI3K-AKT pathway. Here, we further investigated the proteomic changes within the rat cortex and hippocampus following mild TBI (TM), severe TBI (TS), or severe TBI plus MA treatment (TSm) compared to sham operated controls. We identified 402 and 801 altered proteins (APs) with high confidence in cortical and hippocampal tissues, respectively. The overall profile of APs observed in TSm rats more closely resembled those seen in TM rather than TS rats. Pathway analysis suggested beneficial roles for acute signaling through IL-6, TGFβ, and IL-1β. Moreover, changes in fibrinogen levels observed in TSm rats suggested a potential role for these proteins in reducing/preventing TBI-induced coagulopathies. These data facilitate further investigations to identify specific pathways and proteins that may serve as key targets for the development of neuroprotective therapies.

Introduction: Treatment of traumatic brain injury (TBI) with granulocyte colony-stimulating factor (G-CSF) has been shown to enhance brain repair by direct neurotrophic actions on neural cells and by modulating the inflammatory response. Administration of cannabinoids after TBI has also been reported to enhance brain repair by similar mechanisms. Objectives: The primary objective of this study was to test the hypothesis that G-CSF mediates brain repair by interacting with the endocannabinoid system. Methods and Results: (i) Mice that underwent controlled cortical impact (CCI) were treated with G-CSF for 3 days either alone or in the presence of selective cannabinoid receptor 1 (CB1-R) or cannabinoid receptor 2 (CB2-R) agonists and antagonists. The trauma resulted in decreased expression of CB1-R and increased expression of CB2-R in the cortex, striatum, and hippocampus. Cortical and striatal levels of the major endocannabinoid ligand, 2-arachidonoyl-glycerol, were also increased by the CCI. Administration of the hematopoietic cytokine, G-CSF, following TBI, resulted in mitigation or reversal of trauma-induced CB1-R downregulation and CB2-R upregulation in the three brain regions. Treatment with CB1-R agonist (WIN55) or CB2-R agonist (HU308) mimicked the effects of G-CSF. (ii) Pharmacological blockade of CB1-R or CB2-R was not effective in preventing G-CSF's mitigation or reversal of trauma-induced alterations in these receptors. Conclusions: These results suggest that cellular and molecular mechanisms that mediate subacute effects of G-CSF do not depend on activation of CB1 or CB2 receptors. Failure of selective CB receptor antagonists to prevent the effects of G-CSF in this model has to be accepted with caution. CB receptor antagonists can interact with other CB and non-CB receptors. Investigation of the role of CB receptors in this TBI model will require studies with CB1-R and in CB2-R knockout mice to avoid nonspecific interaction of CB receptor agents with other receptors., Competing Interests: No competing financial interests exist., (Copyright 2021, Mary Ann Liebert, Inc., publishers.)

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.)

Soccer, as a contact sport, exposes players to repetitive head impacts, especially through heading the ball. The question of a long-term brain cumulative effect remains. Our objective was to determine whether exposure to head impacts over one soccer season was associated with changes in functional brain connectivity at rest, using magnetic resonance imaging (MRI). In this prospective cohort study, 10 semi-professional men soccer players, aged 18-25 years, and 20 age-matched men athletes without a concussion history and who do not practice any contact sport were recruited in Bordeaux (France). Exposure to head impacts per soccer player during competitive games over one season was measured using video analysis. Resting-state functional magnetic resonance imaging data were acquired for both groups at two times, before and after the season. With a seed-based analysis, resting-state networks that have been intimately associated with aspects of cognitive functioning were investigated. The results showed a mean head impacts of 42 (±33) per soccer player over the season, mainly intentional head-to-ball impacts and no concussion. No head impact was found among the other athletes. The number of head impacts between the two MRI acquisitions before and after the season was associated with increased connectivity within the default mode network and the cortico-cerebellar network. In conclusion, our findings suggest that the brain functioning changes over one soccer season in association with exposure to repetitive head impacts., (© 2020 Wiley Periodicals LLC.)

Rationale: The recently discovered meningeal lymphatic vessels (mLVs) have been proposed to be the missing link between the immune and the central nervous system. The role of mLVs in modulating the neuro-immune response following a traumatic brain injury (TBI), however, has not been analyzed. Parenchymal T lymphocyte infiltration has been previously reported as part of secondary events after TBI, suggestive of an adaptive neuro-immune response. The phenotype of these cells has remained mostly uncharacterized. In this study, we identified subpopulations of T cells infiltrating the perilesional areas 30 days post-injury (an early-chronic time point). Furthermore, we analyzed how the lack of mLVs affects the magnitude and the type of T cell response in the brain after TBI., Methods: TBI was induced in K14-VEGFR3-Ig transgenic (TG) mice or in their littermate controls (WT; wild type), applying a controlled cortical impact (CCI). One month after TBI, T cells were isolated from cortical areas ipsilateral or contralateral to the trauma and from the spleen, then characterized by flow cytometry. Lesion size in each animal was evaluated by MRI., Results: In both WT and TG-CCI mice, we found a prominent T cell infiltration in the brain confined to the perilesional cortex and hippocampus. The majority of infiltrating T cells were cytotoxic CD8+ expressing a CD44 hi CD69+ phenotype, suggesting that these are effector resident memory T cells. K14-VEGFR3-Ig mice showed a significant reduction of infiltrating CD4+ T lymphocytes, suggesting that mLVs could be involved in establishing a proper neuro-immune response. Extension of the lesion (measured as lesion volume from MRI) did not differ between the genotypes. Finally, TBI did not relate to alterations in peripheral circulating T cells, as assessed one month after injury., Conclusions: Our results are consistent with the hypothesis that mLVs are involved in the neuro-immune response after TBI. We also defined the resident memory CD8+ T cells as one of the main population activated within the brain after a traumatic injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wojciechowski, Virenque, Vihma, Galbardi, Rooney, Keuters, Antila, Koistinaho and Noe.)

Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [ 11 C]PBR28 and [ 18 F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [ 11 C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [ 18 F]flumazenil is a radioligand for GABA A -benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [ 11 C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [ 18 F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [ 11 C]PBR28 and [ 18 F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment.

The ability to infer other persons' mental states, "Theory of Mind" (ToM), is a key function of social cognition and is needed when interpreting the intention of others. ToM is associated with a network of functionally related regions, with reportedly key prominent hubs located in the dorsolateral prefrontal cortex (dlPFC) and the temporoparietal junction (TPJ). The involvement of (mainly the right) TPJ in ToM is based primarily on functional imaging studies that provide correlational evidence for brain-behavior associations. In this lesion study, we test whether certain brain areas are necessary for intact ToM performance. We investigated individuals with penetrating traumatic brain injury (n = 170) and healthy matched controls (n = 30) using voxel-based lesion-symptom mapping (VLSM) and by measuring the impact of a given lesion on white matter disconnections. ToM performance was compared between five patient groups based on lesion location: right TPJ, left TPJ, right dlPFC, left dlPFC, and other lesion, as well as healthy controls. The only group to present with lower ToM abilities was the one with lesions in the right dlPFC. Similarly, VLSM analysis revealed a main cluster in the right frontal middle gyrus and a secondary cluster in the left inferior parietal gyrus. Last, we found that disconnection of the left inferior longitudinal fasciculus and right superior longitudinal fasciculus were associated with poor ToM performance. This study highlights the importance of lesion studies in complementing functional neuroimaging findings and supports the assertion that the right dlPFC is a key region mediating mental state attribution., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Aim: To investigate whether Nimodipine (N) and Nigella sativa (NS) oil have protective, antioxidant effects in brain injury caused by experimental head trauma., Material and Methods: Fifty albino Wistar rats were randomly divided into 5 groups that underwent experimental head trauma. Oxidative parameters were compared in the serum and brain tissue of the different groups. In addition, apoptosis and caspase-3 immunoreactivity were evaluated by histopathological examination., Results: Serum total antioxidant status (TAS) levels were significantly increased in N and N+NS groups when compared with controls (p=0.001, p < 0.01). Tissue TAS levels were significantly higher in the NS and N+NS groups compared to controls (p=0.001, p < 0.01). Total oxidant status levels in the brain tissue were significantly higher in the NS group than in the control group (p=0.021)., Conclusion: N and NS were shown to significantly reduce the occurrence of oxidative stress in secondary brain injury due to head trauma. We also found that apoptosis levels decreased in response to N, NS and N+NS treatments after head trauma.

Drosophila models have been instrumental in providing insights into molecular mechanisms of neurodegeneration, with wide application to human disease. The brain degeneration associated with traumatic brain injury (TBI) has been modeled in Drosophila using devices that inflict trauma on multiple parts of the fly body, including the head. However, the injuries produced by these models are not specific in location and are inconsistent between individual animals. We have recently developed a device that can be used to inflict controlled head injury to flies, resulting in physiological responses that are remarkably similar to those observed in humans with TBI. This protocol describes the construction, calibration and use of the Drosophila TBI (dTBI) device, a platform that employs a piezoelectric actuator to reproducibly deliver a force in order to briefly compress the fly head against a metal surface. The extent of head compression can be controlled through an electrical circuit, allowing the operator to set different levels of injury. The entire device can be assembled and calibrated in under a week. The device components and the necessary electrical tools are readily available and cost ~$800. The dTBI device can be used to harness the power of Drosophila genetics and perform large-scale genetic or pharmacological screens, using a 7-d post-injury survival curve to identify modifiers of injury.

Introduction: Blast-induced traumatic brain injuries (bTBIs) are increasingly frequent in civilian settings. We present the first study of individuals with bTBI in Iraq. The study focuses on one of the deadliest suicide car bomb attacks in Iraq and uses it to show the devastating nature of bTBIs., Methods: This study was conducted at the Neurosurgery Teaching Hospital in Baghdad, Iraq. A retrospective chart analysis of patients with bTBI admitted to the Neurosurgery Teaching Hospital was performed. Measured parameters included patients' demographics, initial presentation, injury patterns, hospital course, surgical management, and outcomes., Results: A total of 75 patients with bTBI were included in this study, 19 of whom died in the emergency room. The remaining 56 patients were admitted to the hospital. Of those patients, 68.6% (n = 39) underwent surgery, and 30.4% were managed conservatively. A modified, tailored triaging system was implemented. All surgery was guided by the principles of damage control neurosurgery. In addition, 76.9% and 46.2% of patients underwent corticectomy and decompressive craniectomy, respectively. Dural venous sinus repair was performed in 17.9% of patients, and 30.7% of the operations entailed additional steps to control major (arterial) cerebrovascular bleeding. The net bTBI-related complication rate was 76%. The total mortality was 48%. Of survivors, 10.7% (n = 8) were discharged with a severe disability. Overall, good outcomes were achieved in 41.3% of the patients., Conclusions: This study sheds light on the devastating nature of bTBIs. Neurosurgeons worldwide need to be mindful of the unique triaging, diagnostic, and management requirements of these injuries., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The dural venous sinuses play an integral role in draining venous blood from the cranial cavity. As a result of the sinuses anatomical location, they are of significant importance when evaluating the mechanopathology of traumatic brain injury (TBI). Despite the importance of the dural venous sinuses in normal neurophysiology, no mechanical analyses have been conducted on the tissues. In this study, we conduct mechanical and structural analysis on porcine dural venous sinus tissue to help elucidate the tissues' function in healthy and diseased conditions. With longitudinal elastic moduli values ranging from 33 to 58 MPa, we demonstrate that the sinuses exhibit higher mechanical stiffness than that of native dural tissue, which may be of interest to the field of TBI modelling. Furthermore, by employing histological staining and a colour deconvolution protocol, we show that the sinuses have a collagen-dominant extracellular matrix, with collagen area fractions ranging from 84 to 94%, which likely explains the tissue's large mechanical stiffness. In summary, we provide the first investigation of the dural venous sinus mechanical behaviour with accompanying structural analysis, which may aid in understanding TBI mechanopathology.

Background: Ethnic disparities have been associated with injury and mortality. The impact of ethnicity on head and neck injury (HNI), traumatic brain injury (TBI), in-hospital mortality and resource utilization following a motorcycle crash (MCC) is undetermined. This study explored the influence of ethnicity in these aspects and the effect of helmet use on HNI and TBI following a MCC., Methods: The National Trauma Registry provided hospitalization data on motorcycle riders and passengers between 2008 and 2017. Ethnicity was classified as Jews or Arabs, the two major ethnic groups in Israel. Univariate followed by multivariable logistic models were applied to examine ethnic disparities. Mediation effect was tested by structural equation modeling., Results: Among 6073 MCC casualties, Arabs had increased odds of HNI (OR = 1.37,95% CI = 1.12-1.65) and TBI (OR = 1.51,95%CI = 1.12-1.99), and a six-fold decreased odds of helmet use (OR = 0.16,95%CI = 0.12-0.22). The HNI and TBI associations with ethnicity were mediated by helmet use. Arabs had significantly higher odds for admission to intensive care unit (OR = 1.36,95%CI = 1.00-1.83), and lower odds for ambulance evacuation (OR = 0.73,95%CI = 0.61-0.89) and discharge to rehabilitation (OR = 0.55,95%CI = 0.39-0.7). In-hospital mortality was not associated with ethnicity., Conclusions: Helmet non-use is an important etiologic factor associated with motorcycle-related HNI and TBI among Arabs. While in Israel, ethnic equality exists in in-hospital health care, disparities in ambulance and rehabilitation utilization was found. Intervention programs should target the Arab population and focus on helmet compliance.

Introduction: Motorcycles are colloquially referred to as "donorcycles" among medical staff. However, the actual impact of helmet laws and helmet use on organ donation is unknown. Michigan's 35-year-old universal helmet law (UHL) was repealed in April 2012 and replaced by a partial-helmet law. We hypothesized that there would be an increase in organ donation rates from unhelmeted motorcyclist fatalities., Methods: Michigan's Gift of Life Michigan organ donation database was queried from April 2008 through May 2015 in conjunction with the Michigan Trauma Quality Improvement Program database from the same time period. All in-hospital motorcycle crash fatalities were examined., Results: A three-fold increase was found in the rate of organ donation for unhelmeted motorcyclists compared to helmeted motorcyclists (p = 0.006). Motorcycle crash fatalities tended to be younger in age after the UHL repeal with an average age of 32.8 years versus 40.8, however, this finding was not statistically significant (p = 0.071). Additionally, there was no significant difference in organ donation rates pre-UHL repeal (2008-2012) versus post-repeal (2012-2015)., Conclusions: This is the first study to demonstrate an increased rate of organ donation among unhelmeted motorcyclist fatalities compared to helmeted rider fatalities. There was no significant increase in the rate of organ donation following the Michigan UHL repeal. However, we identified that some motorcycle crash fatalities were from illegally unhelmeted riders in the past, prior to the repeal. Practical Application: Unhelmeted motorcyclists are three times more likely than helmeted riders to become organ donors, possibly due to the well documented increase in severe traumatic brain injuries in this population. From a public health perspective, helmets should be required for all motorcyclists and efforts to advocate in favor of helmet legislation should be supported by trauma systems and health professionals., (Copyright © 2020.)

Background: This study aimed to establish the minimal clinically important difference (MCID) for the Fugl-Meyer Motor Scale (FMMS) and the Disability Rating Scale (DRS) to evaluate interventions in patients with motor deficits in the chronic phase after traumatic brain injury (TBI)., Methods: MCIDs were established with a structured expert consultation process, the RAND/UCLA modified Delphi method. This process consisted of a literature review and input from a 10-person, multidisciplinary expert panel. The experts were asked to rate meaningfulness of improvements in hypothetical patients and numeric changes via two rounds of ratings and an in-person meeting., Results: The estimated MCIDs were six and five points on the FMMS Upper and Lower Extremity Scale, respectively, and one point on the DRS. The experts argued against establishing an MCID for the combined FMMS because the same change was more likely to be meaningful if concentrated in one extremity and because a meaningful improvement in one extremity implies meaningfulness irrespective of the changes in the other., Conclusions: This study is the first to establish MCIDs for the FMMS and the DRS in the chronic phase after TBI. The results may be helpful for the design and interpretation of clinical trials of interventions.