Effects Of Brain Injury Research Articles

Retrospective study evaluating safety, clinical effect, and dosing of dalteparin for the treatment of venous thromboembolism in term neonates.

There is an increased risk of venous thromboembolism (VTE) among neonates due to their unique hemostatic system. However, there is lack of approved treatment options for VTE in neonatal population. Importantly, dalteparin, a low molecular weight heparin approved for pediatric VTE in children ≥1month of age, has also been used for the treatment of neonatal VTE. Based on the request from the Food and Drug Administration, this retrospective study aimed to characterize the safety, clinical effects, and dosing of dalteparin for treatment of VTE among neonates. Data from electronic medical records for neonates (born ≥35weeks of gestation) treated with dalteparin for VTE between January 2010 and December 2021 were collected. The data assessed included bleeding and deterioration in hematological biomarkers among other adverse events, changes in relevant factor antifactor Xa (anti-Xa) levels and VTE status, and dosing of dalteparin and corresponding anti-Xa assay levels. Sixteen neonates from five participating sites in the United Kingdom were included. There were no bleeding events or deaths. Only one serious adverse event of hypoglycemic brain injury (unrelated to dalteparin) was documented in a patient with a history of hyperinsulinism. Median (range) daily dose of dalteparin at initiation was 309 (297-314)IU/kg. Eight of 16 neonates achieved therapeutic anti-Xa level, including two patients who did so after the first dose. Dalteparin treatment in neonates raised no major safety concerns. Larger cohort studies may help provide further insights on clinical effects of dalteparin for neonatal VTE.

Calcium and Non-Penetrating Traumatic Brain Injury: A Proposal for the Implementation of an Early Therapeutic Treatment for Initial Head Insults.

Finding an effective treatment for traumatic brain injury is challenging for multiple reasons. There are innumerable different causes and resulting levels of damage for both penetrating and non-penetrating traumatic brain injury each of which shows diverse pathophysiological progressions. More concerning is that disease progression can take decades before neurological symptoms become obvious. Currently, the primary treatment for non-penetrating mild traumatic brain injury, also called concussion, is bed rest despite the fact the majority of emergency room visits for traumatic brain injury are due to this mild form. Furthermore, one-third of mild traumatic brain injury cases progress to long-term serious symptoms. This argues for the earliest therapeutic intervention for all mild traumatic brain injury cases which is the focus of this review. Calcium levels are greatly increased in damaged brain regions as a result of the initial impact due to tissue damage as well as disrupted ion channels. The dysregulated calcium level feedback is a diversity of ways to further augment calcium neurotoxicity. This suggests that targeting calcium levels and function would be a strong therapeutic approach. An effective calcium-based traumatic brain injury therapy could best be developed through therapeutic programs organized in professional team sports where mild traumatic brain injury events are common, large numbers of subjects are involved and professional personnel are available to oversee treatment and documentation. This review concludes with a proposal with that focus.

Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi-Cohort Mega-Analysis.

The long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. Given evidence that a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using structural magnetic resonance imaging (MRI) data. Complicated mild, moderate, and severe TBI (cmsTBI) is associated with a higher predicted age difference (PAD), but the progression of PAD over time remains unclear. We sought to examine whether PAD increases as a function of time since injury (TSI) and if injury severity and sex interacted to influence this progression. Through the ENIGMA Adult Moderate and Severe (AMS)-TBI working group, we examine the largest TBI sample to date (n = 343), along with controls, for a total sample size of n = 540, to replicate and extend prior findings in the study of TBI brain age. Cross-sectional T1w-MRI data were aggregated across 7 cohorts, and brain age was established using a similar brain age algorithm to prior work in TBI. Findings show that PAD widens with longer TSI, and there was evidence for differences between sexes in PAD, with men showing more advanced brain age. We did not find strong evidence supporting a link between PAD and cognitive performance. This work provides evidence that changes in brain structure after cmsTBI are dynamic, with an initial period of change, followed by relative stability in brain morphometry, eventually leading to further changes in the decades after a single cmsTBI. ANN NEUROL 2024;96:365-377.

Maresin 1 Activates LGR6 to Alleviate Neuroinflammation via the CREB/JMJD3/IRF4 Pathway in a Rat Model of Subarachnoid Hemorrhage

Neuroinflammation is an early event of brain injury after subarachnoid hemorrhage (SAH). Whether the macrophage mediators in resolving inflammation 1 (MaR1) is involved in SAH pathogenesis is unknown. In this study, 205 male Sprague-Dawley rats were subjected to SAH via endovascular perforation in the experimental and control groups. MaR1 was dosed intranasally at 1 h after SAH, with LGR6 siRNA and KG-501, GSK-J4 administered to determine the signaling pathway. Neurobehavioral, histological and biochemical data were obtained from the animal groups with designated treatments. The results showed: (i) The leucine-rich repeat containing G protein–coupled receptor 6 (LGR6) was decreased after SAH and reached to the lowest level at 24 h after SAH. Jumonji d3 (JMJD3) protein levels tended to increase and peaked at 24 h after SAH. LGR6 and JMJD3 expression were co-localized with microglia. (ii) MaR1 administration mitigated short-term neurological deficits, brain edema and long-term neurobehavioral performance after SAH, and attenuated microglial activation and neutrophil infiltration. (iii) Knockdown of LGR6, inhibition of CREB phosphorylation or JMJD3 activity abolished the anti-neuroinflammatory effect of MaR1 on the expression of CREB, CBP, JMJD3, IRF4, IRF5, IL-1β, IL-6 and IL-10, thus prevented microglial activation and neutrophil infiltration. Together, the results show that MaR1 can activate LGR6 and affect CREB/JMJD3/IRF4 signaling to attenuate neuroinflammation after SAH, pointing to a potential pharmacological utility in this disorder.

Spatial lipidomics maps brain alterations associated with mild traumatic brain injury.

Traumatic brain injury (TBI) is a global public health problem with 50-60 million incidents per year, most of which are considered mild (mTBI) and many of these repetitive (rmTBI). Despite their massive implications, the pathologies of mTBI and rmTBI are not fully understood, with a paucity of information on brain lipid dysregulation following mild injury event(s). To gain more insight on mTBI and rmTBI pathology, a non-targeted spatial lipidomics workflow utilizing high resolution mass spectrometry imaging was developed to map brain region-specific lipid alterations in rats following injury. Discriminant multivariate models were created for regions of interest including the hippocampus, cortex, and corpus callosum to pinpoint lipid species that differentiated between injured and sham animals. A multivariate model focused on the hippocampus region differentiated injured brain tissues with an area under the curve of 0.99 using only four lipid species. Lipid classes that were consistently discriminant included polyunsaturated fatty acid-containing phosphatidylcholines (PC), lysophosphatidylcholines (LPC), LPC-plasmalogens (LPC-P) and PC potassium adducts. Many of the polyunsaturated fatty acid-containing PC and LPC-P selected have never been previously reported as altered in mTBI. The observed lipid alterations indicate that neuroinflammation and oxidative stress are important pathologies that could serve to explain cognitive deficits associated with rmTBI. Therapeutics which target or attenuate these pathologies may be beneficial to limit persistent damage following a mild brain injury event.

MR imaging and outcome in neonatal HIBD models are correlated with sex: the value of diffusion tensor MR imaging and diffusion kurtosis MR imaging.

Hypoxic-ischemic encephalopathy can lead to lifelong morbidity and premature death in full-term newborns. Here, we aimed to determine the efficacy of diffusion kurtosis (DK) [mean kurtosis (MK)] and diffusion tensor (DT) [fractional anisotropy (FA), mean diffusion (MD), axial diffusion (AD), and radial diffusion (RD)] parameters for the early diagnosis of early brain histopathological changes and the prediction of neurodegenerative events in a full-term neonatal hypoxic-ischemic brain injury (HIBD) rat model. The HIBD model was generated in postnatal day 7 Sprague-Dawley rats to assess the changes in DK and DT parameters in 10 specific brain structural regions involving the gray matter, white matter, and limbic system during acute (12 h) and subacute (3 d and 5 d) phases after hypoxic ischemia (HI), which were validated against histology. Sensory and cognitive parameters were assessed by the open field, novel object recognition, elevated plus maze, and CatWalk tests. Repeated-measures ANOVA revealed that specific brain structures showed similar trends to the lesion, and the temporal pattern of MK was substantially more varied than DT parameters, particularly in the deep gray matter. The change rate of MK in the acute phase (12 h) was significantly higher than that of DT parameters. We noted a delayed pseudo-normalization for MK. Additionally, MD, AD, and RD showed more pronounced differences between males and females after HI compared to MK, which was confirmed in behavioral tests. HI females exhibited anxiolytic hyperactivity-like baseline behavior, while the memory ability of HI males was affected in the novel object recognition test. CatWalk assessments revealed chronic deficits in limb gait parameters, particularly the left front paw and right hind paw, as well as poorer performance in HI males than HI females. Our results suggested that DK and DT parameters were complementary in the immature brain and provided great value in assessing early tissue microstructural changes and predicting long-term neurobehavioral deficits, highlighting their ability to detect both acute and long-term changes. Thus, the various diffusion coefficient parameters estimated by the DKI model are powerful tools for early HIBD diagnosis and prognosis assessment, thus providing an experimental and theoretical basis for clinical treatment.

Demethylase FTO-Mediated m6A Modification of lncRNA MEG3 Activates Neuronal Pyroptosis via NLRP3 Signaling in Cerebral Ischemic Stroke.

Neuronal death following ischemia is the primary cause of death and disability in patients with ischemic stroke. N6-methyladenosine (m6A) modification plays essential role in various physiological and pathological conditions, but its role and mechanism in ischemic neuronal death remain unclear. In the present study, neuronal pyroptosis was an important event in brain injury caused by ischemic stroke, and the upregulation of long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) following cerebral ischemia was a key factor in activating ischemic neuronal pyroptosis via NLRP3/caspase-1/GSDMD signaling. Moreover, we first demonstrated that the demethylase fat mass and obesity-associated protein (FTO), which was decreased following ischemia, regulated MEG3 expression in an m6A-dependent manner by affecting its stability, thereby activating neuronal pyroptosis via NLRP3/caspase-1/GSDMD signaling, and ultimately leading to ischemic brain damage. Therefore, the present study provides new insights for the mechanism of ischemic stroke, and suggests that FTO may be a potential therapeutic target for ischemic stroke.

Predictors of Mortality and Functional recovery after severe traumatic brain injury: protocol for a prospective cohort study

Introduction: traumatic brain injury is a global public health problem due to its severity and high rates of morbimortality worldwide. Identifying predictors associated with increased mortality and unfavorable functional outcomes after the traumatic brain injury event is crucial for minimizing morbidity and mortality rates. Therefore, this study aims to establish a protocol to investigate the predictors of mortality and functional recovery after severe traumatic brain injury in Brazil. Methods: The study will include all patients admitted for severe traumatic brain injury (Glasgow Coma Scale ≤ 8) at the State Hospital of Urgency and Emergency, which is the referral trauma hospital of Espirito Santo. The outcomes of interest are hospital mortality and functional recovery 24 months after hospital discharge. Subjects will be followed up at seventy-two hours, three months, six months, twelve months, and twenty-four months after the trauma. Morbidity will be determined by assessing: 1) the level of motor and cognitive disability, 2) functional impairment and quality of life, and 3) aspects of rehabilitation treatment. Additionally, the traumatic brain injury load, estimated by the years of life lost, will be calculated. Discussion: the results of this study will help identify variables that can predict morbidity and mortality, as well as diagnostic and therapeutic targets for patients with severe traumatic brain injury. Furthermore, the findings will have practical implications for: 1) the development of public policies, 2) investments in hospital infrastructure 3) understanding the socioeconomic impact of functional loss in the individuals. Study registration: the study received approval from the Ethics Committee of the Federal University of Espirito Santo under protocol number 4.222.002 on August 18, 2020.

Targeting the JAK2-STAT3 pathway to inhibit cGAS-STING activation improves neuronal senescence after ischemic stroke

Neuroinflammation after cerebral ischemia is a key event in progressive brain injury after ischemic stroke. The JAK2/STAT3 pathway is pivotal for neuroinflammation; however, its role in brain senescence after ischemic stroke is unclear. Here, we report that inflammation is increased in the brains of C57BL/6 stroke mice. Treatment of ischemic stroke in adult mice with a JAK kinase inhibitor (AG490) alleviated neurobehavioral defects, reduced brain infarct volume, reduced expression of pro-inflammatory cytokines, and decreased activation of pro-inflammatory microglia. Moreover, AG490 treatment reduced oxidative DNA damage and cellular senescence in the brains of mice following ischemic stroke. Cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) were associated with inflammation and senescence. Furthermore, AG490 blocked cGAS/STING/NF-κBp65 expression. Overall, our results indicate that inhibition of JAK2/STAT3 can alleviate the negative neurological consequences of ischemic stroke, likely due to repression of cGAS/STING/NF-κB p65, leading to reduced neuroinflammation and neuronal senescence. Therefore, JAK2/STAT3 may represent a viable therapeutic target for preventing senescence after ischemic stroke.

Risk of secondary stroke subsequent to restarting aspirin in chronic stroke patients suffering from traumatic brain injury in Taiwan

Traumatic brain injury (TBI) is a silent epidemic that has been easily ignored. The safety and efficacy of restarting antiplatelet therapy after encountering traumatic brain injury (TBI) events remain a challenge. We explored the outcomes of restarting aspirin use on secondary stroke and mortality in patients with chronic stroke 4 weeks after suffering from a TBI episode in Taiwan. This study analyzed data from the National Health Insurance Research Database from January 2000 to December 2015. Overall, 136,211 individuals diagnosed with chronic stroke who suffered from acute TBI and received inpatient service were enrolled. The study outcomes were a competing risk of secondary stroke (ischemic and hemorrhagic) hospitalization and all-cause mortality. We identified a case group of 15,035 patients with chronic stroke (mean [SD] age of 53.25 [19.74] years; 55.63% male) who restarted aspirin use 4 weeks after suffering from TBI and a control group of 60,140 patients with chronic stroke (mean [SD] age of 53.12 [19.22] years; 55.63% male) who discontinued aspirin use after suffering from TBI. The risk of hospitalization of secondary ischemic stroke [adjusted hazard ratio (aHR) 0.694; 95% confidence interval (CI) 0.621–0.756; P < 0.001] and hemorrhagic stroke (aHR 0.642; 95% CI 0.549–0.723; P < 0.001) and all-cause mortality (aHR 0.840; 95% CI 0.720–0.946; P < 0.001) significantly decreased in patients with chronic stroke restarting aspirin use 1 month after suffering from TBI events (including intracranial hemorrhage) in comparison with the control subjects, regardless of those with or without diabetes mellitus, chronic kidney disease, myocardial infarction, atrial fibrillation, clopidogrel use, and dipyridamole use. Restarting aspirin use could lower the risks of secondary stroke (ischemic and hemorrhagic) hospitalization and all-cause mortality in patients with chronic stroke 1 month after suffering from TBI episodes.

Selectively compromised inner retina function following hypoxic-ischemic encephalopathy in mice: A noninvasive measure of severity of the injury.

The intricate system of connections between the eye and the brain implies that there are common pathways for the eye and brain that get activated following injury. Hypoxia-ischemia (HI) related encephalopathy is a consequence of brain injury caused by oxygen and blood flow deprivation that may result in visual disturbances and neurodevelopmental disorders in surviving neonates. We have previously shown that the tyrosine receptor kinase B (TrkB) agonist/modulator improves neuronal survival and long-term neuroprotection in a sexually differential way. In this study, we tested the hypotheses that; 1) TrkB agonist therapy improves the visual function in a sexually differential way; 2) Visual function detected by electroretinogram (ERG) correlates with severity of brain injury detected by magnetic resonance (MRI) imaging following neonatal HI in mice. To test our hypotheses, we used C57/BL6 mice at postnatal day (P) 9 and subjected them to either Vannucci's rodent model of neonatal HI or sham surgery. ERG was performed at P 30, 60, and 90. MRI was performed following the completion of the ERG. ERG in these mice showed that the a-wave is normal, but the b-wave amplitude is severely abnormal, reducing the b/a wave amplitude ratio. Inner retina function was found to be perturbed as we detected severely attenuated oscillatory potential after HI. No sex differences were detected in the injury and severity pattern to the retina as well as in response to 7,8-DHF therapy. Strong correlations were detected between the percent change in b/a ratio and percent hemispheric/hippocampal tissue loss obtained by MRI, suggesting that ERG is a valuable noninvasive tool that can predict the long-term severity of brain injury.

The alteration of serum bile acid profile among traumatic brain injury patients: a small-scale prospective study.

Traumatic brain injury is one of the major causes of morbidity and mortality worldwide. With the development of bile acids as a potential treatment, to identify the influence of traumatic brain injury on bile acid metabolism shows growing importance. This present study did a preliminary exploration of the bile acid profile alteration among traumatic brain injury patients. In total, 14 patients and 7 healthy volunteers were enrolled. The bile acid profile of the blood samples were detected by an Ultra-performance Liquid Chromatography Mass Spectrometer/Mass Spectrometer system. It was found that 6 bile acids were statistically decreased in traumatic brain injury patients comparing with healthy volunteers: glycocholic acid (median level 44.4 ng/ml vs 98.7 ng/ml, p = 0.003), taurocholic acid (median level 10.9 ng/ml vs 19.5 ng/ml, p = 0.006), glycoursodeoxycholic acid (median level 17.4 ng/ml vs 71.4 ng/ml, p = 0.001), ursodeoxycholic acid (median level <1 ng/ml vs 32.4 ng/ml, p = 0.002), taurochenodeoxycholic acid (median level <1 ng/ml vs 53.6 ng/ml, p = 0.003) and glycochenodeoxycholic acid (GCDCA, median level 160 ng/ml vs 364 ng/ml, p<0.001). In conclusion, traumatic brain injury events are able to induce bile acid metabolism alteration in plasma and might cause reduction in glycocholic, taurocholic, glycoursodeoxycholic, ursodeoxycholic, taurochenodeoxycholic and glycochenodeoxycholic acid levels.

507: PLASMA BIOMARKERS AS PROGNOSTICATION IN PATIENTS RECEIVING EXTRACORPOREAL MEMBRANE OXYGENATION

Introduction: Neurological complications in VA-ECMO beget a 7-15% mortality rate; however, existing literature demonstrates that neuromonitoring reduces the rate of complications. There is an increasing need for easily measured, accurate markers that can predict neurological injury. We propose that plasma biomarkers such as Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light Chain (NFL), and Tau can be utilized for prognostication of neurologic outcomes on ECMO. We hypothesised that patients with higher levels of inflammatory biomarkers will be at higher risk for neurologic complications. Methods: In this pilot prospective, cohort study, patients were consented within 24 hours of cannulation and followed over duration of VA-ECMO course. Peak concentrations of plasma biomarkers were used for analysis. Samples were taken daily for first 7 days and every other day afterwards as long as patient remained in the ICU. Outcomes were determined by the modified Rankin Scale (mRS) with a favorable outcome of mRS < 4. Statistical analyses used STATA v17 to calculate the Area Under ROC curves to determine sensitivity and specificity. Results: 20 patients were enrolled. Median age was 48.5 (41.5-62 IQR) yrs, and patients were 55% female. The median peak concentration values of GFAP, NFL, and Tau were 382.3 pg/ml (100.8-5,516.4), 8,306.7 pg/ml (2,338.9-13,577.2), and 1,278.4 pg/ml (318.7-3,447.4), respectively. There were 15 patients (75%) with unfavourable neurologic outcome at discharge, 17 patients had acute brain injury (85%), 10 patients had thromboembolic events (50%), and 14 patients had hemorrhagic events (70%). In prognostication of acute brain injury in patients, the plasma biomarkers GFAP, NFL and Tau achieved an AUC of 0.84, 0.73, and 0.73 respectively. Furthermore, GFAP, NFL and Tau achieved an AUC of 0.70, 0.81, and 0.70 for prediction of hemorrhagic events on ECMO. Conclusions: We identify three key plasma biomarkers, GFAP, NFL and Tau, that have the groundbreaking potential to assist prognostication of acute brain injury and hemorrhagic events on ECMO. We strongly recommend further research to identify feasibility and utility of novel biomarkers in the context of VA-ECMO and neurological complications to understand which combination of plasma biomarkers has the highest clinical yield.

A Fiber-Optic Sensor-Embedded and Machine Learning Assisted Smart Helmet for Multi-Variable Blunt Force Impact Sensing in Real Time

Early on-site diagnosis of mild traumatic brain injury (mTBI) will provide the best guidance for clinical practice. However, existing methods and sensors cannot provide sufficiently detailed physical information related to the blunt force impact. In the present work, a smart helmet with a single embedded fiber Bragg grating (FBG) sensor is developed, which can monitor complex blunt force impact events in real time under both wired and wireless modes. The transient oscillatory signal "fingerprint" can specifically reflect the impact-caused physical deformation of the local helmet structure. By combination with machine learning algorithms, the unknown transient impact can be recognized quickly and accurately in terms of impact magnitude, direction, and latitude. Optimization of the training dataset was also validated, and the boosted ML models, such as the S-SVM+ and S-IBK+, are able to predict accurately with complex databases. Thus, the ML-FBG smart helmet system developed by this work may become a crucial intervention alternative during a traumatic brain injury event.

Sex-Specific Human, Agent, and Environment-Related Interactions in Traumatic Brain Injury: Utility of The Haddon Matrix

<h3>Research Objectives</h3> To explore sex differences in the Host, the Agent, and the Environment utilizing computational analysis of traumatic brain injury (TBI) events. <h3>Design</h3> The retrospective population-based study utilized province-wide population-based decade-long health administrative data collected through the routine operation of the publicly funded health system in Ontario, Canada. <h3>Setting</h3> We used a previously established cohort of patients discharged between the fiscal years 2007/2008 and 2015/2016 from acute care and from the emergency department (ED) with diagnoses of TBI. <h3>Participants</h3> We drew upon health records of 235,003 unique patients (57% male) with TBI and the same number of reference patients without TBI, who were individually matched based on sex, age, place of residence, and income level, to organize factors associated with the TBI event. We dissected complex and multidimensional TBI event data by exploiting data mining and information visualization methods in male and female patients separately. We adopted concepts of the Haddon Matrix (Human, Agent, Environment) to organize injury event factors and compare TBI events of male and female patients. <h3>Interventions</h3> Not applicable. <h3>Main Outcome Measures</h3> Sex differences in the health status of the Host, the Agent, and the Environment at the TBI event phase. <h3>Results</h3> Based on perceived similarities, the computational technique detected 35 injury event-related factors, allowing observation of a set of definable patterns within the Host, the Agent, and the Environment. We uncovered significant sex-based differences in Host, Agent, and Environment patterns. We found that the Host's health status is of great importance to injury severity, and the Agent and the Environment have implications for external causes of injury. <h3>Conclusions</h3> Study findings support the utility of computational data mining in examining patterns of information within the TBI event. <h3>Author(s) Disclosures</h3> Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health (NIH) under Award Number R21HD089106 and the National Institute Of Neurological Disorders And Stroke of the NIH under Award Number R01NS117921 and partially by Canada Research Chair Programs.

Mirror-Based Robotic Therapy for Ankle Recovery with a Serious Game: A Case Study with a Neurological Patient.

Neuromuscular disorders, such as foot drop, severely affect the locomotor function and walking independence after a brain injury event. Mirror-based robotic therapy (MRT) has been a promising rehabilitation strategy favouring upper limb muscle strength and motor control in the last years. However, there are still no studies validating this technique in lower limb experimental protocols. This paper presents an innovative visual and motor feedback strategy based on serious games and MRT modalities. Thus, a preliminary system validation with a healthy participant is performed. Moreover, the strategy's potential effects were investigated in a neurologic patient's short rehabilitation program. After six sessions, the results of the method favoured active ankle plantarflexion range of motion and muscle activation. Although the patient had a positive adaptation at the end of the game, it is necessary to improve the proposed strategy to enhance the robotic experience in the long term.

Clinical-Pathological Study on Expressions β-APP, GFAP, NFL, Spectrin II, CD68 to Verify Diffuse Axonal Injury Diagnosis, Grade and Survival Interval

Traumatic brain injury (TBI) is one of the leading causes of death worldwide, particularly in young people. Diffuse axonal injuries (DAI) are the result of strong rotational and translational forces on the brain parenchyma, leading to cerebral oedema and neuronal death. DAI is typically characterized by coma without focal lesions at presentation and is defined by localized axonal damage in multiple regions of the brain parenchyma, often causing impairment of cognitive and neuro-vegetative function. Following TBI, axonal degeneration has been identified as a progressive process that begins with the disruption of axonal transport, leading subsequently to axonal swelling, axonal ballooning, axonal retraction bulges, secondary disconnection and Wallerian degeneration. The objective of this paper is to report on a series of patients who have suffered fatal traumatic brain injury, in order to verify neurological outcomes in dynamics, relative to the time of injury, using antibodies for neurofilament (NFL), spectrin II, beta-amyloid (β-APP), glial fibrillary acidic protein (GFAP) and cluster of differentiation 68 (CD68). From the studied cases, a total of 50 cases were chosen, which formed two study groups. The first study group comprises 30 cases divided according to survival interval. The control group comprises 20 cases with no history of traumatic brain injury. Cardiovascular disease and history of stroke, cases suffering from loss of vital functions, a post-traumatic survival time of less than 15 min, autolysis and putrefaction were established as criteria for exclusion. Based on their expression, we tested for diagnosis and degree of DAI as a strong predictor of mortality. Immunoreactivity was significantly increased in the DAI group compared to the control group. The earliest changes were recorded for GFAP and CD68 immunolabeling, followed by β-APP, spectrin II and NFM. The most intense changes in immunostaining were recorded for spectrin II. Comparative analysis of brain apoptosis, reactive astrocytosis and inflammatory reaction using specific immunohistochemical markers can provide important information on diagnosis of DAI and prognosis, and may elucidate the timing of the traumatic event in traumatic brain injury.

Sex-specific analysis of traumatic brain injury events: applying computational and data visualization techniques to inform prevention and management

BackgroundThe interplay of host, agent, and environment implicated in traumatic brain injury (TBI) events is difficult to account for in hypothesis-driven research. Data-driven analysis of injury data can enable insight into injury events in novel ways. This research dissected complex and multidimensional data at the time of the TBI event by exploiting data mining and information visualization methods.MethodsWe drew upon population-based decade-long health administrative data collected through the routine operation of the publicly funded health system in Ontario, Canada. We applied a computational approach to categorize health records of 235,003 patients with TBI versus the same number of reference patients without TBI, individually matched based on sex, age, place of residence, and neighbourhood income quantile. We adopted the basic concepts of the Haddon Matrix (host, agent, environment) to organize emerging factors significantly related to TBI versus non-TBI events. To explore sex differences, the data of male and female patients with TBI were plotted on heatmaps and clustered using hierarchical clustering algorithms.ResultsBased on detected similarities, the computational technique yielded 34 factors on which individual TBI-event codes were loaded, allowing observation of a set of definable patterns within the host, the agent, and the environment. Differences in the patterns of host, agent and environment were found between male and female patients with TBI, which are currently not identified based on data from injury surveillance databases. The results were internally validated.ConclusionsThe study outlines novel areas for research relevant to TBI and offers insight into how computational and visual techniques can be applied to advance the understanding of TBI event. Results highlight unique aspects of sex differences of the host and agent at the injury event, as well as differences in exposure to adverse social and environmental circumstances, which can be a function of gender, aiding in future studies of injury prevention and gender-transformative care.

Development of a generic version of the multiple errands test for severe acquired brain injuries

Background Impairment of executive functions is a frequent and disabling consequence of brain injury. In 1991, Shallice and Burgess elaborated the Multiple Errand Test (MET) to assess everyday troubles associated with this impairment. Objective Our first aim was to create a generic version of MET (MET-G) readily adaptable to different settings and for retesting. The second aim was to validate the revised version to detect executive impairment in individuals with severe ABI. Methods An inter-professional team of experts in neurorehabilitation created a revised version of MET. Twenty-one patients with sABI (severe Acquired Brain Injury) and a control group of 20 neurologically healthy subjects, took part in the testing of MET-G. Results MET-G clearly distinguished people with sABI from healthy controls based on Total error score, task completion, and rule breaking. The test showed good inter-rater reliability and internal consistency. Conclusions The new, generic version of MET was able to differentiate adults with sABI from controls and proved to be a good tool for evaluating executive functions in these patients in daily-life contexts. Indications on how to adapt the test to different contexts and different scoring modalities are provided.

Forensic criteria for determining the time of diffuse axonal damage in the event of traumatic brain injury

Establishing the diagnostic criteria for diagnosing of brain diffuse axonal injury duration as a separate form of traumatic brain injury. The dynamics of structural and functional changes in the neuron-gliovascular module and neuroinflammatory response revealed at the light-optical level and their diagnostically significant morphological signs established as a result of a comprehensive study that can be considered as evidence-based criteria for the diffuse axonal brain damage duration.