TBI Group Research Articles

Measurement invariance of physical, mental, and social health PROMIS measures across individuals with spinal cord injury and traumatic brain injury.

The present study tested the fit and comparability of the tripartite model of health (Physical Health, Mental Health, and Social Health) proposed by the NIH PROMIS for adults with SCI and TBI. Participants were 630 adults with spinal cord injury (SCI; n = 336) and traumatic brain injury (TBI; n = 294) who completed 8 PROMIS short forms. The Physical Health domain is composed of the Physical Function, Pain Interference, and Fatigue scales. The Mental Health domain included the Depression, Anxiety, and Anger scales. Social Health included the Social Emotional Support scale. Confirmatory factor analyses supported the tripartite model of health over a unifactorial model of health for both SCI and TBI groups. Measurement invariance testing indicated the tripartite model met the level of configural and metric invariance for TBI and SCI groups, suggesting comparable structure and factor loadings. Failure to meet the level of scalar invariance indicated unequal intercepts across groups. Physical Function was identified as the source of noninvariance, and a partial scalar invariance model permitting different Physical Function intercepts across conditions was supported. Consistent with theory, findings supported construct validity of the PROMIS tripartite structure of health composed of Physical, Mental, and Social Health. PROMIS measures appeared to tap domains of health consistent with what is accepted for SCI and TBI populations, although the measurement of Physical Function was not equivalent across groups. Findings support the utility of PROMIS broadly as well as the need for condition-optimized measurement.

Nationwide improvements in geriatric mortality due to traumatic brain injury in Japan

BackgroundTraumatic brain injury (TBI), both isolated and in combination with extracranial lesions, is a global health problem associated with high mortality. Among various risk factors for poor clinical outcomes, age is the most important independent predictor of mortality in patients with TBI. TBI-related mortality is expected to increase as the society ages. However, in a super-aged society such as Japan, little is known about the trend of TBI-related mortality among older adults. Herein, we assessed the nationwide trend of the incidence and clinical outcomes of geriatric patients with TBI in Japan using the national Japanese Trauma Data Bank (JTDB) registry.MethodsIn this retrospective cohort study, cases of TBI (aged ≥65 years) in hospitals registered with the JTDB database between January 2004 and December 2018 were included. In-hospital mortality was the primary outcome, and mortality in the emergency department was the secondary outcome. The odds ratios (ORs) and 95% confidence intervals (CIs) for in-hospital deaths with respect to 3-year periods were assessed using multivariable analysis after adjusting for potential confounders.ResultsThe main cause of TBI in older individuals was falls. The proportion of patients who died after hospitalization during the study period decreased markedly from 29.5% (194/657) during 2004–2006 to 14.2% (1309/9240) during 2016–2018 in the isolated TBI group (adjusted OR = 0.42, 95% CI: 0.33–0.53) and from 48.0% (119/248) during 2004–2006 to 21.7% (689/3172) during 2016–2018 in the multiple trauma group (adjusted OR = 0.32, 95% CI: 0.23–0.45). The adjusted ORs for the 3-year increment were 0.84 (95% CI: 0.81–0.88) and 0.78 (95% CI: 0.75–0.83) for the isolated TBI and multiple trauma groups, respectively.ConclusionsUsing the national JTDB registry, we demonstrated a nationwide reduction in TBI-related mortality. Our findings in the super-aged society of Japan may provide insight for the treatment of geriatric patients with TBI worldwide.

Molecular hydrogen alleviates lung injury after traumatic brain injury: Pyroptosis and apoptosis

BackgroundTraumatic brain injury (TBI)-induced acute lung injury (ALI) is a critical condition, and inflammation and apoptosis play essential roles. Molecular hydrogen (H2) exerts anti-inflammatory and anti-apoptotic effects. Our previous work has shown that 42% H2 can improve TBI. In the current study, we tested the hypothesis that inhalation of hydrogen (42% H2, 21% O2, balanced nitrogen) for 1 h per day can improve TBI-induced ALI. MethodsSprague-Dawley male rats were randomly divided into 3 groups. Except for the sham group (group S), rats were subjected to a fluid percussion injury (FPI) and the H2 treatment group were given inhaled hydrogen for 1 h per day. We evaluated the lung function, pyroptosis and apoptosis at 24 h, 48 h and 72 h. ResultsCompared with group S, the rats in the TBI group (group T) showed obvious pulmonary edema after a TBI. Inhalation of high-concentration hydrogen significantly improved the rats. During this process, rats had some tendency to heal on their own, and H2 also accelerated the self-healing process. Lung injury scores, oxygenation index and pulmonary edema were consistent. Compared with group S, the pyroptosis-related proteins Caspase-1, apoptosis-associated speck-like protein containing CARD (ASC) and Gasdermin-D (GSDM-D) in the lung tissues of the rats in group T were significantly increased after a TBI. In the H2 treatment group (group H), these proteins were significantly decreased. The levels of IL-1β and IL-18 were significantly increased after TBI while in group H were significantly decreased. At the same time, cleaved caspase-3 and BCL-2/Bax were also changed after H2 treatment. These demonstrates the powerful ameliorating effect of H2 on pyroptosis, apoptosis and systemic inflammation. However, rats also had tendency to heal on their own, and H2 also accelerated the self-healing process at the same time. ConclusionsH2 improves TBI-ALI, and the mechanism may be due to the decrease of both pyroptosis and apoptosis and the alleviation of inflammation. These findings provide a reference and evidence for the use of H2 in TBI-ALI patients in the intensive care unit (ICU).

Compounding Effects of Traumatic Brain Injury, Military Status, and Other Factors on Pittsburgh Sleep Quality Index: A Meta-analysis.

Traumatic brain injury (TBI) or concussion is a known risk factor for multiple adverse health outcomes, including disturbed sleep. Although prior studies show adverse effects of TBI on sleep quality, its compounding effect with other factors on sleep is unknown. This meta-analysis aimed to quantify the effects of TBI on subjective sleep quality in the context of military status and other demographic factors. A programmatic search of PubMed database from inception to June 2020 was conducted to identify studies that compared subjective sleep quality measured using Pittsburgh Sleep Quality Index (PSQI) in individuals with TBI relative to a control group. The meta-analysis included group-wise standard mean difference (SMD) and 95% CI. Pooled means and SDs were obtained for TBI and non-TBI groups with and without military service, and meta-regression was conducted to test for group effects. Exploratory analysis was performed to test for the effect of TBI, non-head injury, military status, sex, and age on sleep quality across studies. Twenty-six articles were included, resulting in a combined total of 5,366 individuals (2,387 TBI and 2,979 controls). Overall, individuals with TBI self-reported poorer sleep quality compared to controls (SMD = 0.63, 95% CI: 0.45 to 0.80). Subgroup analysis revealed differences in the overall effect of TBI on PSQI, with a large effect observed in the civilian subgroup (SMD: 0.80, 95% CI: 0.57 to 1.03) and a medium effect in the civilian subgroup with orthopedic injuries (SMD: 0.40, 95% CI: 0.13 to 0.65) and military/veteran subgroup (SMD: 0.43, 95% CI: 0.14 to 0.71). Exploratory analysis revealed that age and history of military service significantly impacted global PSQI scores. Poor sleep quality in TBI cohorts may be due to the influence of multiple factors. Military/veteran samples had poorer sleep quality compared to civilians even in the absence of TBI, possibly reflecting unique stressors associated with prior military experiences and the sequelae of these stressors or other physical and/or psychological traumas that combine to heightened vulnerability. These findings suggest that military service members and veterans with TBI are particularly at a higher risk of poor sleep and its associated adverse health outcomes. Additional research is needed to identify potential exposures that may further heighten vulnerability toward poorer sleep quality in those with TBI across both civilian and military/veteran populations.

Postural Stability Challenges in Narrow Walking after Traumatic Brain Injury

The aim of this study was to evaluate the predictability and complexity of gait under preferred and narrow walking conditions for groups of TBI and age matched control subjects in order to determine if non-linear measures may be appropriate for identifying gait deviations not detected with more routine techniques. Ten participants from each group walked at preferred gait and with a narrow base of support. Center of mass motion was calculated from marker motion recorded with motion capture. Measures of predictability and complexity of center of mass motion were calculated with Recurrence Quantification Analysis. Walking with a narrow base of support resulted in a less predictable center of mass motion (reduced %Determinism) for TBI and control groups (p=0.0019 and p=0.0008, respectively), but no difference was found between groups. For the TBI group, there was a significant decrease in complexity of center of mass motion (lower Entropy, p=0.0038) with narrow base of support compared to preferred walking, but no difference in Entropy was found between groups. These results suggest non-linear measures determined using techniques such as Recurrence Quantification Analysis might have potential to be valid and reliable measurement techniques for predicting gait deviations in future studies.

A-125 The Impact of Bilingualism on Symbol Digit Modalities Test Performance Following Traumatic Brain Injury

Abstract Objective Traumatic brain injury (TBI) survivors exhibit cognitive deficits. Research suggests that multilingualism can influence neurocognitive performance. We examined the effects of TBI and bilingualism/monolingualism on a test of attention and cognitive speed (i.e., Symbol Digit Modalities Test; SDMT). Method The sample consisted of 55 healthy comparison (27 Spanish-English bilinguals; 28 English-monolinguals), 34 acute TBI (14 Spanish-English bilinguals; 23 English-monolinguals), and 27 chronic TBI (13 Spanish-English bilinguals; 12 English-monolinguals) participants. Acute TBI participants were tested 6 months post-injury; chronic TBI participants were tested 12 months or more post-injury. A series of 3X2 ANOVAs were conducted to determine the effect of TBI and language on SDMT written and oral performance. Results ANOVAs revealed the healthy comparison group outperformed both TBI groups on SDMT written, p = 0.000, ηp2 = 0.21. Also, the healthy comparison and chronic TBI groups outperformed the acute TBI group on SDMT oral, p = 0.000, ηp2 = 0.13. Interaction effects emerged between TBI and bilingualism/monolingualism. On SDMT written and oral, acute TBI English-monolinguals outperformed acute TBI Spanish-English bilinguals; meanwhile, chronic TBI Spanish-English bilinguals outperformed chronic TBI English-monolinguals, p < 0.05, ηp2 = 0.09–0.10. Conclusion The acute TBI group performed worse than healthy comparison adults on both SDMT tasks. Furthermore, the chronic TBI group demonstrated better SDMT oral abilities compared to the acute TBI group. Relative to monolinguals with TBI, our findings suggest better cognitive recovery of attention and cognitive speed in bilingual TBI participants. Future studies with larger sample sizes should examine if learning English first or second impacts Spanish-English bilingual TBI survivors’ SDMT performance compared to English-monolingual TBI survivors.

A-94 Characterization of Million Veteran Program (MVP) Enrollees with Comprehensive TBI Evaluation (CTBIE) Data: An Analysis of Neurobehavioral Symptoms

Abstract Objective Using a large sample of U.S. Veterans enrolled in the Million Veteran Program (MVP), we sought to evaluate neurobehavioral symptoms obtained from the Veterans Health Administration’s Comprehensive Traumatic Brain Injury Evaluation (CTBIE). Method Eligible participants (N = 12,144) included MVP-enrolled Veterans who completed the CTBIE, a clinician-administered interview that assesses for historical, deployment-related TBIs and evaluates current symptoms using the Neurobehavioral Symptom Inventory (NSI). Clinicians completing the CTBIE made clinical determinations about each participant’s TBI diagnostic status (n = 7631 CTBIE+, n = 4513 CTBIE-) as well as likely symptom etiology (TBI: n = 612, Behavioral Health: n = 4965, Combination TBI and Behavioral Health [Comorbid]: n = 2773, Symptom Resolution; n = 750; and Other: n = 1282). We evaluated the association of TBI diagnostic group and symptom etiology group with neurobehavioral symptoms using ANCOVAs adjusted for sociodemographic characteristics. Results Results showed a significant effect of TBI on the NSI total score (p < 0.001, ηp2 = 0.02), with CTBIE+ Veterans endorsing greater symptoms than CTBIE- Veterans. There was also a significant association of symptom etiology group with the NSI total score (p < 0.001, ηp2 = 0.07). Post-hoc analyses showed that the Behavioral Health and Comorbid groups endorsed significantly greater symptoms compared to the TBI, Symptom Resolution, and Other groups. A similar pattern of results was found for all NSI symptom domain scores (vestibular, somatic, cognitive, and affective) and symptom breadth scores. Conclusions Findings from this large epidemiologic MVP study bolster prior work suggesting that behavioral health (e.g., depression, PTSD) greatly contributes to post-concussive symptom endorsement in chronic TBI. Results further highlight the importance of prioritizing mental health treatment in this vulnerable population.

Changes in Jail Admissions Before and After Traumatic Brain Injury

ObjectivesTraumatic brain injury (TBI) is differentially concentrated within incarcerated populations. Despite the consistency of this observation, the timing of within-individual changes in criminal justice contact in relation to TBI remains under-investigated. For example, previous studies have primarily considered TBI as a causal influence of later criminal justice contact. However, TBI may also serve as a consequence of criminal justice contact or a criminogenic lifestyle. The current study simultaneously observes both possibilities by examining criminal justice contact before, around the time of, and after the first reported TBI.MethodsDrawing from a combination of self-report and lifetime official record data from a jail cohort admitted between February 2017 and September 2017 and who sustained their first reported TBI at age 21 or older (N = 531), the current study examines jail admissions in the 24 months before and 24 months after the first reported TBI and across eight biannual intervals (N = 4,248 person-periods).ResultsAny and misdemeanor admissions slightly increased pre-TBI and continued to increase around the time of and following TBI, never returning to pre-TBI levels. Felony admissions remained stable around the time of injury and increased post-TBI. Further analyses that incorporated a comparison group revealed that these patterns are unique to the TBI group and not a result of a larger systematic process.ConclusionsThese findings indicate that the probability of jail admission is greatest post-TBI, but also increases leading up to sustaining a TBI.

DTI-derived parameters differ between moderate and severe traumatic brain injury and its association with psychiatric scores.

Diffusion tensor imaging (DTI) parameters in the corpus callosum have been suggested to be a biomarker for prognostic outcomes in individuals with diffuse axonal injury (DAI). However, differences between the DTI parameters on moderate and severe trauma in DAI over time are still unclear. A secondary goal was to study the association between the changes in the DTI parameters, anxiety, and depressive scores in DAI over time. Twenty subjects were recruited from a neurological outpatient clinic and evaluated at 2, 6, and 12months after the brain injury and compared to matched age and sex healthy controls regarding the DTI parameters in the corpus callosum. State-Trace Anxiety Inventory and Beck Depression Inventory were used to assess psychiatric outcomes in the TBI group over time. Differences were observed in the fractional anisotropy and mean diffusivity of the genu, body, and splenium of the corpus callosum between DAI and controls (p < 0.02). Differences in both parameters in the genu of the corpus callosum were also detected between patients with moderate and severe DAI (p < 0.05). There was an increase in the mean diffusivity values and the fractional anisotropy decrease in the DAI group over time (p < 0.02). There was no significant correlation between changes in the fractional anisotropy and mean diffusivity across the study and psychiatric outcomes in DAI. DTI parameters, specifically the mean diffusivity in the corpus callosum, may provide reliable characterization and quantification of differences determined by the brain injury severity. No correlation was observed with DAI parameters and the psychiatric outcome scores.

Long-Term Outcomes of Total Body Irradiation Plus Cyclophosphamide Versus Busulfan Plus Cyclophosphamide As Conditioning Regimen for Acute Lymphoblastic Leukemia: A Comparative Study

Introduction: Total body irradiation-Cyclophosphamide (TBI-Cy) and Busulfan-Cyclophosphamide (Bu-Cy) are the most commonly used conditioning regimens in allogeneic hematopoietic stem cell transplantation (allo-HCT) for acute lymphoblastic leukemia (ALL). TBI-based conditioning regimens may have a better antitumor effect at sanctuary cites compared to chemotherapy regimens. However, some controversy still remains concerning the role of TBI in adult ALL. Therefore, we aimed to retrospectively investigate long-term treatment outcomes of ALL patients post allo-HCT and identify prognostic factors and the impact of the conditioning.Methods: We enrolled consecutive patients with ALL who underwent alloHCT from 1990 to 2016 in our center, following a TBI- or a Busulfan (Bu)-based conditioning regimen. TBI at 14.4Gy was divided at 6 fractions over 3 days and Bu (mainly oral) at 4mg/kg/day. Both regimens included 120mg/kg Cy. Graft source was mainly mobilized peripheral blood stem cells.Results: We studied 151 ALL (114 B-ALL, 35 T-ALL and 2 biphenotypic) patients aged 28±12 years, transplanted in CR1 (60), other CR (33) or relapsed/refractory disease (58) from sibling (87), HLA matched (42) or mis-matched (17) unrelated and alternative donors (5). TBI-based conditioning was administered in 84, whereas non-TBI in 67. No differences were observed in baseline characteristics, except for disease phase, disease risk index (DRI) and graft source. The majority of non-TBI patients had relapsed/refractory disease at transplant (50.7% versus 28.6% in TBI-conditioning, p=0.043) and subsequently significantly higher DRI (p=0.025). Furthermore, bone marrow was the graft source in significantly higher number of non-TBI patients (28.4% versus 8.3% in the TBI group, p=0.001).With a follow-up of 19.0 (0.5-170.5) in TBI and 14.5 (1.2-319.1) months in the non-TBI group, there was no difference in the incidence of acute (Grade 2-4) or chronic GVHD, thrombotic microangiopathy, bacterial or fungal infections. Only viral infections were significantly increased in the non-TBI group (59% versus 41% in the TBI group, p=0.03). Therefore, there was no significant difference in the cumulative incidence (CI) of treatment-related mortality (5-year CI of 24.1% in non-TBI versus 27.7% in the TBI group, p=0.678) or relapse mortality (5-year CI of 29.2% in non-TBI versus 37.1% in the TBI group, p=0.283).Overall survival (OS) was similar in the TBI and non-TBI group (5-year 46.7% compared to 35.8%, p=0.201). In the multivariate analysis, unfavorable pre-transplant predictors of OS were age (p=0.024), higher disease risk index (DRI) (p=0.007) and female to male donor (p=0.006). Disease-free survival (DFS) was similar in the TBI and non-TBI group (5-year 47.1% compared to 35.4%, p=0.134), with age, higher DRI and female to male donor being unfavorable predictors. When the analysis was limited to patients transplanted in CR1 (40 in the TBI versus 20 in the non-TBI group), there were also no significant differences.Interestingly, age predicted OS and DFS only in the TBI group. TBI patients younger than 40 years had significantly high OS (55.1%, p=0.023) and DFS (55.5%, p=0.02) versus the older ones. Older TBI patients had higher TRM (43.3% versus 20.1%, p=0.135) and relapse mortality (45.8 versus 24.7, p=0.238) that did not reach levels of statistical significance. However, the same was not true for the non-TBI group (p=0.233 for DFS, p=0.326 for OS).Conclusion: In our retrospective data of the last 3 decades, the type of conditioning regimen did not influence the outcome of transplantation. Based on our results, high dose TBI is a feasible conditioning in terms of a prolonged DFS and OS for younger patients and seems an efficient tool to cure high-risk ALL in CR1. It should be kept in mind that intravenous BU is also used with stable pharmacokinetics. Since our data were not powered to appraise superiority of one regimen in terms of efficacy and toxicity, the choice between TBI or Bu conditioning regimens is still under consideration. Treatment is complex for adult ALL patients and remains a field of debate and a challenge for prospective studies in the future. DisclosuresGavriilaki:European Hematology Association: Research Funding.

Non-TBI Based Conditioning Regimen in Peripheral Blood Stem Cell Transplantation (PBSCT) for Adult Acute Lymphoblastic Leukemia Patients: A Single Center Experience

Introduction: The outcome of adult acute lymphoblastic leukemia (ALL) patients with chemotherapy only is not promising and overall survival (OS) does not exceed 30%. Allogeneic Hematopoietic Stem Cell transplantation (allo-HSCT) in first or beyond complete remission (≥CR1) has shown a superior OS rate of approximately 50 % over conventional chemotherapy protocols. Total body irradiation plus Cyclophosphamide (TBI/Cy) and oral busulfan plus cyclophosphamide (BU/Cy) are commonly used myeloablative conditioning regimens in ALL. TBI-based conditioning regimen is considered the standard of care.Aim: To compare the outcomes of allo HSCT using TBI/Cy and BU/Cy conditioning regimens in adult standard and high risk ALL patients in ≥CR1.Material and methods: We retrospectively analyzed the outcome of TBI/Cy and BU/Cy myeloablative conditioning regimen (MAC). BU/Cy cohort included 33 patients (9 females & 24 males) with a median age of 28 years (19-42). Myeloablative BU oral dose was 16mg/kg/4 days & Cy dose was 120 mg/kg IV over 4 days. TBI/Cy cohort included 45 patients (14 females & 31 males) with a median age of 24 years (19-46). TBI dose was 12 Gy fractionated for 5 days & Cy dose was 120mg/kg IV over 4 days. Both cohorts underwent allo-PBSCT at Nasser Institute Hospital, Cairo, between 1997-2010 (TBI group) and 2010-2017 (BU group) (Table1). All patients received graft-versus-host disease (GVHD) prophylaxis using cyclosporine-A (3mg/kg/day IV) from day -1 and methotrexate (15 mg/m2 IV) on day + 1 then 10 mg/m2 IV on days +3, +6 and +11. Post-transplant neutrophil and platelet engraftment were defined by three successive days with absolute neutrophilic count >=1x 109/L and platelet count >=20 x 109/L (without transfusion).Results:In the TBI arm, median time to neutrophil and platelet engraftment was 15 days (9-22) and 15 days (7-47), respectively vs. 14 days (10-22) and 12 days (10-21), respectively in the BU arm. 11/45 TBI patients (24.4 %) developed grade ≥2 acute-GVHD vs. 7/33 (21.2%) patients in the BU arm. Extensive cGVHD was reported in 8/45 (17.7 %) TBI arm vs. 6/33 (18%) patients in the BU arm. Limited cGVHD occurred in 5/45 (11.1%) TBI patients vs. 3/33 (9%) in the BU arm. Cumulative survival was 42.2 % and 15 months OS was 36.7% in the TBI arm vs. 63.6 % and 51.3 % in the BU arm (p= 0.02) (Figure 1). The incidence of sepsis and aGVHD as a cause of transplant related mortality (TRM) were significantly higher in the TBI arm vs. BU arm (p<0.001) (Table 2).Conclusions: Preliminary data demonstrates thatoutcome of BU/Cy is comparable to TBI/Cy as MAC regimen for Allo SCT inadult ALL. With limitation of resources, standard and high risk ALL patients may benefit from allo PBSCT using irradiation-free conditioning regimen associated with lower incidence of sepsis and aGVHD as a cause of transplant related mortality. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Cognitive Outcomes in Children with Mild Traumatic Brain Injury: An Examination Using the National Institutes of Health Toolbox Cognition Battery.

This study is the first to examine cognitive outcomes after pediatric mild TBI using the National Institutes of Health Toolbox Cognition Battery (NIHTB-CB), a computerized cognitive test battery. The NIHTB-CB includes two complex measures of attention and executive function that allow differentiation of accuracy and response speed. We compared performance on the NIHTB-CB among children 8-16 years of age with mild TBI (n = 143) versus children with orthopedic injuries (OIs; n = 74) recruited in emergency departments and followed for 6 months post-injury. Mixed-model analyses showed that the mild TBI group showed significantly lower Fluid Cognition composite scores than the OI group at 10 days (group intercept, p = 0.018); the magnitude of group differences declined modestly over time (group × time interaction, p = 0.055). Effect sizes were d = 0.34 at 10 days post-injury, d = 0.27 at 3 months, and d = 0.10 at 6 months. No significant effects of group or time were found for the Crystallized Cognition composite. Analyses of Fluid Cognition subtests indicated that children with mild TBI displayed deficits for as long as 3 months on measures of attention and executive function (e.g., cognitive flexibility, inhibitory control), but not on measures of explicit memory, working memory, or processing speed. The poorer performance of the mild TBI group on measures of attention and executive function was attributable largely to slowed reaction time, not decreased accuracy. The findings suggest that children with mild TBI demonstrate persistent deficits in fluid cognition that are most apparent on tasks that combine demands for both speed and executive function.

Potentiating Hemorrhage in a Periadolescent Rat Model of Closed-Head Traumatic Brain Injury Worsens Hyperexcitability but Not Behavioral Deficits.

Post-traumatic epilepsy (PTE) and neurocognitive deficits are devastating sequelae of head injuries that are common in adolescents. Investigating desperately needed treatments is hindered by the difficulties in inducing PTE in rodents and the lack of established immature rat models of pediatric PTE. Hemorrhage is a significant risk factor for PTE, but compared to humans, rats are less prone to bleeding because of their rapid blood coagulation system. In this study, we promoted bleeding in the controlled cortical impact (CCI) closed-head injury model with a 20 min pre-impact 600 IU/kg intraperitoneal heparin injection in postnatal day 35 (P35) periadolescent rats, given the preponderance of such injuries in this age group. Temporo-parietal CCI was performed post-heparin (HTBI group) or post-saline (TBI group). Controls were subjected to sham procedures following heparin or saline administration. Continuous long-term EEG monitoring was performed for 3 months post-CCI. Sensorimotor testing, the Morris water maze, and a modified active avoidance test were conducted between P80 and P100. Glial fibrillary acidic protein (GFAP) levels and neuronal damage were also assessed. Compared to TBI rats, HTBI rats had persistently higher EEG spiking and increased hippocampal GFAP levels (p < 0.05). No sensorimotor deficits were detected in any group. Compared to controls, both HTBI and TBI groups had a long-term hippocampal neuronal loss (p < 0.05), as well as contextual and visuospatial learning deficits (p < 0.05). The hippocampal astrogliosis and EEG spiking detected in all rats subjected to our hemorrhage-promoting procedure suggest the emergence of hyperexcitable networks and pave the way to a periadolescent PTE rat model.

Antibody-Free Mass Spectrometry Identification of Vascular Integrity Markers in Major Trauma.

Antibody mediated strategies for protein biomarker detection are common, but may limit discovery. We hypothesized that the use of antibody-free proteomics is feasible for detecting protein biomarkers in plasma of patients sustaining major trauma. A subset of subjects with major trauma from a prospective observational trial were analyzed. Patients were assigned to one of four groups based on their presenting Abbreviated Injury Severity Score (AIS). Sensitive, antibody-free selective reaction monitoring (SRM) mass spectrometry (MS), with spiked-in isotopically labeled synthetic peptides, was used for targeted protein quantification of a panel of 10 prospective targets. An overall tiered sensitivity analytical approach was used for peptide detection and quantification based upon plasma immunoaffinity depletion and PRISM fractionation. Forty-four patients were included in the analysis, of which 82% were men with a mean age of 50 (±19) years. Half had isolated head injury (n = 22), with the remaining patients experiencing multiple injuries or polytrauma (n = 14), isolated body injury (n = 2), or minor injury (n = 6). Peptides from 3 proteins (vascular adhesion molecule 1 [VCAM1], intercellular adhesion molecule 1 [ICAM1], and matrix metalloproteinase 9 [MMP9]) were detected and quantified in non-depleted processed plasma. Peptides from 2 proteins (angiopoietin 2 [Ang2] and plasminogen activator inhibitor-1 [PAI1]) were detected and quantification in depleted plasma, whereas the remaining 5 of the 10 prospective targets were undetected. VCAM1 (p = 0.02) and MMP9 (p = 0.03) were significantly upregulated in in the major trauma groups (1–3) versus mild injury group (4), whereas the others were not. There were no differences in protein expression between patients with traumatic brain injury (TBI; groups 1 and 2) versus those without TBI (groups 3 and 4). We detected non-specific upregulation of proteins reflecting blood–brain barrier breakdown in severely injured patients, indicating label-free MS techniques are feasible and may be informative.

A Serosurvey of Tick-Borne Encephalitis Virus in Sweden: Different Populations and Geographical Locations.

Background: New risk areas for tick-borne encephalitis (TBE) are emerging and the spread of disease and vaccine coverage is unclear in Sweden. We wanted to study the prevalence and levels of TBE-virus (TBEV) antibodies in southern Sweden, and to investigate whether there were individuals with undiagnosed TBE. Materials and Methods: Two cohorts of sera were collected: One group of anonymous individuals in rural areas (AIRA) in Skåne and one group of volunteers who often got tick-bites (tick-bitten individuals [TBI]). An enzyme-linked immunosorbent assay for TBEV IgM and IgG was performed, as well as a TBEV neutralization test (NT) in selected individuals. Results: In the AIRA group, there was an IgG seropositivity of 5.3%. There were individuals with high antibody levels both in areas previously considered as risk areas (Bromölla and Knislinge), as well as in another area (Tyringe). In the TBI group, 45% of the individuals were vaccinated according to the questionnaires and IgG seropositivity was 28%. A lower seroprevalence and levels of antibodies were seen in the middle-aged group (50-69 years) compared with younger or elderly study participants. A positive NT revealed several individuals with suspected undiagnosed episodes of TBE. Conclusion: Subclinical or misdiagnosed cases have probably occurred in Skåne. Middle-aged individuals had lower levels of IgG, which could indicate either less tick exposure or a lower vaccine response. Less than half of the TBI were vaccinated, an indication that more information about the disease and vaccine might be needed. We conclude that the study motivates an increased awareness of TBEV in the region.

Arousing Effects of Electroacupuncture on the "Shuigou Point" in Rats with Disorder of Consciousness after Traumatic Brain Injury.

Orexin is an important neuropeptide that stimulates cortical activation and arousal and is involved in the regulation of wakefulness and arousal. Our previous meta-analysis showed that acupuncture fared well in the treatment of TBI-induced DOC in which “shuigou (DU 26)” was the most important and frequent point targeted. In the present study, we investigated whether electroacupuncture (EA) promotes TBI-induced unconsciousness wakefulness via orexin pathway. A TBI rat model was established using a control cortical impact (CCI) model. In the stimulated group, TBI rats received EA (15 Hz, 1.0 mA, 15 min). In the antagonist group, TBI rats were intraperitoneally injected with the orexin receptor 1 (OX1R) antagonist SB334867 and received EA. Unconsciousness time was observed in each group after TBI, and electrocorticography (ECoG) was applied to detect rats' EEG activity. Immunohistochemistry, enzyme-linked immunosorbent assay, and western blot were used to assess the levels of orexin-1(OX1) and OX1R expression in the mPFC. We show that duration of unconsciousness and the ratio of delta power in ECoG in the EA group were significantly reduced compared with those in the TBI group. EA could increase OX1 and OX1R expression in the mPFC and reduced the loss of orexin-producing neurons in LHA. However, all the efficacy of EA was blocked by the OX1R antagonist SB334867. Our findings suggest that EA promotes the recovery of consciousness of TBI-induced unconscious rats via upregulation of OX1and OX1R expression in mPFC.

Optimization of Mouse Model of Aplastic Anemia Induced by Pan T Lymphocytes Combined with Irradiation

To establish the acquired aplastic anemia mouse model through the X-ray irradiation in combination with lymphocytes injection. AA Group: the purified Pan T lymphocytes from the spleen of C57BL/6J mice were enriched and injected to the mice through tail vein(5×106), the CB6F1 mice were exposed to 3,4 and 5 Gy X-ray irradiation; TBI Group: the CB6F1 mice were exposed to 3,4 and 5 Gy X-ray irradiation, and were injected with the same volume of PBS buffer; Control group: the CB6F1 mice were only injected with the same volume of PBS buffer. The peripheral blood routine was examined and the number of nucleated cells in bone marrow were calculated；the hematopoiesis changes in bone marrow was examined；flow cytometry was used to examine the distribution of T lymphocytes in bone marrow, and it also used to examine the apoptosis of bone marrow cells and the differentiation of spleen T lymphocytes. Compared with 4, 5 Gy irradiated mice in AA groups, the survival time of 3 Gy irradiated AA groups was significantly prolonged. 3, 4 and 5 Gy X-ray irradiation combined with Pan T lymphocyte injection could successfully induced severe reduction of red blood cells, blood neutrophils, and platelets, severe reduction of bone marrow nucleated cells, severe bone marrow hematopoietic failure, and the significant expansion of T lymphocytes ratio in the bone marrow. CD4+ and CD8+ T cells were both increased, but mainly on CD8+ T cells, and could promote the differentiation of T cells from naïve T cells to effector memory T cells. 3, 4 and 5 Gy X-ray irradiation combined with 5×106 pan-T cell injection could successfully induce acquired aplastic anemia through T lymphocyte hyperfunction. Compared with 4, 5 Gy irradiated AA group, the 3 Gy irradiated AA group shows significantly longer survival time, and the peripheral blood routine profile closely resembles the clinical manifestations of AA patients.

Therapeutic effects of eugenol in a rat model of traumatic brain injury: A behavioral, biochemical, and histological study

Background and aimTraumatic brain injury (TBI) results in death or long term functional disabilities. Eugenol is demonstrated to be beneficial in a range of experimental models of neurological disorders via its anti-inflammatory and antioxidant properties. Thus, the present study was designed to investigate the neuroprotective effects of eugenol in a weight-drop induced rat model of TBI. Experimental procedureRats were assigned into five groups; control and TBI groups pretreated with vehicle, and three TBI groups pretreated with different doses of eugenol (25, 50, and 100 mg/kg/day, p.o., seven consecutive days). Except for the control, all other groups were subjected to TBI using Marmarou’s weight-drop method. 24 h after TBI, locomotor functions and short term memory were evaluated. Lastly animals were scarified and the estimation of lipid peroxidation in brain tissue, blood-brain barrier (BBB) integrity, brain water content (brain edema) and histopathology of the brain tissue were performed. ResultsWeight-drop induced TBI caused functional disabilities in the rats as indicated by impairment in locomotor activities and short term memory. The TBI also resulted in augmented neuronal cell death designated by chromatolysis. The results also showed disruption in the BBB integrity, increased edema, and lipid peroxidation in the brain of the rats exposed to trauma. Pretreatment with eugenol (100 mg/kg) ameliorated histopathological, neurochemical, and behavioral consequences of trauma. ConclusionFor the first time this study revealed that eugenol can be considered as a potential candidate for managing the functional disabilities associated with TBI because of its antioxidant activities.

Decreased serum uric acid in patients with traumatic brain injury or after cerebral tumor surgery.

Objectives:To investigate changes in sUA in patients with TBI or patients after cerebral tumor surgery and the possible mechanism of these changes.Methods:This prospective cohort study enrolled patients with TBI or underwent cerebral tumor surgery at West China Hospital, China, from November 2014 to May 2018. Serum UA (sUA) levels, urine excretion, UA oxidant product allantoin and other clinical parameters were assessed.Results:100 patients were enrolled for analysis. sUA in patients with TBI or underwent cerebral tumor surgery started to decline from day 1 after injury or surgery compared to control. This decreasing trend continued from day 3 (143.2±59.3 μmol/L, 188.8±49.4 μmol/L vs 287.3±80.2 μmol/L, p<0.0001) until day 7. No difference in urinary UA excretion was found in the TBI group or cerebral tumor surgery group. Urine allantoin and the allantoin to sUA ratio of the TBI group decreased on day 3 compared with the control group. The structural equation model showed that the sUA level was related to the Glasgow coma score (GCS) (r=0.5383, p<0.0001), suggesting the potential association of UA with consciousness level, as well as serum protein and electrolytes including albumin, calcium and phosphate.Conclusion:The sUA was decreased in patients with TBI or underwent cerebral tumor surgery.

Evaluation of diffusion measurements reveals radial diffusivity indicative of microstructural damage following acute, mild traumatic brain injury

PurposeMild TBI, characterized by microstructural damage, often undetectable on conventional imaging techniques, is a pervasive condition that disturbs brain function and can potentially result in long-term deficits. Deciphering the underlying microstructural damage in mild TBI is crucial for establishing a reliable diagnosis and enabling effective therapeutics. Efforts to capture this damage have been extensive, but results have been inconsistent and incomplete. MethodsTo that effect, we set out to examine the shape of the diffusion tensor in mild TBI during the acute phase of injury. We inspected diffusivity and geometric measurements describing the diffusion tensor's shape and compared mild TBI (N = 34, 20.4–66.6 yo) measurements with those from healthy control (N = 42, 20.7–67.2 yo) participants using voxelwise tract-based spatial statistics. Subsequently, to explore associations between the diffusion measurements in mild TBI, we performed nonparametric statistics and machine learning techniques. ResultsOverall, mild TBI displayed a diffuse increase in Dλ2, Dλ3, Dradial, Dmean, and Cspherical, with a diffuse decrease in Afractional, Amode, and Clinear, in addition to no change in Daxial or Cplanar. Most notably, our results provide evidence for Dradial as a potential biomarker for microstructural damage, specifically its main component Dλ2, based on their performance in discriminating between mild TBI and control groups. Afractional was also found to be important for discriminating between groups. ConclusionOur results revealed the importance of a diffusion measurement often overlooked, Dradial, in assessing TBI and suggest differentiating diffusion measurements has the potential utility to detect variations in the underlying pathophysiology after injury.