RESUMO
BACKGROUND: Behavioral and neuropsychological functions are frequent long-term sequelae of severe traumatic brain injury (TBI). Neuropeptides, such as nerve growth factor (NGF), can enhance neurogenesis and improve cognitive functions after TBI, playing a pivotal role in neuroplasticity. A limited number of studies documented the safety and efficacy of intranasal NGF administration in children with severe TBI. CASE REPORT: A fourteen-year-old boy with a diffuse axonal injury secondary to severe TBI was treated with human-recombinant NGF administration. This patient underwent treatment with intranasal hr-NGF administration at a total dose of 50 gamma/kg, three times a day for seven consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. NGF administration improved radiologic functional assessment evaluated with positron emission tomography scan (PET) and single photon emission computed tomography (SPECT), with an important improvement in clinical conditions. Significant improvements were also observed, mainly in cognitive processes, memory, the planning of a communication strategy, execution skills, attention, and verbal expression. No side effects were reported. CONCLUSIONS: Additional studies are required to gain a deeper insight into this neurotrophin's neuroprotective function, but our findings reveal a potential efficacy of intranasal hr-NGF administration in enhancing cognitive and clinical outcomes among children with diffuse axonal injury after severe TBI.
Assuntos
Administração Intranasal , Lesões Encefálicas Traumáticas , Cognição , Fator de Crescimento Neural , Humanos , Masculino , Fator de Crescimento Neural/administração & dosagem , Fator de Crescimento Neural/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/complicações , Adolescente , Cognição/efeitos dos fármacos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
BACKGROUND: In 2009, Gary and colleagues reviewed prior research examining racial and ethnic differences in outcomes after traumatic brain injury (TBI). Over the past 15 years, advances in research and changes in the demographic composition of the United States warrant a comprehensive understanding of racial and ethnic disparities after TBI. OBJECTIVE: A systematic review will be conducted to examine racial and ethnic differences in TBI outcomes from 2009 to 2023. METHODS: Preliminary searches and study screening processes will identify relevant English-language articles published from January 2009 to December 2023 using the CINAHL, Gale OneFile, PsycINFO (Ovid), and PubMed electronic databases. Relevant articles will include quantitative or mixed method approaches, involve individuals with TBI or their caregivers, and compare 2 or more groups by race or ethnicity on post-TBI outcomes. Quality will be assessed using the Newcastle-Ottawa Scale. This systematic review protocol was developed following PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. Results will be summarized, and a subgroup analysis may be conducted based on demographics (eg, age, gender, or sex). RESULTS: We have already identified abstracts using the search strategy for all 4 of the included electronic databases. We recently updated the search and will begin abstract screening of the additional abstracts identified from the last search completed in January 2024. This systematic review is anticipated to be completed by fall 2024, and its findings will be disseminated to the scientific community, persons with TBI, caregivers, and the lay audience. CONCLUSIONS: This systematic review will advance our understanding regarding outcome disparities among minoritized individuals with TBI, examine progress over the past 15 years in minimizing barriers encountered by these racial and ethnic groups, and provide professionals with a roadmap illustrating existing gaps in rehabilitation care, making way for further development and implementation of evidence-based interventions to improve health equity in TBI outcomes. TRIAL REGISTRATION: PROSPERO CRD42023394529; https://tinyurl.com/53mtcz9b. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/58763.
Assuntos
Lesões Encefálicas Traumáticas , Revisões Sistemáticas como Assunto , Humanos , Lesões Encefálicas Traumáticas/etnologia , Estados Unidos/epidemiologia , Etnicidade , Disparidades em Assistência à Saúde/etnologiaRESUMO
Traumatic brain injury (TBI) is an acquired insult to the brain caused by an external mechanical force, potentially resulting in temporary or permanent impairment. Microglia, the resident immune cells of the central nervous system, are activated in response to TBI, participating in tissue repair process. However, the underlying epigenetic mechanisms in microglia during TBI remain poorly understood. ARID1A (AT-Rich Interaction Domain 1 A), a pivotal subunit of the multi-protein SWI/SNF chromatin remodeling complex, has received little attention in microglia, especially in the context of brain injury. In this study, we generated a Arid1a cKO mouse line to investigate the potential roles of ARID1A in microglia in response to TBI. We found that glial scar formation was exacerbated due to increased microglial migration and a heightened inflammatory response in Arid1a cKO mice following TBI. Mechanistically, loss of ARID1A led to an up-regulation of the chemokine CCL5 in microglia upon the injury, while the CCL5-neutralizing antibody reduced migration and inflammatory response of LPS-stimulated Arid1a cKO microglia. Importantly, administration of auraptene (AUR), an inhibitor of CCL5, repressed the microglial migration and inflammatory response, as well as the glial scar formation after TBI. These findings suggest that ARID1A is critical for microglial response to injury and that AUR has a therapeutic potential for the treatment of TBI.
Assuntos
Lesões Encefálicas Traumáticas , Quimiocina CCL5 , Proteínas de Ligação a DNA , Camundongos Knockout , Microglia , Fatores de Transcrição , Animais , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/genética , Microglia/metabolismo , Microglia/patologia , Quimiocina CCL5/metabolismo , Quimiocina CCL5/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Camundongos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Movimento Celular , Cicatriz/patologia , Cicatriz/metabolismo , Camundongos Endogâmicos C57BL , MasculinoRESUMO
Background Little is known about health literacy in traumatic brain injury (TBI) survivors. The aims of this study were to compare health literacy in individuals with TBI with that of a control group; to examine the association between health literacy in individuals with TBI and demographic, injury, and cognitive factors; and compare the relationship between health literacy and physical and mental health outcomes. Methods A cross-sectional observational study design was used. Adults (≥18years) were recruited from an outpatient research centre in Victoria, Australia. There were 209 participants with a complicated mild to severe TBI at least 1year previously (up to 30years 6months) and 206 control participants. Results Individuals with TBI did not have poorer health literacy than controls (IRR=1.31, P =0.102, CI95% [0.947, 1.812]). Further analysis could not be completed due to the highly skewed Health Literacy Assessment Using Talking Touchscreen Technology - Short Form (Health LiTT-SF) data. Conclusion Health literacy performance in individuals with TBI was not significantly different to controls. Premorbid education may provide a critical cognitive reserve upon which TBI survivors can draw to aid their health literacy. These findings are specific to the Health LiTT-SF measure only and require replication using more comprehensive health literacy measures in culturally diverse samples.
Assuntos
Lesões Encefálicas Traumáticas , Letramento em Saúde , Humanos , Lesões Encefálicas Traumáticas/psicologia , Masculino , Feminino , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Adulto Jovem , Idoso , VitóriaRESUMO
BACKGROUND: There has been little direct examination of how traumatic brain injury (TBI) affects the rate of neurodegeneration for individuals with Alzheimer's disease (AD). METHODS: The study examined 89 cognitively normal adults (65 with and 24 without prior TBI) and 65 with AD (16 with and 49 without prior TBI). Cortical thickness was quantified from T1-weighted MRI scans at baseline and follow-up (mean interval 33.4 months). Partial least squares analysis was used to evaluate the effects of AD and TBI history on the longitudinal change in cortical thickness. RESULTS: Significant group effects were identified throughout the frontal and temporal cortices. Comparison of the AD groups to their control cohorts showed greater relative atrophy for the AD cohort with prior TBI. CONCLUSION: These results indicate that a history of TBI exacerbates longitudinal declines in cortical thickness among AD patients, providing new insights into the shared pathomechanisms between these neurological conditions.
Assuntos
Doença de Alzheimer , Lesões Encefálicas Traumáticas , Imageamento por Ressonância Magnética , Humanos , Doença de Alzheimer/patologia , Doença de Alzheimer/diagnóstico por imagem , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Masculino , Feminino , Idoso , Estudos Longitudinais , Córtex Cerebral/patologia , Córtex Cerebral/diagnóstico por imagem , Atrofia , Pessoa de Meia-Idade , Espessura Cortical do Cérebro , Idoso de 80 Anos ou maisRESUMO
Traumatic brain injury (TBI) is a major cause of morbidity and mortality in Bangladesh and also worldwide. Secondary brain injury from progressive intracerebral hematoma, increasing cerebral edema, raised intracranial pressure and subsequent cerebral ischemia is the main cause for morbidity and mortality following TBI. Secondary brain injury is worsened by post-traumatic coagulopathy, which occurs in brain injured patients and is associated with increase in risk of death and morbidity. The antifibrinolytic agent tranexamic acid (TXA) reduces the hematoma expansion and demonstrated improved clinical outcome also reduced the mortality and morbidity. This was a randomized controlled trial (RCT) done in the Department of Neurosurgery, Dhaka Medical College and Hospital. Included patients were randomized to get either the intravenous tranexamic acid (Group A) or placebo (Group B) treatment based on a computer-generated code list (50 patients in each group) along with usual medical management for traumatic brain injury. The extent of contusion expansion (hematoma plus perihematomal oedema) as the primary outcome at 48 hour after admission and was measured by brain CT scan. The contusion and oedema volume were calculated both the times (on admission and after 48 hours). Glasgow coma scale (GCS) after 48 hours and Glasgow outcome scale (GOS) after 7 days were observed. In this study showed increase in hematoma volume in both groups (p<0.05). But the increased hematoma volume in the Group A was significantly less than that in the control group. The mean total hemorrhage expansion was (1.5±1.1) ml and (4.6±1.9) ml in the Group A and Group B, respectively. In Group A- 02(4.0%) patients required operation, whereas in Group B- 11(22.0%) patients required operation. The result was significant (p=0.023) between groups. Therefore use of tranexamic acid is associated with lesser hematoma volume progression. Mean GCS (after 48 hours), mean GOS (after 7 days) result were significantly better in Group A (p<0.001). This study concluded that tranexamic acid has beneficial effect on the patient with significant traumatic brain injury. Tranexamic acid helps in reduction of intracerebral progression of contusion and improvement of clinical outcomes in patients with TBI.
Assuntos
Antifibrinolíticos , Lesões Encefálicas Traumáticas , Hematoma , Ácido Tranexâmico , Humanos , Ácido Tranexâmico/uso terapêutico , Ácido Tranexâmico/administração & dosagem , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Masculino , Antifibrinolíticos/uso terapêutico , Antifibrinolíticos/administração & dosagem , Adulto , Feminino , Hematoma/tratamento farmacológico , Hematoma/etiologia , Pessoa de Meia-Idade , Escala de Coma de Glasgow , Progressão da Doença , Adulto Jovem , Adolescente , Resultado do TratamentoRESUMO
Traumatic brain injury (TBI) is a leading cause of death and disability globally as well as in Bangladesh; its incidences are growing with an increasing number of high-speed motor vehicles, more movement of the public and mechanization in industry. The aim of the study was to analyze the causes, risk factors and treatment outcomes of traumatic brain injuries in victims reported to emergency and casualty departments following intensive care with or without surgical intervention in a tertiary care hospital. This prospective type of observational study was conducted at the Neurosurgery ward of Rangpur Medical College Hospital, Bangladesh from March 2022 to February 2024. A total of 360 head injury patients with TBI were assessed with gender, age, cause, and type of trauma, Glasgow Coma Scale on admission, associated other injuries, time lapsed from trauma to hospitalization and care given. A total of 360 Cases (n=360) of TBI, male 273(n=273) and female 87(n=87) were included most common group was 16-30 years (45%) and Males (75.83%) victims were more than female (24.16%). Frequency percentage cause is RTA 190(52.7%) and intra-cranial injury (42.77%), Intra and extra-cranial injury 206(57.22%), pathophysiological cause (n=360), SDH 122(33.88%), EDH (28.33%), concussion (15.83%), cerebral contusion (14.16%), diffuse axonal injury (05%) and subarachnoid haemorrhage (2.77%). Traumatic brain injury was common among young adult males and RTA was the leading cause. Many factors influence the better outcome of TBI with reduced mortality and morbidity including the patient's age, the injury's severity, the time between TBI and the start of definitive treatment associated with other major injuries and facilities available for resuscitative care.
Assuntos
Lesões Encefálicas Traumáticas , Centros de Atenção Terciária , Humanos , Lesões Encefálicas Traumáticas/terapia , Lesões Encefálicas Traumáticas/epidemiologia , Lesões Encefálicas Traumáticas/mortalidade , Feminino , Masculino , Bangladesh/epidemiologia , Adulto , Adolescente , Centros de Atenção Terciária/estatística & dados numéricos , Estudos Prospectivos , Pessoa de Meia-Idade , Adulto Jovem , Criança , Pré-Escolar , Escala de Coma de Glasgow , Lactente , Idoso , Fatores de RiscoRESUMO
BACKGROUND: Basal cisternostomy (BC) is a surgical technique to reduce intracranial hypertension following moderate to severe traumatic brain injury (TBI). As the efficacy and safety of BC in patients with TBI has not been well-studied, we aim to summarize the published evidence on the effect of BC as an adjunct to decompressive hemicraniectomy (DHC) on clinical outcome following moderate to severe TBI. METHODS: A systematic literature review was carried out in PubMed/MEDLINE and EMBASE to identify studies evaluating BC as an adjunct to decompressive hemicraniectomy (DHC) in moderate to severe TBI. Random effects meta-analysis was performed to calculate summary effect estimates. RESULTS: Eight studies reporting on 1345 patients were included in the qualitative analysis, of which five (1206 patients) were considered for meta-analysis. Overall, study quality was low and clinical heterogeneity was high. Adjuvant BC (BC + DHC) compared to standalone DHC was associated with a reduction in the length of stay in the ICU (Mean difference [MD]: -3.25 days, 95% CI: -5.41 to -1.09 days, p = 0.003), significantly lower mean brain outward herniation (MD: -0.68 cm, 95% CI: -0.90 to -0.46 cm, p < 0.001), reduced odds of requiring osmotherapy (OR: 0.09, 95% CI: 0.02 to 0.41, p = 0.002) as well as decreased odds of mortality at discharge (OR 0.68, 95% CI: 0.4 to 0.96, p = 0.03). Adjuvant BC compared to DHC did not result in higher odds of a favourable neurological outcome (OR = 2.50, 95% CI: 0.95-6.55, p = 0.06) and did not affect mortality at final follow-up (OR: 0.80, 95% CI: 0.17 to 3.74, p = 0.77). CONCLUSION: There is insufficient data to demonstrate a potential beneficial effect of adjuvant BC. Despite some evidence for reduced mortality and length of stay, there is no effect on neurological outcome. However, these results need to be interpreted with caution as they carry a high risk of bias due to overall scarcity of published clinical data, technical variations, methodological differences, limited cohort sizes, and a considerable heterogeneity in study design and reported outcomes.
Assuntos
Lesões Encefálicas Traumáticas , Craniectomia Descompressiva , Humanos , Lesões Encefálicas Traumáticas/cirurgia , Craniectomia Descompressiva/métodos , Hipertensão Intracraniana/cirurgia , Hipertensão Intracraniana/etiologia , Resultado do TratamentoRESUMO
In the presented clinical observation of complex therapy of severe combined trauma: severe brain contusion, subarachnoid hemorrhage, closed fracture of the occipital bone, closed compression fracture of ThVI-ThVIII vertebral bodies, contusion of the lungs and kidneys, blunt abdominal trauma and closed fracture of both bones of the right leg in lower third with displacement) in a teenager after an accident, the need for dynamic introscopic examination of the patient is shown for timely detection of abnormalities in the state of brain structures and correction of treatment up to surgical intervention. The effectiveness of the inclusion of Cytoflavin in complex treatment regimens was noted in the form of positive dynamics of the clinical and introscopic picture. The results obtained may serve as a basis for further research.
Assuntos
Lesões Encefálicas Traumáticas , Fossa Craniana Posterior , Combinação de Medicamentos , Mononucleotídeo de Flavina , Inosina Difosfato , Humanos , Adolescente , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Masculino , Fossa Craniana Posterior/lesões , Fossa Craniana Posterior/diagnóstico por imagem , Mononucleotídeo de Flavina/uso terapêutico , Inosina Difosfato/uso terapêutico , Niacinamida/uso terapêutico , Succinatos/uso terapêutico , Resultado do Tratamento , Traumatismo MúltiploRESUMO
BACKGROUND: Brain MRI with volumetric quantification, MRI volumetry, can improve diagnostic delineation of patients with neurocognitive disorders by identifying brain atrophy that may not be evident on visual assessments. OBJECTIVE: To investigate diagnostic utility of MRI volumetry in traumatic brain injury (TBI), early-onset Alzheimer disease (EOAD), late-onset Alzheimer disease, and behavioral variant frontotemporal dementia (bvFTD). METHOD: We utilized 137 participants of TBI (n = 40), EOAD (n = 45), LOAD (n = 32), and bvFTD (n = 20). Participants had 3D T1 brain MRI imaging amendable to MRI volumetry. Scan volumes were analyzed with Neuroreader. One-way ANOVA compared brain volumes across diagnostic groups. Discriminant analysis was done with leave-one-out cross validation on Neuroreader metrics to determine diagnostic delineation across groups. RESULT: LOAD was the oldest compared to other groups (F = 27.5, p < .001). There were no statistically significant differences in sex (p = .58) with women comprising 54.7% of the entire cohort. EOAD and LOAD had the lowest Mini-Mental State Exam (MMSE) scores compared to TBI (p = .04 for EOAD and p = .01 for LOAD). LOAD had lowest hippocampal volumes (Left Hippocampus F = 13.1, Right Hippocampus F = 7.3, p < .001), low white matter volume in TBI (F = 5.9, p < .001), lower left parietal lobe volume in EOAD (F = 9.4, p < .001), and lower total gray matter volume in bvFTD (F = 32.8, p < .001) and caudate atrophy (F = 1737.5, p < .001). Areas under the curve ranged from 92.3 to 100%, sensitivity between 82.2 and 100%, specificity of 78.1-100%. TBI was the most accurately delineated diagnosis. Predictive features included caudate, frontal, parietal, temporal lobar and total white matter volumes. CONCLUSION: We identified the diagnostic utility of regional volumetric differences across multiple neurocognitive disorders. Brain MRI volumetry is widely available and can be applied in distinguishing these disorders.
Assuntos
Doença de Alzheimer , Lesões Encefálicas Traumáticas , Encéfalo , Demência Frontotemporal , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/patologia , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/patologia , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Adulto , Atrofia/patologia , Diagnóstico DiferencialRESUMO
The popularity of electric scooters (ES) during the last five years due to climate neutrality and public availability led to increased numbers in traffic accidents with significant injuries. This study was conducted to overview e-scooter related computed tomography (CT) positive traumatic brain injuries, exploring circumstances, clinical course, outcomes and possible relations to behavioral patterns. We retrospectively reviewed medical data of all patients treated in our center during the period 2019 to 2023, medical records were analysed and statistically processed. This review included 45 patients, 75.7% were males and median age was 40 years old. Patient numbers did not differ between weekdays, working days versus weekends and time of the day. Eighty percent of patients were injured from falling off the scooter, the rest were hit by another vehicle while riding. None of the patients were known using helmet, significant alcohol intoxication was found in 68.8% of cases. The most common traumatic intracranial features were subarachnoid hemorrhage (55.6%), followed by brain contusions (48.9%), epidural (26.7%), subdural (26.7%) hemorrhages. Age had a positive correlation with alcohol intoxication (r = 0.596, p = 0.007) and poor outcomes (r = 0.522, p = 0.004), also, men over 40 years old were more likely to undergo surgery (p = 0.024), meanwhile operated patients suffered more infections (p = 0.011) and more often ended with poor outcomes (p < 0.001).
Assuntos
Acidentes de Trânsito , Lesões Encefálicas Traumáticas , Tomografia Computadorizada por Raios X , Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Estudos Retrospectivos , Adulto Jovem , Idoso , Adolescente , Contusão Encefálica , Intoxicação Alcoólica/epidemiologiaRESUMO
Importance: Blood-based biomarkers may clarify underlying neuropathology and potentially assist in clinical management of adolescents with sport-related concussion (SRC). Objective: To investigate the association between SRC and plasma biomarkers in adolescents. Design, Setting, and Participants: Prospective cohort study in Canadian sport and clinic settings (Surveillance in High Schools and Community Sport to Reduce Concussions and Their Consequences study; September 2019 to November 2022). Participants were a convenience sample of 849 adolescent (ages 10-18 years) sport participants with blood samples. Data were analyzed from February to September 2023. Exposures: Blood collection and clinical testing preseason (uninjured) and post-SRC follow-ups (ie, ≤72 hours, 1 week, and biweekly until medical clearance to return to play [RTP]). Main Outcomes and Measures: Plasma glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase-L1 (UCH-L1), neurofilament light (NfL), and total tau (t-tau) were assayed. Group-level comparisons of biomarker levels were conducted between uninjured and post-SRC intervals (postinjury day [PID] 0-3, 4-10, 11-28, and >28) considering age and sex as modifiers. Secondary analyses explored associations between biomarker concentrations and clinical outcomes (Sport Concussion Assessment Tool, Fifth Edition [SCAT5] symptom scores and time to RTP). Results: This study included 1023 plasma specimens from 695 uninjured participants (467 male participants [67.2%]; median [IQR] age, 15.90 [15.13-16.84] years) and 154 participants with concussion (78 male participants [51.0%]; median [IQR] age, 16.12 [15.31-17.11] years). Acute (PID 0-3) differences relative to uninjured levels were found for GFAP (female participants: 17.8% increase; ß = 0.164; 95% CI, 0.064 to 0.263; P = .001; male participants: 17.1% increase; ß = 0.157; 95% CI, 0.086 to 0.229; P < .001), UCH-L1 (female participants: 43.4% increase; ß = 0.361; 95% CI, 0.125 to 0.596; P = .003), NfL (male participants: 19.0% increase; ß = 0.174; 95% CI, 0.087 to 0.261; P < .001), and t-tau (female participants: -22.9%; ß = -0.260; 95% CI, -0.391 to -0.130; P < .001; male participants: -18.4%; ß = -0.203; 95% CI, -0.300 to -0.106; P < .001). Differences were observed for all biomarkers at PID 4 to 10, 11 to 28, and greater than 28 compared with uninjured groups. GFAP, NfL, and t-tau were associated with SCAT5 symptom scores across several PID intervals. Higher GFAP after 28 days post-SRC was associated with earlier clearance to RTP (hazard ratio, 4.78; 95% CI, 1.59 to 14.31; P = .01). Male participants exhibited lower GFAP (-9.7%), but higher UCH-L1 (21.3%) compared with female participants. Age was associated with lower GFAP (-5.4% per year) and t-tau (-5.3% per year). Conclusions and Relevance: In this cohort study of 849 adolescents, plasma biomarkers differed between uninjured participants and those with concussions, supporting their continued use to understand concussion neuropathology. Age and sex are critical considerations as these biomarkers progress toward clinical validation.
Assuntos
Traumatismos em Atletas , Biomarcadores , Concussão Encefálica , Proteínas tau , Humanos , Adolescente , Masculino , Feminino , Biomarcadores/sangue , Concussão Encefálica/sangue , Concussão Encefálica/complicações , Estudos Prospectivos , Traumatismos em Atletas/sangue , Traumatismos em Atletas/complicações , Criança , Proteínas tau/sangue , Proteínas de Neurofilamentos/sangue , Ubiquitina Tiolesterase/sangue , Proteína Glial Fibrilar Ácida/sangue , Canadá , Lesões Encefálicas Traumáticas/sangueRESUMO
Global outcomes have been reported to be associated with cerebrovascular reactivity (CVR) in the acute phase following moderate and severe traumatic brain injury (TBI). The association of CVR in the acute and chronic phase of injury with patient-reported health-related quality of life metrics (HRQOL) metrics has never been explored. The aim of this study is to examine the association of CVR, as measured by the cerebral oxygen indices (COx and COx_a), in the acute and chronic phase following moderate and severe TBI, with patient reported HRQOL. In this prospective cohort study, performed in a Canadian quaternary care center, the association between continuous acute and chronic phase CVR with patient reported HRQOL outcomes following moderate and severe TBI was examined. The main outcomes of interest of this study were validated measures of patient-reported HRQOL over various domains as measured by both the 12-Item Short-Form Health Survey (SF-12) and a Quality of Life after Brain Injury (QOLIBRI) questionnaire. In the 29 subjects of this cohort, acute phase CVR was found to be significantly more active in those with a favorable Mental Component Summary (MCS) scores of the SF-12 at early follow-up when measured by COx (-0.015 [IQR: -0.067 to 0.032] vs 0.040 [IQR: 0.019 to 0.137] for Favorable first MCS vs Unfavorable respectively; Mann-Whitney U test p-value = 0.046) and COx_a (0.038 [IQR: 0.009 to 0.062] vs 0.112 [IQR: 0.065 to 0.167] for Favorable first MCS vs Unfavorable respectively; Mann-Whitney U test p-value = 0.014). Further, multivariable logistic regression analysis found acute phase COx and COx_a to improve model performance when predicting favorable versus unfavorable early MCS scores over established parameters such as age and measures of injury severity. Associations between outcomes and chronic phase CVR were limited, potentially due to short recording periods. This is the first ever pilot study to identify a relationship between acute phase CVR following moderate-to-severe TBI with mental and cognitive outcomes as experienced by patients. Given the small cohort, these findings will need to be confirmed in a larger multicenter study. This highlights the need for additional examination of the role dysfunctional CVR may play in mental and cognitive outcomes, as well as patient-reported outcomes more generally following TBI.
Assuntos
Lesões Encefálicas Traumáticas , Qualidade de Vida , Humanos , Lesões Encefálicas Traumáticas/psicologia , Lesões Encefálicas Traumáticas/fisiopatologia , Lesões Encefálicas Traumáticas/complicações , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Circulação Cerebrovascular , Inquéritos e Questionários , CanadáRESUMO
BACKGROUND: Invasive blood pressure measurement is the in-hospital gold standard to guide hemodynamic management and consecutively cerebral perfusion pressure in patients with traumatic brain injury (TBI). Its prehospital use is controversial since it may delay further care. The primary aim of this study was to test the hypothesis that patients with severe traumatic brain injury who receive prehospital arterial cannulation, compared to those with in-hospital cannulation, do not have a prolonged time between on-scene arrival and first computed tomography (CT) of the head by more than ten minutes. METHODS: This retrospective study included patients 18 years and older with isolated severe TBI and prehospital induction of emergency anaesthesia who received treatment in the resuscitation room of the University Hospital of Graz between January 1st, 2015, and December 31st, 2022. A Wilcoxon rank-sum test was used to test for non-inferiority (margin = ten minutes) of the time interval between on-scene arrival and first head CT. RESULTS: We included data of 181 patients in the final analysis. Prehospital arterial line insertion was performed in 87 patients (48%). Median (25-75th percentile) durations between on-scene arrival and first head CT were 73 (61-92) min for prehospital arterial cannulation and 75 (60-93) min for arterial cannulation in the resuscitation room. Prehospital arterial line insertion was significantly non-inferior within a margin of ten minutes with a median difference of 1 min (95% CI - 6 to 7, p = 0.003). CONCLUSION: Time-interval between on-scene arrival and first head CT in patients with isolated severe traumatic brain injury who received prehospital arterial cannulation was not prolonged compared to those with in-hospital cannulation. This supports early out-of-hospital arterial cannulation performed by experienced providers.
Assuntos
Lesões Encefálicas Traumáticas , Serviços Médicos de Emergência , Tomografia Computadorizada por Raios X , Humanos , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/terapia , Estudos Retrospectivos , Masculino , Feminino , Tomografia Computadorizada por Raios X/métodos , Serviços Médicos de Emergência/métodos , Pessoa de Meia-Idade , Adulto , Fatores de Tempo , Cateterismo Periférico/métodos , IdosoRESUMO
BACKGROUND: The burgeoning field of regenerative medicine has significantly advanced with recent findings on biotherapies using human platelet lysates (HPLs), derived from clinical-grade platelet concentrates (PCs), for treating brain disorders. These developments have opened new translational research avenues to explore the neuroprotective effects of platelet-extracellular vesicles (PEVs). Their potential in managing neurodegenerative conditions like traumatic brain injury (TBI) and Parkinson's disease (PD) warrants further exploration. We aimed here to characterize the composition of a PEV preparation isolated from platelet concentrate (PC) supernatant, and determine its neuroprotective potential and neurorestorative effects in cellular and animal models of TBI and PD. METHODS: We isolated PEVs from the supernatant of clinical-grade PC collected from healthy blood donors utilizing high-speed centrifugation. PEVs were characterized by biophysical, biochemical, microscopic, and LC-MS/MS proteomics methods to unveil biological functions. Their functionality was assessed in vitro using SH-SY5Y neuronal cells, LUHMES dopaminergic neurons, and BV-2 microglial cells, and in vivo by intranasal administration in a controlled cortical impact (CCI)-TBI model using 8-weeks-old male C57/BL6 mice, and in a PD model induced by MPTP in 5-month-old male C57/BL6 mice. RESULTS: PEVs varied in size from 50 to 350 nm, predominantly around 200 nm, with concentrations ranging between 1010 and 1011/mL. They expressed specific platelet membrane markers, exhibited a lipid bilayer by cryo-electron microscopy and, importantly, showed low expression of pro-coagulant phosphatidylserine. LC-MS/MS indicated a rich composition of trophic factors, including neurotrophins, anti-inflammatory agents, neurotransmitters, and antioxidants, unveiling their multifaceted biological functions. PEVs aided in the restoration of neuronal functions in SH-SY5Y cells and demonstrated remarkable neuroprotective capabilities against erastin-induced ferroptosis in dopaminergic neurons. In microglial cells, they promoted anti-inflammatory responses, particularly under inflammatory conditions. In vivo, intranasally delivered PEVs showed strong anti-inflammatory effects in a TBI mouse model and conserved tyrosine hydroxylase expression of dopaminergic neurons of the substantia nigra in a PD model, leading to improved motor function. CONCLUSIONS: The potential of PEV-based therapies in neuroprotection opens new therapeutic avenues for neurodegenerative disorders. The study advocates for clinical trials to establish the efficacy of PEV-based biotherapies in neuroregenerative medicine.
Assuntos
Plaquetas , Lesões Encefálicas Traumáticas , Vesículas Extracelulares , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores , Doença de Parkinson , Vesículas Extracelulares/metabolismo , Animais , Humanos , Lesões Encefálicas Traumáticas/metabolismo , Camundongos , Plaquetas/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Masculino , Doença de Parkinson/terapia , Administração Intranasal , Modelos Animais de DoençasRESUMO
Traumatic brain injury (TBI) results from sudden accidents, leading to brain damage, subsequent organ dysfunction, and potentially death. Despite extensive studies on rodent TBI models, there is still high variability in terms of target points, and this results in significantly different symptoms between models. In this study, we established a more concise and effective TBI mouse model, which included locomotor dysfunctions with increased apoptosis, based on the controlled cortical impact method. Behavioral tests, such as elevated body swing, rotarod, and cylinder tests were performed to assess the validity of our model. To investigate the underlying mechanisms of injury, we analyzed the expression of proteins associated with immune response and the apoptosis signaling pathway via western blotting analysis and immunohistochemistry. Upon TBI induction, the mouse subjects showed motor dysfunctions and asymmetric behavioral assessment. The expression of Bax gradually increased over time and reached its maximum 3 days post-surgery, and then declined. The expression of Mcl-1 showed a similar trend to Bax. Furthermore, the expression of caspase-3, ROCK1, and p53 were highly elevated by 3 days post-surgery and then declined by 7 days post-surgery. Importantly, immunohistochemistry revealed an immediate increase in the level of Bcl-2 at the lesion site upon TBI induction. Also, we found that the expression of neuronal markers, such as NeuN and MAP2, decreased after the surgery. Interestingly, the increase in NFH level was in line with the symptoms of TBI in humans. Collectively, our study demonstrated that the established TBI model induces motor dysfunction, hemorrhaging, infarctions, and apoptosis, closely resembling TBI in humans. Therefore, we predict that our model may be useful for developing effective treatment option for TBI.
Assuntos
Lesões Encefálicas Traumáticas , Modelos Animais de Doenças , Animais , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/fisiopatologia , Camundongos , Masculino , Apoptose , Fatores de Tempo , Camundongos Endogâmicos C57BL , Atividade MotoraRESUMO
INTRODUCTION: Studies suggest disparities in outcomes in minoritized children after severe traumatic brain injury. We aimed to evaluate for disparities in intracranial pressure-directed therapies and outcomes after pediatric severe traumatic brain injury. METHODS: We conducted a secondary analysis of the Approaches and Decisions for Acute Pediatric TBI (ADAPT) Trial, which enrolled pediatric severe traumatic brain injury patients (Glasgow Coma Scale score ≤8) with an intracranial pressure monitor from 2014 to 2018. Patients admitted outside of the United States were excluded. Patients were categorized by race and ethnicity (Hispanic, non-Hispanic Black, non-Hispanic White, and "Other"). We evaluated outcomes by assessing mortality and 3-month Glasgow Outcome Score-Extended for Pediatrics. Our analysis involved parametric and nonparametric testing. MAIN RESULTS: A total of 671 children were analyzed. Significant associations included older age in non-Hispanic White patients (P < .001), more surgical evacuations in "Other" (P < .001), and differences in discharge location (P = .040). The "other" cohort received hyperventilation less frequently (P = .046), although clinical status during Paco2 measurement was not known. There were no other significant differences in intracranial pressure-directed therapies. Hispanic ethnicity was associated with lower mortality (P = .004) but did not differ in unfavorable outcome (P = .810). Glasgow Outcome Score-Extended for Pediatrics was less likely to be collected for non-Hispanic Black patients (69%; P = .011). CONCLUSIONS: Our analysis suggests a general lack of disparities in intracranial pressure-directed therapies and outcomes in children after severe traumatic brain injury. Lower mortality in Hispanic patients without a concurrent decrease in unfavorable outcomes, and lower availability of Glasgow Outcome Score-Extended for Pediatrics score for non-Hispanic Black patients merit further investigation.