Research on the dynamic changes of neurological dysfunction and cognitive function impairment in traumatic brain injury / 解剖学报

Objective To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI). Methods Totally 60 12⁃month⁃old Balb/ c mice were divided into control group (10 in group) and TBI group (50 in group). TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting. Results Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium⁃binding adapter molecule 1(IBA1), chemokine C⁃X3⁃C⁃motif ligand1 (CX3CL1), C⁃X3⁃C chemokine receptor 1(CX3CR1), NOD⁃like receptor thermal protein domain associated protein 3 (NLRP3), and phosphorylation nuclear factor(p⁃NF)⁃κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin⁃6(IL⁃6) and tumor necrosis factor⁃α(TNF⁃α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p⁃Tau protein in the model group continued to increase at all time. Conclusion The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.

Recent progress of targeting Nrf2-ferroptosis to treat brain injury after ischemic stroke / 中国临床药理学与治疗学

Emerging evidences suggest that ferroptosis plays a vital role in the pathophysiological process of brain injury after Ischemic stroke. Accumulating evidence supports pharmacological inhibition of ferroptosis as a therapeutic target for brain injury after Ischemic stroke through activating nuclear factor erythroid 2-related factor 2 (Nrf2), which transcriptionally controls many key components of the ferroptosis pathway. In this review, briefly describe ferroptosis processes and the roles they play in contributing to brain injury after ischemic stroke in the brain. We then provide a critical overview of the relationship between Nrf2 signalling and ferroptosis. With a focus on discuss how therapeutic modulation of the Nrf2 pathway is a viable strategy to explore in the treatment of ferroptosis-driven brain injury after Ischemic stroke.

Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice / 神经科学通报·英文版

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.

Processamento auditivo central e questionário de autopercepção pós-treinamento auditivo acusticamente controlado em indivíduos com traumatismo cranioencefálico leve / Central auditory processing and self-perception questionnaire after acoustically controlled auditory training in individuals with mild traumatic brain injury

RESUMO Objetivo Correlacionar os resultados da avaliação comportamental do processamento auditivo central e do questionário de autopercepção após o treinamento auditivo acusticamente controlado. Método Foram avaliados dez indivíduos com média de idade de 44,5 anos, que sofreram traumatismo cranioencefálico de grau leve. Os indivíduos foram submetidos a avaliação comportamental do processamento auditivo central e também responderam ao questionário de autopercepção "Treinamento Auditivo Formal" após a intervenção terapêutica. O questionário foi composto por questões referentes a percepção auditiva, compreensão de ordens, solicitação de repetição de enunciados, ocorrência mal-entendidos, tempo de atenção, desempenho auditivo em ambiente ruidoso, comunicação ao telefone e autoestima e os pacientes foram solicitados a assinalar a frequência de ocorrência dos comportamentos listados. Resultados As habilidades auditivas de figura-fundo e memória para sons em sequência e processamento temporal correlacionaram-se com melhora para seguir instruções, diminuição das solicitações de repetições e aumento do tempo de atenção e melhora da comunicação e da compreensão ao telefone e para assistir TV. Conclusão Observou-se adequação das habilidades auditivas de fechamento auditivo, figura fundo, e processamento temporal na avaliação pós-treinamento auditivo acusticamente controlado, além de redução das queixas quanto ao comportamento auditivo.

ABSTRACT Purpose To correlate behavioral assessment results of central auditory processing and the self-perception questionnaire after acoustically controlled auditory training. Methods The study assessed 10 individuals with a mean age of 44.5 years who had suffered mild traumatic brain injury. They underwent behavioral assessment of central auditory processing and answered the Formal Auditory Training self-perception questionnaire after the therapeutic intervention - whose questions address auditory perception, understanding orders, request to repeat statements, occurrence of misunderstandings, attention span, auditory performance in noisy environments, telephone communication, and self-esteem. Patients were asked to indicate the frequency with which the listed behaviors occurred. Results Figure-ground, sequential memory for sounds, and temporal processing correlated with improvement in following instructions, fewer requests to repeat statements, increased attention span, improved communication, and understanding on the phone and when watching TV. Conclusion Auditory closure, figure-ground, and temporal processing had improved in the assessment after the acoustically controlled auditory training, and there were fewer auditory behavior complaints.

Calcitonin gene-related peptide inhibits neuronal apoptosis in heatstroke rats via PKA/p-CREB pathway / 中华创伤杂志(英文版)

PURPOSE@#The incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway.@*METHODS@#We established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant.@*RESULTS@#Electroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F = 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F = 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F = 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F = 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F = 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F = 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression.@*CONCLUSIONS@#CGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.

Research progress on mechanism of traumatic brain injury promoting fracture healing / 中国修复重建外科杂志

OBJECTIVE@#To summarize the research progress on the mechanism related to traumatic brain injury (TBI) to promote fracture healing, and to provide theoretical basis for clinical treatment of fracture non-union.@*METHODS@#The research literature on TBI to promote fracture healing at home and abroad was reviewed, the role of TBI in fracture healing was summarized from three aspects of nerves, body fluids, and immunity, to explore new ideas for the treatment of fracture non-union.@*RESULTS@#Numerous studies have shown that fracture healing is faster in patients with fracture combined with TBI than in patients with simple fracture. It is found that the expression of various cytokines and hormones in the body fluids of patients with fracture and TBI is significantly higher than that of patients with simple fracture, and the neurofactors released by the nervous system reaches the fracture site through the damaged blood-brain barrier, and the chemotaxis and aggregation of inflammatory cells and inflammatory factors at the fracture end of patients with combined TBI also differs significantly from those of patients with simple fracture. A complex network of humoral, neural, and immunomodulatory networks together promote regeneration of blood vessels at the fracture site, osteoblasts differentiation, and inhibition of osteoclasts activity.@*CONCLUSION@#TBI promotes fracture healing through a complex network of neural, humoral, and immunomodulatory, and can treat fracture non-union by intervening in the perifracture microenvironment.

Adult human neural cells in culture following traumatic brain injury

Objective: The present study aims to evaluate the viability of adult human neural cells in culture obtained from traumatized brain tissues collected in emergency surgery procedures. Methods: Exploratory, descriptive, quantitative and cross-sectional study evaluating samples obtained from patients who underwent traumatic brain injury with extrusion of brain tissue submitted to cell culture in a standardized medium, being preserved during 168h. After observation under phase contrast microscopy and immunohistochemical processing for neuronal (MAP-2) and glial (GFAP) markers, morphometric parameters of neural cells (cell body area, dendritic field length and fractal dimension) were evaluated using ImageJ software, with data obtained after 24, 72 and 168h being compared using non-parametric Kruskal Wallis test, followed by Dunn's post hoc test. Results: The explant of the nervous tissue revealed a consolidated pattern of cell migration into the culture medium. Cell proliferation, upon reaching confluence, presented an aspect of cellular distribution juxtaposed along the culture medium at all time points analyzed. Both neurons and glial cells remained viable after 168h in culture, with their morphologies not varying significantly throughout the time points evaluated. Immunohistochemistry for MAP-2 showed a relatively well-preserved cytoskeletal organization. GFAP immunoreactivity revealed activated astrocytes especially at the later time point. Conclusions: Our results point out the viability of cell culture from traumatized human nervous tissue, opening up perspectives for the use of substances of natural origin that may contribute neuroprotectively to neuronal maintenance in culture, allowing future translational approach.

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.

Introdução: traumatismo cranioencefálico é um problema global de saúde pública devido à sua gravidade e altas taxas de morbimortalidade em todo o mundo. Identificar preditores associados ao aumento da mortalidade e desfechos funcionais desfavoráveis após o evento do traumatismo craniencefálico é primordial para minimizar as taxas de morbidade e mortalidade. Portanto, este estudo tem como objetivo estabelecer um protocolo para investigar os preditores de mortalidade e recuperação funcional após traumatismo cranioencefálico grave no Brasil. Métodos: este estudo tem como objetivo investigar os preditores de mortalidade e recuperação funcional em pacientes com traumatismo cranioencefálico, além de fornecer uma visão geral do traumatismo cranioencefálico no estado do Espírito Santo. O estudo abrangerá todos os pacientes internados por traumatismo cranioencefálico grave (Escala de Coma de Glasgow ≤ 8) no Hospital Estadual de Urgência e Emergência, o hospital de referência para traumas no Espírito Santo. Os desfechos de interesse incluem mortalidade hospitalar e recuperação funcional após 24 meses da alta hospitalar. Os participantes serão acompanhados em setenta e duas horas, três meses, seis meses, doze meses e vinte e quatro meses após o trauma. A morbidade será determinada pela avaliação de: 1) nível de incapacidade motora e cognitiva, 2) comprometimento funcional e qualidade de vida, e 3) aspectos do tratamento e reabilitação. Além disso, a carga de traumatismo cranioencefálico, estimada em anos de vida perdidos, será calculada. Discussão: os resultados deste estudo ajudarão a identificar variáveis que podem predizer a morbidade e a mortalidade após traumatismo cranioencefálico grave. Além disso, as descobertas terão implicações práticas para: 1) o desenvolvimento de políticas públicas, 2) investimentos em infraestrutura hospitalar e 3) compreensão do impacto socioeconômico da perda funcional nesses indivíduos. Registro do estudo: o estudo recebeu aprovação do Comitê de Ética da Universidade Federal do Espírito Santo sob o número de protocolo 4.222.002 em 18 de agosto de 2020

Septic complications in patients of traumatic brain injury: An impact on clinical and functional outcome

Background: Septic complications in traumatic brain injury causes short- and long-term cerebral dysregulation by disruption of blood brain barrier, reduced brain perfusion, neuroinflammation and deposition of amyloid. Materials and methods: The present study attempted to observe patients of traumatic brain injury for the development of septic complications during the hospital stay. 89 patients were included in the study with different grades of brain injury (Injury Severity Score (ISS) range, 9-72). The patients were managed according to the trauma protocol and classified into 3 groups based on the severity of trauma (ISS 9-17 (moderate), 18-30 (severe), and >32 (most severe)). The patients were observed for the development of major septic complications during the course of their hospital stay, which impacted on the morbidity and mortality while determining the clinical and functional outcome at the end. Results: Mean age of the study population was 33.5 years. TBI was more common in younger age groups with severe grades of injury, those with multiplicity of head injuries, sepsis with a pulmonary focus, prolonged ICU and in-hospital stay together with high mortality. Septic complications were also more common in cases with higher grades of TBI and more prolonged hospital stay. Patients requiring intubation had a higher risk of developing infectious complications. 69 patients (77.5%) required intubation and mechanical ventilation. Pneumonia was the most common source of sepsis leading to the respiratory failure while the most common cause being aspiration at the time of injury Genitourinary complications were also common leading to urosepsis. Most common organisms isolated were Staphylococcus aureus, Acinetobacter, klebsiella and Pseudomonas. Conclusion: Traumatic brain injury (TBI) when complicated by sepsis and multi organ failure increases the mortality and morbidity with less favorable clinical and functional outcome together with increased duration of ICU and hospital stay.

Adverse drug reaction profile of patients taking amantadine for traumatic brain injury in a tertiary care hospital

Background: Amantadine is found to be effective for the treatment of complications associated with traumatic brain injury. Drug-related side effects are common with Amantadine especially when combined with other drugs. Comprehensive information about the incidence and severity of these adverse effects is not available. Aim and Objectives: The aim of the study was to analyze the pattern of occurrence of adverse drug reactions (ADRs) in patients receiving Amantadine for traumatic brain injury in a tertiary care hospital. We also assessed the causality, severity and preventability of ADRs. Materials and Methods: This prospective cohort study was conducted among patients taking Amantadine for a continuous period of 1 month for traumatic brain injury in neurosurgery department between June 2020 and December 2020. Tools used were ADR Reporting form of National Pharmacovigilance Centre, WHO causality scale, Hartwig and Siegel scale, and Schumock and Thornton scale. Descriptive statistics were used and the values were expressed in numbers and percentages. Results: ADRs were experienced in 55 patients (36.7%) out of 150 patients and all the patients were on combination therapy. ADR was present more in male patients (63.6%) compared to females (36.4%). The most common ADRs were headache, ankle edema and dry mouth. Majority of ADRs belonged to the possible category according to the WHO causality assessment scale. Majority of the ADRs (61.9%) were mild level 1 according to severity scale. All the ADRs came under the definitely or probably preventable category. Conclusion: ADRs with Amantadine are common but mild and preventable.

Teoría de la Mente en pacientes Traumatizados Craneoencefálico

Antecedentes: Uno de los impedimentos más importantes en los traumatismos craneoencefálicos (TEC), revistan en las dificultades de interacción social, la Teoría de la Mente (ToM) es un factor fundamental de la cognición social, que permite una interacción satisfactoria del sujeto. Objetivo: Observar la capacidad de ToM en pacientes TEC moderado o severo, y su relación con dominios neurocognitivos. Método: Pacientes diagnosticados con TEC moderado o severo, evaluados neuropsicológicamente, edad 16 y 45 años, se aplicaron Test de la Mirada (TdlM) e Historias Extrañas (HT). Resultados: Se encontraron correlaciones entre TdlM y HT con memoria y funciones ejecutivas. Pacientes lesionados izquierdos, rinden significativamenie menos en HT. Conclusiones: Pacientes con TEC moderado o grave tienen una disminución de la capacidad de ToM. Existe una relación entre memoria episódica y ToM, podría deberse a que esta última requiere información a experiencias pasadas. Durante la infancia la ToM depende de la memoria episódica, pero cuando ambas se desarrollan adecuadamente, son independientes. Existe una relación entre funciones ejecutivas y ToM. Ambos constructos están vinculados en la infancia, pero luego comienzan a ser más independientes. Sin embargo, la ToM igualmente va a requerir de las funciones ejecutivas.

Background: One of the most important impediments in traumatic brain injuries (TBI), are the difficulties of social and family interaction. The Theory of Mind (ToM) is a fundamental factor of social cognition, which allows a satisfactory interaction of the individual with his environment. Objetive: To observe the ability of ToM in moderate or severe TBI patients, and its relationship with neurocognitive domains. Methods: Outpatients with diagnosis of moderate or severe TBI, evaluated neuropsychologically, age between 16 and 45 years, were applied Eyes Test (ET) and the Hinting task (HT). Results: Correlations were found between ET and HT with memory and executive functions. Injured left, perform significantly less in HT Patients with moderate or severe TBI have a decrease in ToM capacity. Conclusions: There is a relationship between episodic memory and ToM, which could be due to the latter 's need to request information from past experiences through episodic memory. During childhood ToM depends on episodic memory, but when both are achieved and developed properly, they are independent. There is a relationship between executive functions and ToM. Both constructs are linked in childhood, but then they begin to be more independent. However, ToM tasks will also require executive functions.

Feature Deconstruction Strategy Based Identification of Acute Features Associated With Impairment of Activities of Daily Living in Patients With Traumatic Brain Injury / 中山大学学报(医学科学版)

ObjectiveTo identify acute phase features associated with the prognosis of traumatic brain injury （TBI）. MethodsThrough two traditional strategies， correlation analysis and prediction model， and one innovative research strategy based on feature deconstruction， a retrospective analysis was conducted using demographic， acute phase and chronic phase features of 354 TBI patients to identify acute phase features associated with activities of daily living （ADL） in chronic phase of TBI. For feature deconstruction strategy， the LASSO （Least Absolute Shrinkage and Selection Operator） algorithm was used to build a prediction model that could effectively predict ADL based on non-ADL chronic phase features. The model could indicate the key chronic phase dimensions determining the ADL in TBI patients. We then identified demographic and acute phase variables that were significantly associated with these key chronic phase features. ResultsThe feature deconstruction strategy revealed that ADL could be deconstructed into chronic phase dimensions such as weak limbs in TBI population. Importantly， to the best of our knowledge， this strategy revealed for the first time the association of these important acute phase features with specific chronic phase impairment features. For example， TBI patients had a higher risk for chronic phase recent memory impairment if they had a prolonged coma time and low GCS scores at acute phase ［scaled coma time OR95%CI = 94.288 （35.095， 273.231）； scaled GCS OR95%CI = 0.068 （0.030， 0.147）］； the patients had a higher risk for insight impairment and disorientation at chronic phase if they had hydrocephalus at acute phase ［insight impairment OR95%CI = 6.760 （3.653，12.855） ； disorientation OR95%CI = 6.538 （3.530， 12.490）］. All strategies showed that the strongest risk factors for ADL damage in the chronic phase included prolonged coma time and low GCS scores as well as hydrocephalus. ConclusionThis study provides an innovative research strategy to establish the association between acute injury features and chronic recovery features， and to identify demographic and acute phase features associated with the prognosis of TBI.

Research Progress of Radiation-induced Brain Injury for Nasopharyngeal Carcinoma / 肿瘤防治研究

Radiation-induced brain injury (RBI) is a common long-term complication of radiotherapy for nasopharyngeal carcinoma (NPC) and seriously affects the quality of life and overall survival of patients. In the era of intensity-modulated radiation therapy (IMRT), the long-term complications after radiotherapy, especially RBI, are becoming increasingly concerning because a number of treated patients with NPC obtain long-term survival. At present, the understanding of RBI is still being explored, and its pathogenesis and treatment methods are continuously updated. This article reviews the research progress of RBI in patients with NPC.

The Mechanism of Brain Injury Induced by Rotational Motion / 医用生物力学

Traumatic brain injury ( TBI ) has caused serious economic and social burdens, but due to its heterogeneity, there is no effective treatment. In TBI with different severity, diffuse axonal injury (DAI) incidenceis high. The investigation on DAI will contribute to the diagnosis and treatment of TBI. In this study, the classification of TBI and the research status of DAI were summarized. The method to judge the severity of TBI and DAI, and animal experimental models and related injury criteria and thresholds were reviewed. The result show that DAI is mainly generated by rotational acceleration and it is related to angular acceleration, angular velocity and duration. Several TBI animal models can induce the pathology of DAI, and inertial rotation models which can produce only rotational acceleration have been developed. However, these models are instantaneous rotation models, and the rotation duration is uncontrollable, thus a longer duration is impossible, and DAI severity under long rotational motion cannot be studied. The study proposes that a new rotation animal model which can control rotation duration should be developed. The development of the animal model and investigation on pathomechanism of the model will contribute to the prevention and treatment of DAI.

Effects of scutellarin on neuroinflammation in rats with traumatic brain injury by regulating cGAS/STING signaling pathway / 中国药房

OBJECTIVE To investigate the improvement effects and mechanism of scutellarin （Scu） on neuroinflammation in rats with traumatic brain injury （TBI）. METHODS The modified Feeney method was applied to construct TBI rat model. The rats were randomly grouped into TBI group，Scu low-dose group （40 mg/kg），Scu high-dose group （80 mg/kg），cyclic guanylate- adenylate synthase （cGAS） inhibitor group （cGAS inhibitor RU.521，450 μg/kg），with 24 rats in each group. Other 24 rats were included in the sham operation group. The modified neurological deficit score （mNSS） method was applied to assess the neurological function of rats； the brain water content of rats was measured by dry/wet specific gravity method； hematoxylin-eosin and TdT-mediated dUTP nick-end labeling staining were applied to observe the pathological changes and apoptosis of brain tissue in rats； the levels of interferon-β （IFN-β），CXC chemokine ligand-10 （CXCL10），tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rat brain tissue were detected by enzyme-linked immunosorbent assay； Western blot method was applied to detect the expression of cGAS/interferon gene stimulating protein （STING） signal pathway-related proteins in brain tissue of rats. RESULTS Compared with the sham operation group，the mNSS，brain water content，apoptosis rate，the contents of IFN-β，CXCL10，TNF-α and IL-6，and the relative expressions of cGAS and STING proteins in TBI group increased significantly （P＜0.05）； there were edema，bleeding and pathological damage to neurons in the brain tissue. Compared with TBI group，the above indicators and pathological changes of rats in administration groups were improved significantly （P＜0.05），and the effect of Scu was in a dose- dependent manner （P＜0.05）； however，there was no statistically obvious difference in the above indicators between the Scu high- dose group and the cGAS inhibitor group （P＞0.05）. CONCLUSIONS Scu may alleviate neuroinflammation，reduce brain tissue damage and apoptosis，and promote the recovery of neural function in TBI rats by inhibiting the activation of cGAS/STING signaling pathway.

Electroacupuncture in Treatment of Acute Gastrointestinal Injury in Patients with Severe Traumatic Brain Injury: A Multicenter Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate whether electroacupuncture (EA) would improve gastrointestinal function and clinical prognosis in patients with severe traumatic brain injury (TBI) complicocted by acute gastrointestinal injury (AGI).@*METHODS@#This multicenter, single-blind trial included patients with TBI and AGI admitted to 5 Chinese hospitals from September 2018 to December 2019. A total of 500 patients were randomized to the control or acupuncture groups using a random number table, 250 cases in each group. Patients in the control group received conventional treatment, including mannitol, nutritional support, epilepsy and infection prevention, and maintenance of water, electrolytes, and acid-base balance. While patients in the acupuncture group received EA intervention at bilateral Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Tianshu (ST 25), and Zhongwan (RN 12) acupoints in addition to the conventional treatment, 30 min per time, twice daily, for 7 d. The primary endpoint was 28-d mortality. The secondary endpoints were serum levels of D-lactic acid (D-lac), diamine oxidase (DAO), lipopolysaccharide (LPS), motilin (MTL) and gastrin (GAS), intra-abdominal pressure (IAP), bowel sounds, abdominal circumference, AGI grade, scores of gastrointestinal failure (GIF), Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and Multiple Organ Dysfunction Syndrome (MODS), mechanical ventilation time, intense care unit (ICU) stay, and the incidence of hospital-acquired pneumonia.@*RESULTS@#The 28-d mortality in the acupuncture group was lower than that in the control group (22.80% vs. 33.20%, P<0.05). Compared with the control group, the acupuncture group at 7 d showed lower GIF, APACHE II, SOFA, MODS scores, D-lac, DAO, LPS, IAP, and abdominal circumference and higher GCS score, MTL, GAS, and bowel sound frequency (all P<0.05). In addition, the above indices showed simillar changes at 7 d compared with days 1 and 3 (all P<0.05) in the EA group.@*CONCLUSION@#Early EA can improve gastrointestinal function and clinical prognosis in patients with severe TBI complicated by AGI. (Registration No. ChiCTR2000032276).

Effects of astaxanthin on oxidative stress and inflammatory reaction in rats with traumatic brain injury based on Nrf2/HO-1 signaling pathway / 中国药房

OBJECTIVE To investigate the effects of astaxanthin on oxidative stress and inflammatory reaction in rats with traumatic brain injury （TBI）. METHODS Male SD rats were randomly divided into sham operation group， model group， astaxanthin low-dose group （20 mg/kg）， astaxanthin high-dose group （40 mg/kg）， astaxanthin+ML385 group [astaxanthin 40 mg/kg+ nuclear factor-erythroid 2-related factor 2 （Nrf2） inhibitor ML385 30 mg/kg]， with 14 rats in each group. Except for the sham operation group， TBI model was induced by the modified Feeney free-fall impact method in other groups. The rats in each drug group were given the corresponding drug intragastrically or intraperitoneally， and the rats in the sham operation group and model group were intragastrically given a constant volume of normal saline. The neurological function of rats in each group was scored on the 1st， 3rd and 7th day after drug intervention； on the 7th day of drug intervention， the changes of cerebral histomorphology and inflammatory infiltration score were observed in each group， and the ultrastructure of nerve cells in brain tissue was also observed. The contents of oxidative stress indexes [superoxide dismutase （SOD）， catalase （CAT）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， nitric oxide （NO）] and inflammatory reaction indexes [tumor necrosis factor-α， interleukin-1β （IL-1β）， IL-6， inducible nitric oxide synthase] as well as protein and mRNA expressions of Nrf2， heme oxygenase-1 （HO-1） and NAD（P）H： quinone oxidoreductase 1 （NQO1） were detected in cerebral tissue. RESULTS Compared with the sham operation group， the brain edema of rats in the model group was obvious， accompanied by a large number of inflammatory cells infiltrated， the shape of organelles was damaged and their number was reduced， and the ultrastructure of nerve cells was seriously damaged. The neurological function score， the contents of SOD， CAT， GSH-Px and NO and the relative expression levels of Nrf2， HO-1 and NQO1 protein and mRNA in brain tissue were significantly decreased， while the inflammatory infiltration scores， the contents of MDA and inflammatory reaction indexes were significantly increased （P＜0.05）. Compared with the model group， low-dose and high-dose astaxanthin could significantly improve the pathological status of brain tissue and nerve cells and neurological function scores （except for the first day of drug intervention in the astaxanthin low-dose group）， increase the contents of SOD， CAT， GSH-Px and NO and the relative expression levels of Nrf2， HO-1， NQO1 protein and mRNA in brain tissue in a dose-dependent manner， and reduce inflammatory infiltration scores， the contents of MDA and inflammatory reaction indexes （P＜0.05）. ML385 could significantly inhibit the above effects of astaxanthin （P＜0.05）. CONCLUSIONS Astaxanthin may reduce the oxidative stress of TBI model rats， alleviate the neurological damage and reduce the level of inflammation reaction by activating the Nrf2/HO-1 signaling pathway.

Changes in functional connectivity in patients with acute mild traumatic brain injury based on a triple-network model: a resting state functional MRI study / 中华行为医学与脑科学杂志

Objective:To investigate the resting state functional connectivity changes of the " triple network model" composed of salient network (SN), executive control network (ECN) and default mode network (DMN) in patients with acute mild traumatic brain injury (mTBI).Methods:From August 2020 to December 2021, forty-five acute mTBI patients (mTBI group) and 40 healthy controls (HC group) with matched sex, age, and education were included.The Montreal cognitive assessment (MoCA) scale was used to evaluate the cognitive status of all subjects.The resting state network (RNS) was established based on independent component analysis (ICA), and the SN, ECN and DMN were extracted, then functional network connectivity (FNC) was analyzed.Subsequently, the correlation between functional connectivity abnormalities and the performance of cognitive impairment was analyzed.SPSS 19.0 was used for statistical analysis and double sample t test was used for comparison between the tow groups. Results:Compared with HC group, mTBI group had enhanced functional connectivity between SN(L-insula) (MNI: x, y, z=-36, 15, 0, t=3.693)and ECN (left superior parietal gyrus, L-SPG) (MNI: x, y, z=-33, -69, 54, t=3.333)(FDR adjust, P<0.05), and decreased functional connectivity between DMN(left superior frontal gyrus, L-SFG) (MNI: x, y, z=-30, 30, 42, t=-4.063)and DMN(L-angular gyrus)(MNI: x, y, z=-21, -66, 33, t=-4.101)(FDR adjust, P<0.05). For FNC analysis, functional network connectivity in SN(IC26)-DMN(IC8) was enhanced in the acute mTBI group and decreased between SN(IC26)-DMN(IC12) and ECN(IC3)-DMN(IC12). The changes of left superior parietal gyrus functional connection were negatively correlated with MoCA score ( r=-0.627, P<0.01), and SN (IC26) -DMN(IC12) connection was positively correlated with MoCA score ( r=0.411, P=0.005). Conclusions:In patients with acute mTBI, the resting functional connectivity changes within and between the networks of the " triple network model" composed of SN, ECN and DMN, and is related to the decline of cognitive function.This will help to better understand the neuropathological mechanism of acute mTBI and post-traumatic cognitive impairment, and may become an effective imaging marker for identifying and predicting cognitive impairment after mTBI.

Correlation between serum zinc and brain injury in infants with mild gastroenteritis complicated with benign infantile convulsion and febrile convulsion / 中华危重病急救医学

Objective:To investigate the association between serum zinc levels and convulsive brain injury in infants with mild gastroenteritis complicated with benign infantile seizures (BICE) and febrile seizures (FC).Methods:A case-control study method was conducted. 120 children with mild gastroenteritis and convulsion admitted to the First Affiliated Hospital of Hebei North University from January 2020 to January 2022 were enrolled as the research subjects. They were divided into BICE group and FC group according to the type of convulsion. The serum zinc level, the frequency and duration of convulsion, and the occurrence of convulsive brain injury in the two groups were recorded. Multivariate Logistic regression analysis was used to screen the risk factors for convulsive brain injury. The Spearman correlation method was used to analyze the association between serum zinc levels, clinical characteristics of convulsion and convulsive brain injury.Results:A total of 120 children were enrolled, of which 81 developed to BICE and 39 developed to FC during hospitalization. The serum zinc level of children in the FC group was significantly lower than that in the BICE group (μmol/L: 39.24±6.50 vs. 48.65±7.21, P < 0.01). In the BICE group and FC group, the serum zinc level in children with more than 2 convulsions was significantly lower than that in the children with one convulsion (μmol/L: 37.65±6.50 vs. 53.17±7.55 in the BICE group, and 30.27±5.58 vs. 44.16±7.57 in the FC group, both P < 0.01). Serum zinc level in children with convulsion duration ≥5 minutes was significantly lower than that in the children with convulsion duration < 5 minutes (μmol/L: 38.75±6.74 vs. 51.21±7.58 in the BICE group, and 31.08±5.46 vs. 45.19±7.25 in the FC group, both P < 0.01). Moreover, the serum zinc level of children with different convulsion frequency and duration in the FC group was significantly lower than that in the BICE group (all P < 0.01). Among the 120 children, 9 cases of convulsive brain injury occurred, and the incidence rate was 7.50%. The incidence of convulsive brain injury in the BICE group was 1.23% (1/81), which was significantly lower than 20.51% in the FC group (8/39, P < 0.01). The serum zinc level of children with convulsive brain injury was significantly lower than that of children with non-brain injury (μmol/L: 28.50±5.00 vs. 60.22±7.31, P < 0.01), and the number of convulsion was significantly higher than that of non-cerebral injury (≥ 2 convulsions: 100.00% vs. 1.80%, P < 0.01), and the duration of convulsion in children with brain injury was significantly longer than that of non-brain-injured children (convulsion duration ≥5 minutes: 100.00% vs. 11.71%, P < 0.01). Multivariate Logistic regression analysis showed that decreased serum zinc level [odds ratio ( OR) = 2.147, 95% confidence interval (95% CI) was 1.354-3.403], increased number of convulsion ( OR = 3.452, 95% CI was 1.266-9.417), and prolonged convulsion duration ( OR = 3.117, 95% CI was 1.326-7.327) were independent risk factor for convulsive brain injury in children with mild gastroenteritis and convulsion (all P < 0.05). Spearman correlation analysis showed that serum zinc level, convulsion ≥2 times, duration of convulsion ≥5 minutes and convulsion ≥2 times + convulsion duration ≥5 minutes were significantly negatively correlated with the occurrence of convulsive brain injury in FC children ( r values were -0.546, -0.517, -0.522, and -0.528, all P < 0.01). There was no significant correlation between serum zinc level, convulsion ≥2 times, convulsion duration ≥5 minutes and convulsion ≥2 times+convulsion duration ≥5 minutes and convulsive brain injury in BICE children ( r values were -0.281, -0.129, -0.201, -0.243, all P > 0.05). Conclusions:Serum zinc level is related to the characteristics of convulsive symptoms in children with mild gastroenteritis complicated with FC, and has a strong negative correlation with the occurrence of convulsive brain injury. Active targeted intervention and treatment may help reduce the incidence of brain injury in children.

Summary of the best evidence for intracranial hypertension care in adults with severe brain injury / 中国实用护理杂志

Objective:To summarize the best evidence of intracranial hypertension nursing for adult patients with severe brain injury, and to provide reference for clinical nursing practice.Methods:According to the evidence-based methodology, a systematic search of Chinese and English literature on intracranial hypertension nursing of adult patients with severe brain injury was conducted in domestic and foreign databases such as CNKI, Wanfang, PubMed, Cochrane Library and Cinahl Plus and so on, as well as related guide websites and professional association websites from the establishment of database to August 2022. Two researchers independently evaluated literature quality and screened evidence, and then the project team summarized and concluded the evidence.Results:A total of 6 009 articles were obtained through preliminary search, and 33 articles were included after screening, including 13 guidelines, 1 systematic review, 17 expert consensus, 1 evidence summary, and 1 meta-analysis. In total, 33 pieces of best evidence were obtained from 8 dimensions, including intracranial pressure related threshold, assessment and monitoring, respiratory care, circulation care, analgesic and sedative care, temperature care, nutrition care and cerebrospinal fluid care.Conclusions:This study summarizes the evidence-based basis of intracranial hypertension nursing in adult patients with severe brain injury, which provides a basis for the standardized construction of clinical nursing strategies and empirical research.