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.

The current situation of knowledge, attitude and practice about target temperature management in patients with severe traumatic brain injury among intensive care unit nurses and its factors analysis / 中国实用护理杂志

Objective:To understand the current situation of knowledge, attitude and practice about target temperature management (TTM) in patients with severe traumatic brain injury (STBI) among intensive care unit ICU nurses and analyze the influencing factors, so as to provide a reference for conducting ICU nurses′ TTM training for patients with STBI.Methods:Applying the method of cross-sectional study, from November to December 2022, a stratified whole-group sampling method was used, stratified by first-, second-, and third-level hospitals, and a self-designed questionnaire on the current status of ICU nurses′TTM for patients with STBI was used to investigate the current status of knowledge, attitude, and practice of neurosurgical ICU, emergency ICU, and comprehensive ICU nurses in 22 second- and third-level hospitals in 11 cities in Gansu Province, and multiple linear regression analysis was used to analyze the factors influencing ICU nurses′ knowledge, attitude, and practice scores.Results:A total of 543 valid questionnaires were returned, and the scores of ICU nurses on the TTM total score, knowledge, attitude and practice dimensions of STBI patients were (76.75 ± 10.42), (7.38 ± 2.74), (39.57 ± 4.87), (29.80 ± 7.18) points respectively. The results of multiple linear regression analysis showed that the factor influencing ICU nurses′ scores on the TTM knowledge dimension for STBI patients was having attended TTM-related training ( t = 2.16, P<0.05); the factors influencing ICU nurses′ scores on the TTM attitude dimension for STBI patients were college, bachelor′s degree and the position of nurse practitioner ( t = 2.65, 2.91, 2.14, all P<0.05); and the factors influencing ICU nurses′ scores on the TTM practice dimension for STBI patients were the age group of 36 to 45 years old, the department having TTM-related criteria and having knowledge of TTM-related guidelines ( t = -2.46, 2.64, 3.85, all P<0.05). Conclusions:ICU nurses have a more positive attitude toward TTM in patients with STBI, but the level of knowledge and practice needs to be improved. Managers should conduct relevant training according to the current situation and influencing factors to improve ICU nurses′ knowledge and practice of TTM in patients with STBI, ensuring the effectiveness and safety of TTM.

Occurrence of hypopituitarism after severe craniocerebral trauma and its predictors / 中华内分泌外科杂志

Objective:To investigate the occurrence and predictors of hypopituitarism after traumatic brain injury (TBI) .Methods:A prospective study was conducted on 185 patients with severe TBI in the Emergency Department of the First Hospital of Shanxi Medical University from Jan. 2020 to May. 2022, of whom 108 were male and 77 were female; age ranged from 18 to 79 years, mean (51.32±9.34) years. Pituitary function was assessed within 3-7 d after the onset of TBI, and the occurrence of hypopituitarism after severe TBI was counted. 41 cases in the hypopituitarism group, 26 males and 15 females, aged (52.76±9.83) years, were divided into the hypopituitarism group (hypopituitarism occurred) and the non-hypopituitarism group (hypopituitarism did not occur) according to whether hypopituitarism occurred. In the non-decompensated group, there were 144 cases, 82 males and 62 females, aged (50.91±9.27) years. The clinical data of the decompensated and non-decompensated groups were compared, and the factors influencing the occurrence of hypopituitarism were analysed, and a logistic prediction model was constructed based on the relevant influencing factors. The value of this model in predicting the occurrence of hypopituitarism after severe TBI was evaluated by using the receiver operating characteristic (ROC) curve.Results:The prevalence of hypopituitarism in the 185 patients with severe TBI in this study was 22.16%; the Glasgow coma scale (GCS) score on admission was lower in the decompensated group than in the non-decompensated group [ (6.36±1.04) vs (7.48±0.59) ], the percentage of hyperbaric oxygen therapy was lower than in the non-decompensated group (21.95% vs 49.31%) , the percentage of intracranial pressure (82.93% vs 49.31%) , midline displacement ≥5 mm (78.05% vs 29.86%) , skull base fracture (34.15% vs. 17.36%) , diffuse cerebral edema (19.51% vs 4.17%) , and serum brain derived neurophic factor (BDNF) . Brain derived neurophic factor (BDNF) was higher than that in the non-reduced group [ (6.35±1.29) ng/ml vs (4.51±1.06) ng/ml], and neuronal-specific enolase (NSE) was higher than that in the non-reduced group [ (33.06±5.42) μg/L vs (23.15±4.97) μg/L]. (4.97) μg/L]. Vascular epithelial growth factor (VEGF) was higher than that in the non-reduced group [ (312.07±24.35) pg/ml vs (226.80±20.96) pg/ml], tumor necrosis factor-α (TNF-α) was higher than that in the non-reduced group [ (281.24±38.91) ng/L vs (186.91) pg/ml], and tumor necrosis factor-α (TNF-α) was higher than that in the non-reduced group (186.55±35.72) ng/L (all P<0.05) . Increased intracranial pressure, midline displacement ≥5 mm, diffuse cerebral edema, serum BDNF, NSE, VEGF, and TNF-α levels were all independent risk factors for the development of hypopituitarism after severe TBI, with admission GCS score and hyperbaric oxygen therapy as protective factors ( P<0.05) ; a logistic prediction model was constructed based on the influencing factors as: Logit ( P) = 5.264-0.880×admission GCS score + 1.618×increased intracranial pressure + 1.941×midline displacement ≥5 mm + 1.289×diffuse cerebral edema+1.306×BDNF+1.426×NSE+1.781×VEGF+1.615×TNF-α-0.758×hyperbaric oxygen therapy; the model predicted the occurrence of severe TBI after the area under the curve (AUC) of hypopituitarism was 0.930 (95% CI 0.883-0.962) , with a predictive sensitivity and specificity of 90.24% and 89.19%, respectively. Conclusions:The incidence of hypopituitarism is higher after severe TBI. Increased intracranial pressure, midline displacement ≥5 mm, diffuse cerebral edema, serum BDNF, NSE, VEGF and TNF-α levels are all used as predictors of hypopituitarism.

Protective effect and mechanism of zonisamide on oxygen-glucose deprivation cell model of traumatic brain injury / 中华急诊医学杂志

Objective:To explore the protective effect of zonisamide (ZNS) on oxygen-glucose deprivation (OGD) cell model of traumatic brain injury (TBI), and its underlying mechanism.Methods:Human neuroblastoma cells (SH-SY5Y) were cultured in vitro and divided into the control group, OGD group, and drug administration group (OGD+ZNS group) according to the random number table method. The OGD method was used to establish a TBI cell model. After modeling, the cell activity, the release of lactate dehydrogenase (LDH), and β-galactosidase staining were detected to evaluate cell function and senescence. Additionally, mitochondrial morphology and potential membrane changes were observed using Mito Tracker Red and JC-1 mitochondrial membrane potential staining. ATP concentration was measured, and protein was extracted from SH-SY5Y cells and then subjected to Western blot analysis to detect endoplasmic reticulum stress-related markers, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), protein disulfide isomerase (PDI), and β-actin.Results:The OGD group had a significantly lower cell survival rate compared to the control group ( P<0.01), while the OGD+ZNS group had a significant higher cell survival rate than the OGD group ( P<0.01). The LDH release rate was significantly higher in the OGD group than in the control group ( P<0.01), while the OGD+ZNS group had a significant lower LDH release rate compared to the OGD group ( P<0.01). Moreover, the cell staining results indicated that compared to the control and OGD+ZNS groups, the cells in the OGD group exhibited significant damage and senescence with darker staining while the mitochondrial staining results demonstrated a significant reduction in mitochondrial linear junctions and decreased mitochondrial activity in the OGD group compared to the control and OGD+ZNS groups. Compared to the control and OGD+ZNS groups, the OGD group exhibited a significant reduction in mitochondrial staining red fluorescence, a significant increase in green fluorescence, and a significant decrease in mitochondrial membrane potential. The OGD group demonstrated a significant decrease in ATP concentration compared to the control group ( P<0.01), whereas the OGD+ZNS group exhibited a significant higher ATP concentration compared to the OGD group ( P<0.01). Western blot analysis revealed significant upregulation of GRP78, CHOP, and PDI in the OGD group compared to the control group (all P<0.05), while in the OGD+ZNS group, the expression levels of these proteins were significantly downregulated compared to the OGD group (all P<0.05). Conclusions:Zonisamide can protect OGD TBI cell model by preserving mitochondrial activity and inhibiting endoplasmic reticulum stress.

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.

Long-term impact of mild traumatic brain injury on oculomotor parameters / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the long-term impact of mild traumatic brain injury(mTBI)on oculomotor parameters.METHODS: Prospective study. A total of 46 patients from 6 to 12mo after mTBI who visited Tianjin Eye Hospital from February to August 2021 were collected. According to the score of the Brain Injury Vision Sympton Survey(BIVSS)Questionnaire, they were divided into the symptomatic group of mTBI(BIVSS total score ≥32, n=24)and the asymptomatic group of mTBI(BIVSS total score &#x0026;#x003C;32, n=22). In addition, healthy people without mTBI were selected as the control group(n=23). All of the subjects accepted test of oculomotor parameters to evaluate binocular vision.RESULTS: Monocular accommodation amplitude, monocular accommodation facility, the absolute value of phoria at near, BI recovery point of fusional range at near and saccades were different among the three groups(P&#x0026;#x003C;0.05); There were no significant differences in near point of convergence, the absolute value of distance phoria, BI blur, BO blur and recovery of fusional range at near among the three groups(P&#x0026;#x003E;0.05). The incidence of accommodative abnormality, convergence abnormality, and saccadic dysfunction were different among the three groups(P&#x0026;#x003C;0.01). The incidence of accommodative abnormality in the symptomatic group was significantly higher than that in the asymptomatic and control groups(all P&#x0026;#x003C;0.0167); the incidence of convergence dysfunction in the symptomatic and the asymptomatic groups were higher than that in the control group(all P&#x0026;#x003C;0.0167); the incidence of saccadic dysfunction in the symptomatic group was significantly higher than that in the asymptomatic and control groups(all P&#x0026;#x003C;0.0167).CONCLUSION: Accommodation, convergence, and saccades functions in the mTBI symptomatic group were lower, and some of the binocular vision in the asymptomatic group was also affected. It is suggested that mTBI has a long-term impact on oculomotor parameters, and comprehensive oculomotor assessment is necessary for mTBI patients.

Effects of Sevoflurane and Propofol on Neurological Recovery of Traumatic Brain Injury Patients in the Early Postoperative Stage: A Retrospective Cohort Study / 中国医学科学杂志(英文版)

Objective To investigate the effects of propofol and sevoflurane on neurological recovery of traumatic brain injury (TBI) patients in the early postoperative stage.Methods We retrospectively analyzed the clinical data of TBI patients who underwent craniotomy or decompressive craniectomy. Generalized additive mixed model (GAMM) was used to analyze effects of propofol and sevoflurane on Glasgow Coma Scale (GCS) on postoperative days 1, 3, and 7. Multivariate regression analysis was used to analyze effects of the two anesthetics on Glasgow Outcome Scale (GOS) at discharge.Results A total of 340 TBI patients were enrolled in this study. There were 110 TBI patients who underwent craniotomy including 75 in the propofol group and 35 in the sevoflurane group, and 134 patients who underwent decompressive craniectomy including 63 in the propofol group and 71 in the sevoflurane group. It showed no significant difference in GCS at admission between the propofol and the sevoflurane groups among craniotomy patients (β = 0.75, 95%CI: -0.55 to 2.05, P = 0.260). However, elevation in GCS from baseline was 1.73 points (95%CI: -2.81 to -0.66, P = 0.002) less in the sevoflurane group than that in the propofol group on postoperative day 1, 2.03 points (95%CI: -3.14 to -0.91, P < 0.001) less on day 3, and 1.31 points (95%CI: -2.43 to -0.19, P = 0.022) less on day 7. The risk of unfavorable GOS (GOS 1, 2, and 3) at discharge was higher in the sevoflurane group (OR = 4.93, 95%CI: 1.05 to 23.03, P = 0.043). No significant difference was observed among two-group decompressive craniectomy patients in GCS and GOS.Conclusions Compared to propofol, sevoflurane was associated with worse neurological recovery during the hospital stay in TBI patients undergoing craniotomy. This difference was not detected in TBI patients undergoing decompressive craniectomy.

Research progress of fibroblast growth factor in nervous system diseases / 浙江大学学报·医学版

Fibroblast growth factors (FGF) are a group of structurally related polypeptides which constitute an elaborate signaling system with their receptors. Evidence accumulated in the years suggests that the FGF family plays a key role in the repair of central nervous system injury. The main protective mechanisms include activating the expression of PI3K-Akt, peroxisome proliferator-activated receptor (PPARγ) and other signals; inhibiting NF-κB-mediated inflammatory response, oxidative stress and apoptosis; regulating neuronal differentiation and neuronal excitability as well as participating in protection of neurovascular units and nerve function repair. This paper comprehensively summarizes the latest research progress in FGF signaling related to diseases of the central nervous system such as cerebral infarction, cerebral hemorrhage, traumatic brain injury, Alzheimer's disease, Parkinson's disease, epilepsy and depression, aiming to provide scientific basis and reference for the development of innovative FGF drugs for the prevention and treatment of neurological diseases.

A pilot study on the effects of early use of valproate sodium on neuroinflammation after traumatic brain injury / 中国当代儿科杂志

OBJECTIVES@#To study the effect of early use of sodium valproate on neuroinflammation after traumatic brain injury (TBI).@*METHODS@#A total of 45 children who visited in Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from August 2021 to August 2022 were enrolled in this prospective study, among whom 15 healthy children served as the healthy control group, and 30 children with TBI were divided into a sodium valproate treatment group and a conventional treatment group using a random number table (n=15 each). The children in the sodium valproate treatment group were given sodium valproate in addition to conventional treatment, and those in the conventional group were given an equal volume of 5% glucose solution in addition to conventional treatment. The serum concentrations of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured in the healthy control group on the day of physical examination and in the children with TBI on days 1, 3, and 5 after admission. Glasgow Outcome Scale-Extended (GOS-E) score was evaluated for the children with TBI 2 months after discharge.@*RESULTS@#Compared with the healthy control group, the children with TBI had significantly higher serum concentrations of NLRP3, HMGB1, TNF-α, and IL-1β on day 1 after admission (P<0.017). The concentration of NLRP3 on day 5 after admission was significantly higher than that on days 1 and 3 after admission in the children with TBI (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of NLRP3 than the conventional treatment group (P<0.05). For the conventional treatment group, there was no significant difference in the concentration of HMGB1 on days 1, 3, and 5 after admission (P>0.017), while for the sodium valproate treatment group, the concentration of HMGB1 on day 5 after admission was significantly lower than that on days 1 and 3 after admission (P<0.017). On day 5 after admission, the sodium valproate treatment group had a significantly lower concentration of HMGB1 than the conventional treatment group (P<0.05). For the children with TBI, the concentration of TNF-α on day 1 after admission was significantly lower than that on days 3 and 5 after admission (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of TNF-α than the conventional treatment group (P<0.05). The concentration of IL-1β on day 3 after admission was significantly lower than that on days 1 and 5 after admission (P<0.017) in the children with TBI. On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of IL-1β than the conventional treatment group (P<0.05). The GOS-E score was significantly higher in the sodium valproate treatment group than that in the conventional treatment group 2 months after discharge (P<0.05).@*CONCLUSIONS@#Early use of sodium valproate can reduce the release of neuroinflammatory factors and improve the prognosis of children with TBI.

Xingnao Kaiqiao acupuncture on promoting wake-up of consciousness disorder in children with early severe traumatic brain injury / 中国针灸

OBJECTIVE@#To observe the awakening effect and safety of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on consciousness disorder in children with early severe traumatic brain injury (STBI) based on western medicine treatment.@*METHODS@#A total of 62 children with STBI were randomly divided into an observation group (31 cases,1 case dropped off) and a control group (31 cases, 1 case dropped off). The control group was treated with routine rehabilitation therapy (6 times a week for 30 days), and intravenous drip of cattle encephalon glycoside and ignotin injection (once a day for 28 days). On the basis of the treatment in the control group, the observation group was treated with Xingnao Kaiqiao acupuncture at Neiguan (PC 6), Shuigou (GV 26), Yintang (GV 24+), Baihui (GV 20), Sanyinjiao (SP 6), Zusanli (ST 36), etc., and supplementary acupoints according to clinical symptoms, once a day, 6 times a week for 30 days. The scores of Glasgow coma scale (GCS), coma recovery scale-revised (CRS-R) and modified Barthel index (MBI) were observed before treatment and 10, 20 and 30 d into treatment. Electroencephalogram (EEG) grading before and after treatment was observed in the two groups, and safety was evaluated.@*RESULTS@#After 10, 20 and 30 days of treatment, the scores of GCS, CRS-R and MBI in the two groups were increased compared before treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). After treatment, EEG grading of both groups was improved compared with that before treatment (P<0.05), and the observation group was better than the control group (P<0.05). There were no adverse events or adverse reactions in the two groups during treatment.@*CONCLUSION@#On the basis of western medicine treatment, Xingnao Kaiqiao acupuncture plays a remarkable role in wakening the early STBI children, can improve the level of consciousness disorder and daily living ability, and it is safe and effective.

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.

The mechanism of the receptors for advanced glycation end products affecting pericyte detachment from blood vessels after traumatic brain injury / 西安交通大学学报(医学版)

【Objective】 To observe the reactive change of cortical perivascular cells after craniocerebral injury and explore its mechanism. 【Methods】 The controllable cortical impact animal model was used to simulate craniocerebral injury, the expressions of cortical pericyte markers at different time points after trauma were studied by Western blotting, and the biological behavior of vascular pericytes after craniocerebral injury was determined by transmission electron microscopy. Post-traumatic high mobility group box 1 (HMGB1), receptor for advanced glycation end product (RAGE), and nuclear factor κB (NF-κB) were detected by Western blotting. The experimental animals were divided into FPS-ZM1 (a specific RAGE receptor blocker) injection group and wild-type group. Wet and dry brain weight and transmission electron microscopy were used to study the post-traumatic effects of HMGB1-RAGE on pericytes. The primary mouse brain microvascular pericytes were cultured and supplemented with HMGB1 recombinant protein; the cultured pericytes supplemented with FPS-ZM1 were used as the control to explore the effect of HMGB1-RAGE pathway on vascular pericytes in vitro. 【Results】 The expression levels of early post-traumatic cortical pericyte markers platelet-derived growth factor receptor beta (PDGFR-β) and NG2 proteoglycan (NG2) decreased (PDGFR-β, Control vs. CCI 3D P<0.05; NG2, Control vs. CCI 6H P<0.05; Control vs. CCI 1D P<0.05). We found that pericytes were detached from blood vessels, accompanied by local blood-brain barrier opening. The expression of HMGB1-RAGE-NF-κB signaling pathway was increased in the early cortex after trauma (HMGB1, Control vs. CCI 6H P<0.05, Control vs. CCI 1D P<0.05; RAGE, Control vs. CCI 6H P<0.05, Control vs. CCI 1D P<0.05, Control vs. CCI 3D P<0.05, Control vs. CCI 5D P<0.05, Control vs. CCI 7D P<0.05; NF-κB, Control vs. CCI 6H P<0.05, Control vs. CCI 1D P<0.05). After blocking the binding of RAGE with the ligand, cortical edema was reduced (CCI 6H P<0.05, CCI 1D P<0.05), and neurovascular unit damage was reduced. HMGB1 recombinant protein could increase the migration ability of cultured pericytes (Control vs. HMGB1 P<0.05, Control vs. HMGB1+FPS-ZM1 P<0.05), and could be reversed by FPS-ZM1 (HMGB1 vs. HMGB1+FPS-ZM1 P<0.05). 【Conclusion】 High-level HMGB1 after traumatic brain injury mediates pericytes’ detachment from blood vessels through RAGE on pericytes and leads to the occurrence of local cerebral edema.

Construction of blood transfusion prediction model for patients with severe traumatic brain injury / 中国输血杂志

【Objective】 To construct a blood transfusion prediction model for patients with severe traumatic brain injury (TBI), in order to predict the risk of blood transfusion and guide blood transfusion decision-making. 【Methods】 The clinical data of 756 patients with severe TBI admitted to the hospital from January 1, 2015 to June 30, 2021 were retrospectively analyzed. According to whether the patients were transfused with red blood cells after admission, the patients were divided into blood transfusion group (n=354) and non-blood transfusion group (n=402). The basic clinical data and prognostic indicators of the two groups were compared. Logistic regression algorithm was used to screen the risk factors related to blood transfusion in hospital to establish a nomogram prediction model, and the performance of the model was evaluated. 【Results】 No significant differences were noticed in gender, age, body temperature, cause of injury, ABO blood group, Rh blood group, serum Na and K concentrations between the two groups (P>0.05). Significant differences were found in Glasgow coma score (GCS), heart rate (HR), systolic blood pressure (SP), diastolic blood pressure (DP), shock index (SI), respiratory rate (RR), clinical diagnosis, treatment, hemoglobin concentration (Hb), hematocrit (Hct), platelet count (Plt) and coagulation function between the two groups (P0.05). Multivariate logistic regression analysis showed that surgical treatment, skull fracture, hemorrhagic shock, decreased Plt, decreased Hct and increased INR were independent risk factors for blood transfusion. A nomogram prediction model was constructed and the area under the ROC curve of the training set and the test set was 0.819(95% CI: 0.784-0.854) and 0.866(95% CI: 0.818-0.910), respectively, which had good predictive performance. 【Conclusion】 Surgical treatment, skull fracture, hemorrhagic shock, decreased Plt, decreased Hct and increased INR are independent risk factors for blood transfusion in adult patients with severe traumatic brain injury. The nomogram prediction model can better predict the blood transfusion demand of TBI patients and has high application value.

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.

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.