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.

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.

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.

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.

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.

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.

Role and mechanism of tubastatin A in alleviating brain injury after cardiopulmonary resuscitation by inhibiting endoplasmic reticulum stress-mediated cell apoptosis in swine / 中华急诊医学杂志

Objective:To explore the role and mechanism of tubastatin A (TubA) in alleviating brain injury after cardiac arrest and cardiopulmonary resuscitation (CA-CPR) by inhibiting endoplasmic reticulum stress-mediated cell apoptosis in swine.Methods:Twenty-three conventional male white swine, weighing 33-40 kg, aged 4 to 6 months, were divided into 3 groups by random number table method: sham group ( n=6), CA-CPR group ( n=9), and TubA group ( n=8). The CA-CPR swine model was established by 9 min of electrically induced CA through pacing catheter in the right ventricle and then 6 min of CPR in the CA-CPR group. The CA-CPR swine model was established by the same method, and then a dose of 4.5 mg/kg of TubA at 5 min after resuscitation was intravenously infused in the TubA group. The serum concentrations of neuron specific enolase (NSE) and S100β protein (S100β) were measured using ELISA before modeling and at 1, 2, 4 and 24 h after resuscitation. Neurological deficit score (NDS) was evaluated at 24 h after resuscitation. Thereafter, the animals were euthanized, and brain cortex tissues were harvested, and the expression levels of caspase-12 and caspase-3 were measured using immunohistochemistry. Cell apoptosis index was detected by TUNEL assay. The variables among the three groups were compared with one-way analysis of variance and the Bonferroni hoc test using SPSS software. Results:Twenty-four h after resuscitation, the serum concentrations of NSE and S100β were significantly increased, and NDS was markedly elevated in the CA-CPR and TubA groups compared with the sham group (all P<0.05). Compared with the CA-CPR group, serum concentration of NSE starting 2 h after resuscitation and serum concentration of S100β starting 1 h after resuscitation were significantly decreased in the TubA group [NSE (ng/mL): (23.1±2.0) vs. (20.2±2.0) at 2 h, (28.4±2.3) vs. (23.7±1.9) at 4 h, (32.1±2.7) vs. (26.6±2.0) at 24 h; S100β (pg/mL): (2239±193) vs. (1923±101) at 1 h, (2817±157) vs. (2360±141) at 2 h, (3384±250) vs. (2691±210) at 4 h, (3965±303) vs. (3119±260) at 24 h, all P<0.05], and NDS was markedly reduced (240±30 vs. 63±44, P<0.05). At 24 h after resuscitation, brain cortex tissue detection showed that the expression levels of caspase-12 and caspase-3 were significantly increased, and cell apoptosis index was markedly elevated in the CA-CPR and TubA groups compared with the sham group (all P<0.05). However, the expression levels of caspase-12 and caspase-3 were significantly decreased [caspase-12:(7.1±0.7) vs. (4.2±0.4); caspase-3: (13.3±1.6) vs. (7.7±0.8), all P<0.05], and cell apoptosis index was markedly reduced in the TubA group compared to the CA-CPR group [(31.1±8.6) vs. (17.3±2.2), P<0.05]. Conclusions:TubA alleviates brain injury and neurological dysfunction after CA-CPR in swine, which may be related to the inhibition of cell apoptosis mediated by endoplasmic reticulum stress.

Role of SIRT1 in regulating endoplasmic reticulum stress in early brain injury after subarachnoid hemorrhage / 国际生物医学工程杂志

Objective:To investigate the effect of Sirtuin 1 (SIRT1) on subarachnoid hemorrhage (SAH) and its possible mechanism.Methods:A mouse model of SAH was constructed by internal carotid artery puncture. The protein and mRNA expression levels of SIRT1 at 0, 3, 6, 12, 24, 48, and 72 h were detected by Western Blot and qRT-PCR. A Western Blot assay was used to examine SIRT1 and the expression levels of endoplasmic reticulum stress-related markers GRP78, p-PERK/PERK, p-eIF2α/eIF2α, and CHOP after administration of a SIRT1 inhibitor or SIRT1 si-RNA. At 24 h after SAH, subarachnoid hemorrhage volume, neurological function score, brain water content, and blood-brain barrier integrity were measured.Results:The highest expression of SIRT1 protein and mRNA was observed at 24 h compared with other time points, and the differences were statistically significant (all P < 0.001). Inhibition of SIRT1 expression leads to increased expression of endoplasmic reticulum stress-related proteins GRP78, p-PERK/PERK, p-eIF2α/eIF2α, and CHOP, exacerbating hemorrhage and brain water content, disrupting blood-brain barrier integrity, and significantly reducing neurological function scores. Conclusions:Inhibition of SIRT1 expression significantly increased the endoplasmic reticulum response to excitation and exacerbated early brain injury after SAH.

Progress in endogenous neural stem cells for neonatal brain injury / 国际儿科学杂志

Neonatal brain injury refers to the pathological damage of brain tissue caused by various factors in the perinatal period.The most common disorders are hypoxic-ischemic encephalopathy, periventricular-intraventricular hemorrhage, and periventricular leukomalacia.After a severe brain injury, the repair and reconstruction of the central nervous system (CNS) is crucial in restoring CNS architecture and function.The studies have shown that neural stem cells (NSC) have the potential for multidirectional differentiation and the ability to maintain self-renewal.Endogenous neural stem cells (eNSC) can proliferate, migrate to the lesion sites and finally differentiate into astrocytes, oligodendrocytes, and neurons, to provide new options for the treatment of neural regeneration.This paper aims to review the recent progress of eNSC in treating neonatal brain injury.

The mechanism of necrotizing enterocolitis-associated brain injury in neonates / 国际儿科学杂志

Necrotizing enterocolitis(NEC)is a serious gastrointestinal disease in the neonatal period and one of the main causes of death in premature infants.In recent years, with the advancement of neonatal intensive care, the survival rate of children with NEC has been improved.However, the survivors are often accompanied by poor neurological prognoses, such as periventricular leukomalacia, intraventricular hemorrhage, neurodevelopmental disorders.The pathogenesis of NEC has not been fully elucidated.This review discusses the factors that may influence NEC related brain injury, such as hypoxia and ischemia, inflammatory response, nutrition, and brain-gut axis, in order to provide an overview on the pathogenesis of NEC.