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Comparative transcriptomic analysis of rat versus mouse cerebral cortex after traumatic brain injury

Neural Regeneration Research 2021年第7期16卷 1235-1243页

作者： Meng-Shi Yang Xiao-Jian Xu Bin Zhang Fei Niu bai-yun liu Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Beijing Key Laboratory of Central Nervous System Injury and Department of Neurosurgery Beijing Neurosurgical Institute and Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Nerve Injury and Repair Center of Beijing Institute for Brain Disorders BeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina

The heterogeneity of traumatic brain injury(TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI *** common processes across species may be an innovative strategy to combat debilitating *** the present study, a cross-species transcriptome comparison was performed for the first time to determine the fundamental processes of secondary brain injury in Sprague-Dawley rat and C57/BL6 mouse models of TBI, caused by acute controlled cortical *** RNA sequencing data from the mouse model of TBI were downloaded from the Gene Expression Omnibus(ID: GSE79441) at the National Center for Biotechnology *** the rat data, peri-injury cerebral cortex samples were collected for transcriptomic analysis 24 hours after *** expressed gene-based functional analysis revealed that common features between the two species were mainly involved in the regulation and activation of the innate immune response, including complement cascades as well as Toll-like and nucleotide oligomerization domain-like receptor *** findings were further corroborated by gene set enrichment ***, transcription factor analysis revealed that the families of signal transducers and activators of transcription(STAT), basic leucine zipper(BZIP), Rel homology domain(RHD), and interferon regulatory factor(IRF) transcription factors play vital regulatory roles in the pathophysiological processes of TBI, and are also largely associated with *** findings suggest that targeting the common innate immune response might be a promising therapeutic approach for *** animal experimental procedures were approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No.201802001) on June 6, 2018.

关键词： cognitive impairment cross-species comparison gene set enrichment analysis inflammation innate immune neurodegenerative disease secondary injury transcription factor transcriptome traumatic brain injury

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Protein profiling identified mitochondrial dysfunction and synaptic abnormalities after dexamethasone intervention in rats with traumatic brain injury

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Neural Regeneration Research 2021年第12期16卷 2438-2445页

作者： Fei Niu Bin Zhang Jie Feng Xiang Mao Xiao-Jian Xu Jin-Qian Dong bai-yun liu Department of Neurotrauma Beijing Key Laboratory of Central Nervous System InjuryBeijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Key Laboratory of Central Nervous System Injury Research Center for Brain TumorBeijing Institute of Brain DisordersBeijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Department of Neurosurgery the First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina Center for Nerve Injury and Repair Beijing Institute of Brain DisordersBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina

Dexamethasone has been widely used after various neurosurgical procedures due to its anti-inflammatory property and the abilities to restore vascular permeability,inhibit free radicals,and reduce cerebrospinal fluid *** to the latest guidelines for the treatment of traumatic brain injury in the United States,high-dose glucocorticoids cause neurological *** investigate the reason why high-dose glucocorticoids after traumatic brain injury exhibit harmful effect,rat controlled cortical impact models of traumatic brain injury were *** 1 hour and 2 days after surgery,rat models were intraperitoneally administered dexamethasone 10 mg/*** results revealed that 31 proteins were significantly upregulated and 12 proteins were significantly downregulated in rat models of traumatic brain injury after dexamethasone *** Ingenuity Pathway Analysis results showed that differentially expressed proteins were enriched in the mitochondrial dysfunction pathway and synaptogenesis signaling *** blot analysis and immunohistochemistry results showed that Ndufv2,Maob and Gria3 expression and positive cell count in the dexamethasone-treated group were significantly greater than those in the model *** findings suggest that dexamethasone may promote a compensatory increase in complex I subunits(Ndufs2 and Ndufv2),increase the expression of mitochondrial enzyme Maob,and upregulate synaptic-transmission-related protein *** changes may be caused by nerve injury after traumatic brain injury treatment by *** study was approved by Institutional Ethics Committee of Beijing Neurosurgical Institute(approval No.201802001)on June 6,2018.

关键词： dexamethasone Gria3 Maob mass spectrometry mitochondrial dysfunction Ndufs2 Ndufv2 proteomics synaptic abnormalities traumatic brain injury

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Genome-wide interrogation of transfer RNA-derived small RNAs in a mouse model of traumatic brain injury

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Neural Regeneration Research 2022年第2期17卷 386-394页

作者： Xiao-Jian Xu Meng-Shi Yang Bin Zhang Qian-Qian Ge Fei Niu Jin-Qian Dong Yuan Zhuang bai-yun liu Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Beijing Key Laboratory of Central Nervous System Injury and Department of Neurosurgery Beijing Neurosurgical Institute and Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Nerve Injury and Repair Center of Beijing Institute for Brain Disorders BeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina

Transfer RNA(t RNA)-derived small RNAs(ts RNAs) are a recently established family of regulatory small non-coding RNAs that modulate diverse biological processes. Growing evidence indicates that ts RNAs are involved in neurological disorders and play a role in the pathogenesis of neurodegenerative disease. However, whether ts RNAs are involved in traumatic brain injury-induced secondary injury remains poorly understood. In this study, a mouse controlled cortical impact model of traumatic brain injury was established, and integrated ts RNA and messenger RNA(m RNA) transcriptome sequencing were used. The results revealed that 103 ts RNAs were differentially expressed in the mouse model of traumatic brain injury at 72 hours, of which 56 ts RNAs were upregulated and 47 ts RNAs were downregulated. Based on micro RNA-like seed matching and Pearson correlation analysis, 57 differentially expressed ts RNA-m RNA interaction pairs were identified, including 29 ts RNAs and 26 m RNAs. Moreover, Gene Ontology annotation of target genes revealed that the significantly enriched terms were primarily associated with inflammation and synaptic function. Collectively, our findings suggest that ts RNAs may be associated with traumatic brain injury-induced secondary brain injury, and are thus a potential therapeutic target for traumatic brain injury. The study was approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No. 20190411) on April 11, 2019.

关键词： gene set enrichment analysis inflammation integrated analysis neurodegenerative disease next-generation sequencing secondary injury synaptic function transfer RNA-derived small RNAs transfer RNAs traumatic brain injury

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Neutrophil-derived interleukin-17A participates in neuroinflammation induced by traumatic brain injury

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Neural Regeneration Research 2023年第5期18卷 1046-1051页

作者： Xiao-Jian Xu Qian-Qian Ge Meng-Shi Yang Yuan Zhuang Bin Zhang Jin-Qian Dong Fei Niu Hao Li bai-yun liu Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Beijing Key Laboratory of Central Nervous System Injury and Department of Neurosurgery Beijing Neurosurgical Institute and Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Nerve Injury and Repair Center of Beijing Institute for Brain Disorders BeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina

After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.

关键词： immune infiltration innate immunity interleukin-17A neurodegenerative disease neuroinflammation neutrophils secondary brain injury transcription factor transcriptome traumatic brain injury

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Effects of Sevoflurane and Propofol on Neurological Recovery of Traumatic Brain Injury Patients in the Early Postoperative Stage: A Retrospective Cohort Study

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Chinese Medical Sciences Journal 2023年第2期38卷 97-108页

作者： Bei Wu Wan-Qing Song Jin-Qian Dong Hong-Li Yue Yu Lu yun Yu Shu-Yu Hao bai-yun liu Wei-Hua Cui Department of Anesthesiology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China

Objective To investigate the effects of propofol and sevoflurane on neurological recovery of traumatic brain injury(TBI)patients in the early postoperative *** We retrospectively analyzed the clinical data of TBI patients who underwent craniotomy or decompressive *** additive mixed model(GAMM)was used to analyze effects of propofol and sevoflurane on Glasgow Coma Scale(GCS)on postoperative days 1,3,and *** regression analysis was used to analyze effects of the two anesthetics on Glasgow Outcome Scale(GOS)at *** A total of 340 TBI patients were enrolled in this *** 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 *** 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 *** 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 *** Compared to propofol,sevoflurane was associated with worse neurological recovery during the hospital stay in TBI patients undergoing *** difference was not detected in TBI patients undergoing decompressive craniectomy.

关键词： Glasgow Coma Scale Glasgow Outcome Scale propofol sevoflurane traumatic brain injury

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Tandem Mass Tag-based proteomics analysis reveals the vital role of inflammation in traumatic brain injury in a mouse model

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Neural Regeneration Research 2023年第1期18卷 155-161页

作者： Jin-Qian Dong Qian-Qian Ge Sheng-Hua Lu Meng-Shi Yang Yuan Zhuang Bin Zhang Fei Niu Xiao-Jian Xu bai-yun liu Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Center for Nerve Injury and Repair Beijing Institute of Brain DisordersBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina

Proteomics is a powerful tool that can be used to elucidate the underlying mechanisms of diseases and identify new ***,it may also be helpful for understanding the detailed pathological mechanism of traumatic brain injury(TBI).In this study,we performed Tandem Mass Tag-based quantitative analysis of cortical proteome profiles in a mouse model of *** results showed that there were 302 differentially expressed proteins in TBI mice compared with normal mice 7 days after *** Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that these differentially expressed proteins were predominantly involved in inflammatory responses,including complement and coagulation cascades,as well as chemokine signaling *** transcription factor analysis revealed that the inflammation-related transcription factors NF-κB1,RelA,IRF1,STAT1,and Spi1 play pivotal roles in the secondary injury that occurs after TBI,which further corroborates the functional enrichment for inflammatory *** results suggest that inflammation-related proteins and inflammatory responses are promising targets for the treatment of TBI.

关键词： bioinformatics complement cascade mass spectrometry neuroinflammation proteomics secondary injury subacute phase tandem mass tag transcription factor traumatic brain injury

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The effect of green channel for stroke patients on treatment of severe aneurysmal subarachnoid hemorrhage

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Chinese Journal of Traumatology 2024年第6期27卷 328-333页

作者： Xue-Jiao Wang Yu Deng Xiao-Qing Li Feng-Feng Jiang Wen-Yan Jia He-Chun Zhang Feng-Ying Chen bai-yun liu Department of Neurosurgery The Third People's Hospital of DatongDatong037008Shanxi provinceChina Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing100050China Central Laboratory of Datong The Third People's Hospital of DatongDatong037008Shanxi provinceChina Stroke Prevention Office The Third People's Hospital of DatongDatong037008Shanxi provinceChina Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijing100069China Center for Nerve Injury and Repair Beijing Institute of Brain DisordersBeijing100069China China National Clinical Research Center for Neurological Diseases Beijing100069China

Purpose:To explore the effect of green channel for stroke patients on the treatment of severe aneurysmal subarachnoid ***:This is a retrospective case-control *** clinical data of patients with severe aneurysmal subarachnoid hemorrhage admitted to the emergency department of our hospital from January 2015 to June 2022 were retrospectively *** diagnosed with subarachnoid hemorrhage,confirmed intracranial aneurysm by preoperative CT angiography or digital subtraction,graded Hunt-Hess grade III,IV,and V,<72 h from the onset to the time of consultation received surgical treatment in our hospital were included in this *** with serious underlying diseases,such as heart,liver,kidney diseases,or malignant tumors,traumatic subarachnoid hemorrhage,previous history of cerebral hemorrhage,and incomplete data were *** control group included patients with severe aneurysmal subarachnoid hemorrhage admitted from January 2015 to December 2018 before the establishment of the green channel for stroke patients,and the observation group included patients with severe aneurysmal subarachnoid hemorrhage admitted from January 2019 to June 2022 after the establishment of the green *** control group received routine treatment in the emergency department;the observation group received improved treatment of green channel for stroke ***,age,Hunt-Hess grade on admission,modified Rankin scale(mRS)on admission,aneurysm location,aneurysm size and whether accompanied by intracerebral hemorrhage,the time from onset to emergency department,the time from emergency department to vascular diagnostic examination,the time from onset to surgery,the time from emergency department to surgery,the time from hospital admission to surgery,length of hospital stay,complications,treatment effect were analyzed and compared between the 2 *** 23.0 software was utilized to conduct comparisons between the 2 ***-test,Chi-square test,

关键词： Stroke Green channel Aneurysmal subarachnoid hemorrhage

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Protective Effects of Calpain Inhibition on Neurovascular Unit Injury through Downregulating Nuclear Factor-KB- related Inflammation during Traumatic Brain Injury in Mice

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Chinese Medical Journal 2017年第2期130卷 187-198页

作者： Xiao-Gang Tao Jing-Hua Shi Shu-Yu Hao Xue-Tao Chen bai-yun liu Department of Neurosurgery Beijing Tian Tan Hospital Capital Medical University Beijing 100050 China Department of Otolaryngology Beijing Tian Tan Hospital Capital Medical University Beijing 100050 China Department of Neurotrauma Beijing Neurosurgical Institute Capital Medical University Beijing 100050 China

Background： In addition to neurons, all components of the neurovascular unit （NVU）, such as glial, endothelial, and basal membranes, are destroyed during traumatic brain injury （TBI）. Previous studies have shown that excessive stimulation ofcalpain is crucial for cerebral injury after traumatic insult. The objective of this study was to investigate whether calpain activation participated in NVU disruption and edema formation in a mouse model of controlled cortical impact （CCI）. Methods： One hundred and eight mice were divided into three groups： the sham group, the control group, and the MDL28170 group. MDL28170 （20 mg/kg）, an efficient calpain inhibitor, was administered intraperitoneally at 5 rain, 3 h, and 6 h after experimental CCI. We then measured neurobehavioral deficits, calpain activity, inflammatory mediator levels, blood-brain barrier （BBB） disruption, and NVU deficits using electron microscopy and histopathological analysis at 6 h and 24 h after CCI. Results： The MDL28170 treatment significantly reduced the extent of both cerebral contusion （MDL28170 vs. vehicle group, 16.90 ± 1.01 mm3 and 17.20±1.17 mm3 vs. 9.30 ± 1.05 mm^3 and 9.90 ± 1.17 mm3, both P 〈 0.001 ） and edema （M DL28170 vs. vehicle group, 80.76 ± 1.25% and 82.00 ± 1.84% vs. 82.55 ± 1.32% and 83.64 ± 1.25%, both P 〈 0.05）, improved neurological scores （MDL28170 vs. vehicle group, 7.50 ±0.45 and 6.33 ±0.38 vs. 12.33 ± 0.48 and 11.67±0.48, both P 〈 0.001）, and attenuated NVU damage resulting （including tight junction （TJ）, basement membrane, BBB, and neuron） from CCI at 6 h and 24 h. Moreover, MDL28170 markedly downregulated nuclear factor-κB-related inflammation （tumor necrosis factor-α [TNF-α]： MDL28170 vs. vehicle group, 1.15 ± 0.07 and 1.62± 0.08 vs. 1.59±0.10 and 2.18± 0.10, both P 〈 0.001 ： inducible nitric oxide synthase： M DL28170 vs. vehicle group, 4.51± 0.23 vs. 6.23± 0.12, P 〈 0.001 at 24 h; intracellular adhesion molecule- I ： MDL28170 vs. vehicle group, 1.45± 0.13 vs. 1.70 ± 0.12, P

关键词： Calpain Inflammation: Neurovascular Unit: Nuclear Factor-κB Traumatic Brain Injury

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Two Cases of Spinal Tanycytic Ependymoma Associated with Neurofibromatosis Type 2

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Chinese Medical Journal 2017年第7期130卷 872-873页

作者： Xiao-Gang Tao Zong-Gang Hou Shu-Yu Hao Jun-Ting Zhang bai-yun liu Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing 100050 China

INTRODUCTION Tanycytic ependymoma is a rare subtype of the World Health Organization Grade il ependymoma most commonly found in the cervical and thoracic segments of the spinal cord. Spinal tumors in neurofibromatosis type 2 （NF-2） can be intramedullary, extramedullary, or associated with the nerve roots, and there may be multiple tumors at multiple locations in the spine.

关键词： Neurofibromatosis Type 2 Spinal Tumor Tanycytic Ependymoma

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Glucose metabolism:A link between traumatic brain injury and Alzheimer’s disease

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Chinese Journal of Traumatology 2021年第1期24卷 5-10页

作者： Xiao-Jian Xu Meng-Shi Yang Bin Zhang Fei Niu Jin-Qian Dong bai-yun liu Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijing100070China Beijing Key Laboratory of Central Nervous System Injury and Department of Neurosurgery Beijing Neurosurgical Institute and Beijing Tiantan HospitalCapital Medical UniversityBeijing100070China Nerve Injury and Repair Center of Beijing Institute for Brain Disorders Beijing100070China China National Clinical Research Center for Neurological Diseases Beijing100070China

Traumatic brain injury(TBI),a growing public health problem,is a leading cause of death and disability worldwide,although its prevention measures and clinical cares are substantially *** evidence shows that TBI may increase the risk of mood disorders and neurodegenerative diseases,including Alzheimer’s disease(AD).However,the complex relationship between TBI and AD remains *** dysfunction has been the common pathology in both TBI and *** the one hand,TBI perturbs the glucose metabolism of the brain,and causes energy crisis and subsequent *** the other hand,glucose deprivation promotes amyloidogenesis viaβ-site APP cleaving enzyme-1 dependent mechanism,and triggers tau pathology and synaptic *** findings suggest that TBI might facilitate Alzheimer’s pathogenesis by altering metabolism,which provides clues to metabolic link between TBI and *** this review,we will explore how TBI-induced metabolic changes contribute to the development of AD.

关键词： Alzheimer’s disease Traumatic brain injury Glucose metabolism Neurological disorder

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