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Stability of rat models of fluid percussion-induced traumatic brain injury: comparison of three different impact forces

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Neural regeneration Research 2015年第7期10卷 1088-1094页

作者： Yun-peng Lin Rong-cai Jiang Jian-ning Zhang Department of Neurosurgery Tianjin Medical University General Hospital Tianjin Neurological Institute key laboratory of post-trauma neurorepair and regeneration in central nervous system Ministry of Education Tianjin key laboratory of Injuries Variations and Regeneration of Nervous System Tianjin Medical University General Hospital

Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of liquid spikes. Management of impact pressure is a crucial factor that determines the stability of these models, and direction of impact control is another basic element. To improve experimental stability, we calculated a pressure curve by generating repeated impacts using a fluid percussion device at different pendulum angles. A stereotactic frame was used to control the direction of impact. We produced stable and reproducible models, including mild, moderate, and severe traumatic brain injury, using the MODEL01-B device at pendulum angles of 6°, 11° and 13°, with corresponding impact force values of 1.0 ± 0.11 atm（101.32 ± 11.16 k Pa）, 2.6 ± 0.16 atm（263.44 ± 16.21 k Pa）, and 3.6 ± 0.16 atm（364.77 ± 16.21 k Pa）, respectively. Behavioral tests, hematoxylin-eosin staining, and magnetic resonance imaging revealed that models for different degrees of injury were consistent with the clinical properties of mild, moderate, and severe craniocerebral injuries. Using this method, we established fluid percussion models for different degrees of injury and stabilized pathological features based on precise power and direction control.

关键词： nerve regeneration traumatic brain injury fluid percussion impact force pressure curve head fixed impact peak animal models neural regeneration

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Cognitive impairment after traumatic brain injury is associated with reduced long-term depression of excitatory postsynaptic potential in the rat hippocampal dentate gyrus

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Neural regeneration Research 2018年第10期13卷 1753-1758页

作者： Bao-Liang Zhang Yue-Shan Fan Ji-Wei Wang Zi-Wei Zhou Yin-Gang Wu Meng-Chen Yang Dong-Dong Sun Jian-Ning Zhang Department of Neurosurgery Tianjin Medical University General HospitalTianjin Neurological InstituteKey Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous SystemMinistry of EducationTianjin Key Laboratory of InjuriesVariations and Regeneration of Nervous SystemTianjin China

traumatic brain injury can cause loss of neuronal tissue, remote symptomatic epilepsy, and cognitive deficits. However, the mechanisms underlying the effects of traumatic brain injury are not yet clear. Hippocampal excitability is strongly correlated with cognitive dysfunction and remote symptomatic epilepsy. In this study, we examined the relationship between traumatic brain injury-induced neuronal loss and subsequent hippocampal regional excitability. We used hydraulic percussion to generate a rat model of traumatic brain injury. At 7 days after injury, the mean modified neurological severity score was 9.5, suggesting that the neurological function of the rats was remarkably impaired. Electrophysiology and immunocytochemical staining revealed increases in the slope of excitatory postsynaptic potentials and long-term depression（indicating weakened long-term inhibition）, and the numbers of cholecystokinin and parvalbumin immunoreactive cells were clearly reduced in the rat hippocampal dentate gyrus. These results indicate that interneuronal loss and changes in excitability occurred in the hippocampal dentate gyrus. Thus, traumatic brain injury-induced loss of interneurons appears to be associated with reduced long-term depression in the hippocampal dentate gyrus.

关键词： nerve regeneration long-term depression traumatic brain injury hippocampus interneurons excitability dentate gyrus parvalbumin cholecystokinin electrophysiology quantification neural regeneration

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Neutrophil extracellular traps mediate neuro-immunothrombosis

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Neural regeneration Research 2024年第8期19卷 1734-1740页

作者： Jianbo Lou Jianning Zhang Quanjun Deng Xin Chen Department of Neurosurgery Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institute Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous SystemMinistry of EducationTianjin Key Laboratory of InjuriesVariations and Regeneration of Nervous SystemTianjinChina

Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammato ry *** extracellular trap formation occurs through lytic and non-lytic pathways that can be further classified by formation ***,von Willebrand factor,fibrin,and many other factors participate in the interplay between inflammation and *** summarizes the intricate interplay between inflammation and thrombosis during neural development and the pathogenesis of neurological diseases,providing cutting-edge insights into post-neurotrauma thrombotic *** blood-brain barrier defends the brain and spinal cord against external assaults,and neutrophil extracellular trap involvement in blood-brain barrier disruption and immunothrombosis contributes substantially to secondary injuries in neurological *** research is needed to understand how neutrophil extracellular traps promote blood-brain barrier disruption and immunothrombosis,but recent studies have demonstrated that neutrophil extracellular traps play a crucial role in immunothrombosis,and identified modulators of ***,these neurological diseases occur in blood vessels,and the mechanisms are unclear by which neutrophil extracellular traps penetrate the blood-brain barrier to participate in immunothrombosis in traumatic brain *** review discusses the role of neutrophil extracellular traps in neuro-immunothrombosis and explores potential therapeutic interventions to modulate neutrophil extracellular traps that may reduce immunothrombosis and improve traumatic brain injury outcomes.

关键词： inflammation neuro-immunothrombosis neurologic diseases neurotrauma neutrophil extracellular traps platelet thrombosis traumatic brain injury

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Decreased numbers of circulating endothelial progenitor cells are associated with hyperglycemia in patients with traumatic brain injury

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Neural regeneration Research 2019年第6期14卷 984-990页

作者： Hui-Jie Wei Li Liu Fang-Lian Chen Dong Wang Liang Wang Zeng-Guang Wang Rong-Cai Jiang Jing-Fei Dong Jie-Li Chen Jian-Ning Zhang Department of Neurosurgery Tianjin Medical University General HospitalTianjin Neurological InstituteKey Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous SystemMinistry of EducationTianjin Key Laboratory of InjuriesVariations and Regeneration of Nervous System Department of Neurosurgery Peking University International Hospital Thrombosis Research Section Department of MedicineBaylor College of Medicine Department of Neurology Henry Ford Health System

Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their ***, the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear. In this study, 101 traumatic brain injury patients admitted to the Department of Neurosurgery, Tianjin Medical University General Hospital or the Department of Neurosurgery, Tianjin Huanhu Hospital, China, were enrolled from April 2005 to March 2007. The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1, 4, 7, 14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis, respectively. The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined. Compared with controls, the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury, and then increased at 4 days after injury,and reached a peak at 7 days after injury. Compared with controls, blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable. At 1, 4, and 7 days after injury, the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels(r =-0.147, P traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells. This study was approved by the Ethical Committee of Tianjin Medical University General Hospital, China(approval No. 200501) in January 2015.

关键词： nerve regeneration endothelial progenitor cells vascular repair vascular remodeling angiogenesis neovascularization blood glucose hyperglycemia traumatic brain injury mobilization suppression senescence alternative therapy brain damage neural regeneration

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Dynamic changes in growth factor levels over a 7-day period predict the functional outcomes of traumatic brain injury

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Neural regeneration Research 2018年第12期13卷 2134-2140页

作者： Shuai Zhou Dong-Pei Yin Yi Wang Ye Tian Zeng-Guang Wang Jian-Ning Zhang Department of Intensive Care Unit Tianjin Medical University General Hospital Tianjin China Tianjin Neurological Institute Tianjin China key laboratory of post-trauma Neuro-Repair and regeneration in central nervous system Ministry of Education Tianjin China Tianjin key laboratory of Injuries Variations and Regeneration of Nervous System Tianjin China Department of Neurosurgery Tianjin Medical University General Hospital Tianjin China

traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulocyte-colony stimulating factor（G-CSF）, play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended（GOSE）. Patients having a GOSE score of 〉 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI（within 7 days）. This study was registered with the Chinese Clinical Trial Registry（registration number： ChiCTR1800018251） on September 7, 2018.

关键词： nerve regeneration traumatic brain injury vascular endothelial growth factor angiopoietin-1 granulocyte-colony stimulating factor outcomes secondary brain injuries blood-brain barrier brain edema acute phase clinical trial neural regeneration

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Risk factors for corticosteroid insufficiency during the sub-acute phase of acute traumatic brain injury

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Neural regeneration Research 2020年第7期15卷 1259-1265页

作者： Xin Chen Yan Chai Shao-Bo Wang Jia-Chong Wang Shu-Yuan Yue Rong-Cai Jiang Jian-Ning Zhang Department of Neurosurgery General Hospital of Tianjin Medical UniversityTianjinChina Tianjin Neurological Institute Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous SystemMinistry of EducationTianjin Key Laboratory of InjuriesVariations and Regeneration of Nervous SystemTianjinChina Department of Neurosurgery Ordos Central HospitalOrdosInnerMongolia Autonomous RegionChina Department of Neurosurgery Affiliated Haikou Hospital of Xiangya Medical CollegeCentral South UniversityChangshaHunan ProvinceChina

Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid *** illness-related corticosteroid insufficiency can easily occur after traumatic brain injury,but few studies have examined this occurrence.A multicenter,prospective,cohort study was performed to evaluate the function of the hypothalamic-pituitary-adrenal axis and the incidence of critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain *** hundred and forty patients with acute traumatic brain injury were enrolled from the neurosurgical departments of three tertiary-level hospitals in China,and the critical illness-related corticosteroid insufficiency incidence,critical-illness-related corticosteroid insufficiency-related risk factors,complications,and 28-day mortality among these patients was *** illness-related corticosteroid insufficiency was diagnosed in patients with plasma total cortisol levels less than 10μg/dL(275.9 nM)on post-injury day 4 or when serum cortisol was insufficiently suppressed(less than 50%)during a dexamethasone suppression test on post-injury day *** results demonstrated that critical illness-related corticosteroid insufficiency occurred during the sub-acute phase of traumatic brain injury in 5.6%of patients with mild injury,22.5%of patients with moderate injury,and 52.2%of patients with severe *** brain injury-induced critical illness-related corticosteroid insufficiency was strongly correlated to injury severity during the sub-acute stage of traumatic brain *** brain injury patients with critical illness-related corticosteroid insufficiency frequently presented with hemorrhagic cerebral contusions,diffuse axonal injury,brain herniation,and *** in the incidence of hospital-acquired pneumonia,gastrointestinal bleeding,and 28-day mortality were observed between patients with and without critical i

关键词： brain herniation corticosteroid critical illness-related corticosteroid dexamethasone suppression test diffuse axonal injury gastrointestinal bleeding hemorrhagic cerebral contusions hospital-acquired pneumonia insufficiency prognosis traumatic brain injury

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Cold water swimming pretreatment reduces cognitive deficits in a rat model of traumatic brain injury

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Neural regeneration Research 2017年第8期12卷 1322-1328页

作者： Zi-wei Zhou Ya-dan Li Wei-wei Gao Jie-li Chen Shu-yuan Yue Jian-ning Zhang Department of Neurosurgery Tianjin Medical University General Hospital Tianjin China Tianjin Neurological Institute Tianjin China key laboratory of post-trauma Neuro-repair and regeneration in central nervous system Ministry of Education Tianjin China Tianjin key laboratory of Injuries Variations and Regeneration of Nervous System Tianjin China Intensive Care Units Tianjin Huanhu Hospital Tianjin China Department of Neurology Henry Ford Hospital Detroit MI USA

A moderate stress such as cold water swimming can raise the tolerance of the body to potentially injurious events. However, little is known about the mechanism of beneficial effects induced by moderate stress. In this study, we used a classic rat model of traumatic brain injury to test the hypothesis that cold water swimming preconditioning improved the recovery of cognitive functions and explored the mechanisms. Results showed that after traumatic brain injury, pre-conditioned rats（cold water swimming for 3 minutes at 4℃） spent a significantly higher percent of times in the goal quadrant of cold water swim, and escape latencies were shorter than for non-pretreated rats. The number of circulating endothelial progenitor cells was significantly higher in pre-conditioned rats than those without pretreatment at 0, 3, 6 and 24 hours after traumatic brain injury. Immunohistochemical staining and Von Willebrand factor staining demonstrated that the number of CD34~＋ stem cells and new blood vessels in the injured hippocampus tissue increased significantly in pre-conditioned rats. These data suggest that pretreatment with cold water swimming could promote the proliferation of endothelial progenitor cells and angiogenesis in the peripheral blood and hippocampus. It also ameliorated cognitive deficits caused by experimental traumatic brain injury.

关键词： nerve regeneration cold water swimming cognitive deficits endothelial progenitor cells angiogenesis neural repair stress Morriswater maze fluid percussion injury model CD34 Von Willebrand factor neural regeneration

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Bioinformatic identification of key candidate genes and pathways in axon regeneration after spinal cord injury in zebrafish

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Neural regeneration Research 2020年第1期15卷 103-111页

作者： Jia-He Li Zhong-Ju Shi Yan Li Bin Pan Shi-Yang Yuan Lin-Lin Shi Yan Hao Fu-Jiang Cao Shi-Qing Feng Department of Orthopedics Tianjin Medical University General HospitalTianjinChina Department of Orthopedics the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Tianjin Neurological Institute Key Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous SystemMinistry of Education and Tianjin CityTianjinChina

Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord injury,whereas humans *** analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury,and to explore the key genes and pathways of axonal regeneration after spinal cord injury,microarray GSE56842 was analyzed using the online tool,GEO2R,in the Gene Expression Omnibus *** ontology and protein-protein interaction networks were used to analyze the identified differentially expressed ***,we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals.A total of 636 differentially expressed genes were obtained,including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated *** Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained.A protein-protein interaction network contained 480 node genes and 1976 node *** also obtained the 10 hub genes with the highest correlation and the two modules with the highest *** results showed that spectrin may promote axonal regeneration after spinal cord injury in *** growth factor beta signaling may inhibit repair after spinal cord injury in *** adhesion or tight junctions may play an important role in the migration and proliferation of some cells,such as Schwann cells or neural progenitor cells,after spinal cord injury in *** analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish,providing targets for treatment of spinal cord injury in mammals.

关键词： axonal regeneration differentially expressed genes focal adhesions Gene Ontology Kyoto Encyclopedia of Genes and Genomes neural regeneration protein-protein interaction network signaling pathway spectrin tight junctions transforming growth factor beta Wnt signaling pathway

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Antisense MMP-9 RNA inhibits malignant glioma cell growth in vitro and in vivo

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Neuroscience Bulletin 2013年第1期29卷 83-93页

作者： Cuiyun Sun Qian Wang Hongxu Zhou Shizhu Yu Alain R. Simard Chunsheng Kang Yanyan Li Yanling Kong Tongling An Yanjun Wen Fudong Shi Junwei Hao Department of Neuropathology Tianjin Neurological Institute Tianjin Medical University General Hospital key laboratory of post-trauma Neuro-repair and regeneration in the central nervous system Ministry of Education Tianjin key laboratory of Injuries Variations and Regeneration of the Nervous System Département de Chimie et Biochimie Université de Moncton Moncton New Brunswick E1A 3E9 Canada Department of Neurology Tianjin Neurological Institute Tianjin Medical University General Hospital

The matrix-degrading metalloproteinases （MMPs）, particularly MMP-9, play important roles in the pathogenesis and development of malignant gliomas. In the present study, the oncogenic role of MMP-9 in malignant glioma cells was investigated via antisense RNA blockade in vitro and in vivo. TJ905 malignant glioma cells were transfected with pcDNA3.0 vector expressing antisense MMP-9 RNA （pcDNA-AS-MMP9）, which significantly decreased MMP-9 expression, and cell proliferation was assessed. For in vivo studies, U251 cells, a human malignant glioma cell line, were implanted subcutaneously into 4-to 6-week-old BALB/c nude mice. The mice bearing well-established U251 gliomas were treated with intratumoral pcDNA-AS-MMP9-Lipofectamine complex （AS-MMP-9-treated group）, subcutaneous injection of endostatin （endostatin-treated group）, or both （combined therapy group）. Mice treated with pcDNA （empty vector）-Lipofectamine served as the control group. Four or eight weeks later, the volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity were assayed. We demonstrate that pcDNA-AS-MMP9 significantly decreased MMP-9 expression and inhibited glioma cell proliferation. Volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity in the antisense-MMP-9-treated and therapeutic alliance groups were significantly lower than those in the control group. The results suggest that MMP-9 not only promotes malignant glioma cell invasiveness, but also affects tumor cell proliferation. Blocking the expression of MMP-9 with antisense RNA substantially suppresses the malignant phenotype of glioma cells, and thus can be used as an effective therapeutic strategy for malignant gliomas.

关键词： matrix-degrading metalloproteinase 9 antisense MMP-9 RNA cell proliferation malignant glioma cells

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Use of a compact high-definition two-dimensional exoscope in surgical treatment of large vestibular schwannoma

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Chinese Medical Journal 2020年第11期133卷 1292-1297页

作者： Xin Chen Xiang-Liang Gao Yan Chai Ming-Ming Shi Jian-Ning Zhang Shu-Yuan Yue Department of Neurosurgery Tianjin Medical University General HospitalTianjin Neurological InstituteKey Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous SystemMinistry of EducationTianjin Key Laboratory of InjuriesVariations and Regeneration of Nervous SystemTianjin 300052China

Background::Extra-corporeal video telescope operating monitor system provides a necessary instrument to perform high-precision neurosurgical procedures that could substitute or supplement the traditional surgical *** present study was designed to evaluate a compact high-definition two-dimensional exoscope system for assisting in surgical removal of large vestibular schwannoma(VS),as an alternative to a binocular surgical ***::Patients with Koos grade 3 and grade 4 VS undergoing surgery were enrolled in this prospective cohort study between January 2013 and June *** demographics and tumor characteristics(size,Koos grade,composition[cystic or solid mass])were matched between the two groups of *** following outcome measurements were compared between the two groups:duration of surgery,volume of blood loss,extent of tumor resection,number of operating field adjustments,pre-and post-operative facial and cochlear nerve function evaluated at 3 months post-surgery,complications and surgeons’***::A total of 81 patients received tumor resection through the retrosigmoid approach under either an exoscope(cases,n=39)or a surgical microscope(control,n=42).Patients in the two groups had comparable tumor location(P=0.439),Koos grading(P=0.867),and composition(P=0.891).While no significant differences in the duration of surgery(P=0.172),extent of tumor resection(P=0.858),facial function(P=0.838),and hearing ability(P=1.000),patients operated on under an exoscope had less blood loss(P=0.036)and a fewer field adjustments(Psystem provides a safe and efficient means to assist in removing large VSs,as compared to a surgical *** the acquaintance with a visual perception through a dynamic hint and stereoscopically vie

关键词： Vestibular schwannoma Exoscope Telescope video monitor Operating microscope

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