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Two-dimensional gel electrophoresis and surface-enhanced laser desorption ionization-time of flight-mass spectrometry for detection of protein expression profiles in the hippocampus following closed brain injury

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Neural Regeneration Research 2010年第23期5卷 1795-1801页

作者： Qingming Shu Zhiqiang Li Shuwang Yang Lingzhi Li Xiao Bai Yongliang Zhang The Chinese PLA Postgraduate Medical School Beijing 100853 China Department of Pathology General Hospital of Chinese People's Armed Police Forces Beijing 100039 China Second Department of Internal Medicine Inner Mongolia Autonomous Regional Corps Hospital Huhhot 010031 Inner Mongolia Autonomous Region China Postgraduate Division Training Department of Medical College of Chinese People's Armed Police Forces Tianjin 300162 China Department of Pharmacochemistry Medical College of Chinese People's Armed Police Forces Tianjin 300162 China First Division South Building General Hospital of Chinese People's Armed Police Forces Beijing 100039 China Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard Department of Scientific Research Medical College of Chinese People's Armed Police Forces Tianjin 300162 China

Gene expression profile changes in brain regions following traumatic brain injury at the gene level cannot sufficiently elucidate gene expression time, expression amount, protein post-translational processing or modification. Therefore, it is necessary to quantitatively analyze the gene expression profile using proteomic techniques. In the present study, we established a rat model of closed brain injury using Marmarou＇s weight-drop device, and investigated hippocampal differential protein expression using two-dimensional gel electrophoresis and surface-enhanced laser desorption ionization-time of flight-mass spectrometry. A total of 364 protein peaks were detected on weak cation exchange-2 protein chips, including 37 differential protein peaks. 345 protein peaks were detected on immobilized metal affinity capture arrays-Cu, including 12 differential protein peaks Further examination of these differential proteins revealed that glucose-regulated protein and proteasome subunit alpha type 3 expression were significantly upregulated post-injury. These results indicate that brain injury can alter protein expression in the hippocampus, and that glucose-regulated protein and proteasome subunit alpha type 3 are closely associated with the occurrence and development of traumatic brain injury.

关键词： surface-enhanced laser desorption ionization-time of flight-mass spectrometry two-dimensional gel electrophoresis hippocampus proteomics brain injury neural regeneration

Neuronal injury and brain-derived neurotrophic factor expression in a rat model of amygdala kindling seizures Differences in brain regions and kindling courses

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Neural Regeneration Research 2010年第8期5卷 585-590页

作者： Weihong Lin Hongmei Meng Yudan Lv Zan Wang Na Li Li Cui Baimin Zhang Department of Neurology First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina

BACKGROUND：Studies have demonstrated that brain-derived neurotrophic factor （BDNF） has a dual effect on epilepsy. However, the relationship between epilepsy-induced brain injury and BDNF remains poorly understood.OBJECTIVE：According to ultrastructural and molecular parameters, to detect the degree of neuronal injury and BDNF expression changes at different brain regions and different kindling times to determine the effects of BDNF on epilepsy-induced brain injury.DESIGN, TIME AND SETTING：A randomized, controlled, animal experiment based on neuropathology and molecular biology was performed at the Department of Physiology and Department of Pathology, Basic Medical College of Jilin University in 2003.MATERIALS：UltraSensitiveTM SP kit for immunohistochemistry （Fuzhou Maxim Biotechnology, China）, BDNF antibody （concentrated type, Wuhan Boster Biological Technology, China）, JEM-1000SX transmission electron microscopy （JEOL, Japan）, and BH-2 light microscope （Olympus, Japan） were used in the present study.METHODS：Wistar rats were randomly assigned to control （n = 6）, sham-surgery （n = 6）, and model （n = 60） groups. The control group rats were not treated; an electrode was embedded into the amygdala in rats from the sham-surgery and model groups; an amygdala kindling epilepsy model was established in the model group.MAIN OUTCOME MEASURES：Pathological changes in the temporal lobe and hippocampus were observed by light and electron microscopy at 1, 3, 7, 14, and 21 days following kindling, and BDNF expression in the various brain regions was determined by immunohistochemistry.RESULTS：In the model group, temporal lobe cortical and hippocampal neurons were swollen and the nuclei were laterally deviated. There were also some apoptotic neurons 3 days after kindling. The nucleoli disappeared and the nuclei appeared broken or lysed, as well as slight microglia hyperplasia, at 7 days. Electron microscopic observation displayed chromatin aggregation in the nuclei and slight mitochondrion swelling 3 days after kindling. injury cha

关键词： epilepsy brain injury brain-derived neurotrophic factor kindling brain regions rats neuronal injury neural regeneration

Mesenteric lymph reperfusion may exacerbate brain injury in a rat model of superior mesenteric artery occlusion shock

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Neural Regeneration Research 2010年第9期5卷 683-689页

作者： Zigang Zhao Chunyu Niu Aimin Shang Jiaming Tian Rui Han Chunhui Zhang Yuping Zhang Jing Zhang Institution of Microcirculation Department of Pathophysiology Basic Medical College Hebei North University Zhangjiakou 075029 HebeiProvince China

BACKGROUND：The intestinal lymphatic pathway and intestinal ischemia/reperfusion are mainly involved in mesenteric lymph duct ligation or drainage; moreover,intervention by reducing the lymph liquid reflux might relieve lung and other organ dysfunction induced by intestinal ischemia/reperfusion; however,research addressing mesenteric lymph reperfusion （MLR） and brain injury has not yet to be reported.OBJECTIVE：To observe the effect of MLR on brain tissue in a rat model of superior mesenteric artery occlusion （SMAO） shock,and to explore the molecular mechanism of MLR.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment at a neuro-pathophysiology level was performed at the Institute of Microcirculation,Hebei North University; Department of Pathophysiology,Basic Medical College; Department of Pathology,the First Hospital of Hebei North University between December 2007 and March 2009.MATERIALS：Adenosine triphosphate （ATP） standard was provided by the National Institute for the Control of Pharmaceutical and Biological Products; lactic acid （LA）,superoxide dismutase （SOD）,malonaldehyde （MDA）,nitrogen monoxidum （NO）,nitric oxide synthase （NOS）,myeloperoxidase （MPO） and ATPase assay kits were provided by Nanjing Jiancheng Bioengineering Institute,China.METHODS：A total of 24 male Wistar rats were randomly divided into four groups.In the sham-surgery group （n = 6）,both the mesenteric lymph duct and the superior mesenteric artery were not blocked; in the MLR group （n = 6）,the mesenteric lymph duct was occluded for 1 hour followed by 2-hour reperfusion; in the SMAO group （n = 6）,the superior mesenteric artery was occluded for 1 hour followed by 2-hour reperfusion; in the MLR ＋ SMAO group （n = 6）,both the mesenteric lymph duct and superior mesenteric artery were occluded for 1 hour followed by 2-hour reperfusion.MAIN OUTCOME MEASURES：Mean arterial blood pressure prior to and following ischemia/reperfusion; brain tissue morphology levels of LA,MDA,SOD,NO,NOS,MPO,ATPase and ATP following reperfusion.RESULTS：MLR did

关键词： mesenteric lymph reperfusion shock superior mesenteric artery occlusion brain injury neural regeneration

Endogenous adult neurogenesis and cognitive function recovery following traumatic brain injury in the rat hippocampus

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Neural Regeneration Research 2010年第9期5卷 645-650页

作者： Wangmiao Zhao Linchun Huan Yan Zhao Jie Zhao Qi Zhang Lin Zhang Rong Yan Shuyuan Yang Xinyu Yang Department of Neurosurgery Tianjin Medical University General HospitalTianjin Neurology InstituteTianjin Key Laboratory of InjuriesVariations and Regeneration of Nervous SystemTianjin 300052China Department of Neurosurgery General Hospital of Chinese PLA Beijing 100853 China Tianjin People's Hospital Tianjin 300121 China

BACKGROUND：Endogenous neural progenitor cells play a beneficial role for cognitive recovery following traumatic brain injury.However,there are few classification-control studies aimed at varying graded brain trauma.OBJECTIVE：To observe the effects of adult endogenous neurogenesis on cognitive function repair and regeneration of neural progenitor cells following varying graded traumatic hippocampal injury to determine the significance of endogenous neurogenesis in the repair of brain injury.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment was performed at the Key Laboratory of Injuries,Variations and Regeneration of Nervous System,Tianjin Medical University General Hospital,from February to October 2009.MATERIALS：Mouse anti-rat 5-bromodeoxyuridine （BrdU） and neuronal nuclei （NeuN） monoclonal antibodies were purchased from Millipore Corporation,USA.METHODS：A total of 45 Wistar rats were randomly assigned to three groups.Mild and severe injury groups were respectively subjected to （182 ± 2） kPa and （284 ± 4） kPa lateral fluid percussion to establish models of brain injury,and the control group was subjected to surgery with no lateral fluid percussion.MAIN OUTCOME MEASURES：Cognitive function was estimated using the Morris water maze.Proliferation,survival,and differentiation of newly generated cells in the injured hippocampus were observed through the use of immunofluorescent staining.RESULTS：At 7 days post-injury,the number of BrdU＋ cells in the hippocampal dentate gyrus significantly increased in the mild and severe injury groups compared with the control group （P〈0.01）.At 61 days post-injury,the number of BrdU7NeuN＋ cells in the hippocampal dentate gyrus was significantly greater in the mild injury group compared with the severe injury and control groups （P〈 0.01）.In addition,the control group exhibited the greatest proportion of surviving cells that differentiated into mature neurons compared with the injury groups （P〈 0.01）.Moreover,at 61 days post-injury,cognitive function in rats with mild inj

关键词： traumatic brain injury hippocampus Morris water maze neurogenesis cognitive function brain injury neural regeneration

Surgically-induced brain injury:where are we now?

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Chinese Neurosurgical Journal 2020年第1期6卷 45-55页

作者： Travis Zachary D. Sherchan Prativa Hayes William K. Zhang John H. Department of Earth and Biological Sciences School of MedicineLoma Linda UniversityLoma LindaCA 92354USA Department of Physiology and Pharmacology School of MedicineLoma Linda UniversityLoma LindaCA 92354USA Department of Anesthesiology School of MedicineLoma Linda UniversityLoma LindaCA 92354USA

Neurosurgical procedures cause inevitable brain damage from the multitude of surgical manipulations utilized.Incisions,retraction,thermal damage from electrocautery,and intraoperative hemorrhage cause immediate and long-term brain injuries that are directly linked to neurosurgical operations,and these types of injuries,collectively,have been termed surgical brain injury(SBI).For the past decade,a model developed to study the underlying brain pathologies resulting from SBI has provided insight on cellular mechanisms and potential therapeutic targets.This model,as seen in a rat,mouse,and rabbit,mimics a neurosurgical operation and causes commonly encountered post-operative complications such as brain edema,neuroinflammation,and hemorrhage.In this review,we elaborate on SBI and its clinical impact,the SBI animal models and their clinical relevance,the importance of applying therapeutics before neurosurgical procedures(i.e.,preconditioning),and the new direction of applying venom-derived proteins to attenuate SBI.

关键词： brain injury Cerebral edema Preconditioning Neurotherapeutics Venom therapies

Acupuncture-induced oxygen therapy inhibits oxyradical injury and improves microcirculation following brain injury

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Neural Regeneration Research 2010年第6期5卷 439-444页

作者： Huafeng Yang Zhanwen Li Guojun Shi Xuanlei Ren Ximin Yang Department of Neurosurgery Ningbo Women and Children's Hospital Ningbo 315012 Zhejiang Province China College of Traditional Chinese Medicine Southern Medical University Guangzhou 510515 Guangdong Province China Department of Hepatobiliary Surgery Nanfang HospitalSouthern Medical UniversityGuangzhou 510515 Guangdong Province China Laboratory Center Third Hospital of Chinese PLA Baoji 721004 Shaanxi Province China

BACKGROUND： Acupuncture-induced oxygen therapy combines acupoint theory in traditional Chinese medicine and modern oxygen therapy. Clinical studies have shown that acupuncture-induced oxygen therapy results in favorable outcomes for brain injury. However, the mechanisms of action remain poorly understood. OBJECTIVE： To determine pathological changes and malondialdehyde （MDA） content, superoxide dismutase （SOD） and nitric oxide synthase （NOS） activity, as well as hemorheological brain alterations following acupuncture-induced oxygen therapy, and to explore possible mechanisms of acupuncture-induced oxygen therapy on brain injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Animal Experimental Center of Xi＇an Medical University from January 2006 to April 2009. MATERIALS： An oxygen delivery device, through the use of acupuncture （oxygen delivery machine ＋ silver hollowed needle, 0.5 mm inner diameter）, was purchased from Research Center ol Machine, Shaanxi University of Science and Technology in China. METHODS： A total of 180 Sprague Dawley rats were randomly assigned to six groups （n = 30）： normal, sham-surgery （dura mater exposure）, model （brain injury induced by free-falling of heavy object to head）, Xiantaimixture （0.417 mL/100 g following brain injury）, electroacupuncture [acupuncture at Baihui （DU 20）, Housanfi （ST 36）, Yanglingquan （GB 34）, and Sanyinjiao （SP 6） following brain injury], and acupuncture-induced oxygen therapy （oxygen delivery through hollowed needle to Baihui （DU 20）, Housanfi （ST 36）, Yanglingquan （GB 34）, and Sanyinjiao （SP 6） following brain injury, 0.01 mL/minute）. Group intervention was performed once a day for 14 consecutive days. MAIN OUTCOME MEASURES： Pathological changes, MDA content, SOD and NOS activity, and hemorheological alterations in the brain. RESULTS： Obvious pathological changes were observed, such as hemorrhage, edema, and cell necrosis, following brain injury. These alterations were significantly improved following 14 days of

关键词： oxygen therapy acupuncture brain injury malondialdehyde superoxide dismutase nitdc oxide synthase hemorheological index

Weak cation exchange 2 protein chip for detecting differentially expressed brainstem proteins in a rat model of closed traumatic brain injury

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Neural Regeneration Research 2010年第5期5卷 372-377页

作者： Lin Liang Haiying Gong Li Zhan Shuwang Yang Yongliang Zhang Training Department Graduate Division Tianjin Key Laboratory for Biomarker of Occupational and Environmental Hazard Medical College of Chinese People's Armed Police Force Tianjin 300162 China Medicinal Chemistry Department Medical College of Chinese People's Armed Police Force Tianjin 300162 China Research Department Medical College of Chinese People's Armed Police Force Tianjin 300162 China

BACKGROUND： Studies have reported the combined use of two-dimensional gel electrophoresis and mass spectrometry to detect differentially expressed proteins in the rat brainstem following brain injury. However, the detected differential proteins often exhibit low sensitivity and high relative molecular weight. Although protein chip technology is thought to compensate for these inadequacies, no related studies or results have been reported. OBJECTIVE： To propose the application of weak cation exchange protein chips in combination with mass spectrometry for determining protein expression profiles and characteristics in the brainstem following closed brain injury. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiments utilizing proteomics were performed from June 2007 to December 2008 in the Proteomics Laboratory, Medical College of Chinese People＇s Armed Police Force. MATERIALS： Weak cation exchange 2 protein chip, Ciphergen Proteinchip System （PBS-IIC）. METHODS： A total of 72 rats were randomly assigned to two groups： sham-surgery （n = 12） and injury （n = 60）. A closed traumatic brain injury model caused by falling object was replicated in the injury group, which was then subdivided into five subgroups according to different time points after injury： 4, 8, 12, 24, and 48 hours, with 12 rats in each subgroup. In the sham-surgery group, only the skin was removed and the stainless steel pad was fixed to the skull. MAIN OUTCOME MEASURES： The brain injury rats were sacrificed at 4, 8, 12, 24, and 48 hours after injury, respectively, and the control rats were sacrificed at 24 hours. Pathological changes in the brainstem were determined using hematoxylin-eosin staining, and differential protein expression in the brainstem was detected using a weak cation exchange 2 protein chip and protein chip reader. RESULTS： In the sham-surgery group, cells appeared normal. However, in the brain injury group, some brainstem neurons exhibited pyknosis, with reduced numbers of Nissl bodies in the cytoplasm swollen cell bodi

关键词： protein chip ion exchange brain injury brainstem rats proteomics neural regeneration

brain injury Biomechanics and Abusive Head Trauma

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Journal of Forensic Science and Medicine 2018年第2期4卷 91-100页

作者： Rudy J Castellani Carl J Schmidt Center for Neuropathology Western Michigan University Homer Stryker MD School of MedicineKalamazoo Department of Pathology University of Maryland School of MedicineBaltimoreMDUSA Department of Pathology University of MichiganAnn ArborMichigan

Contemporary biomechanical theory of traumatic brain injury has its foundation in Holbourn’s thesis on shear strain and Ommaya’s primate experimentation demonstrating the role of rotation in a variety of lesions including subdural hematoma(SDH)and diffuse axonal injury.Empirical human observations have since confirmed,for the most part,the early concepts.Ethical concerns regarding primate research,however,have prompted in vitro models,which in turn has led to challenges with respect to the correlation between in vitro observations and the clinical data.Despite these challenges,medicolegal proceedings may call upon biomechanical engineers to reconstruct complex injury scenarios and offer opinions on the scientific plausibility of clinical disease states,such as SDH,hemorrhagic retinopathy,and cerebral edema,associated with hypothetical or proffered action sequences during the course of an unwitnessed homicide.It is important to note,however,that in vitro models by their nature are low‑evidence quality studies that attempt to advance hypotheses but do not address cause and effect.As a whole,biomechanical models,as they pertain specifically to the brain and spine,are mathematically imprecise.Often,endpoints of limited relevance are relied upon(e.g.,skull fracture thresholds),which predictably overestimate the in vivo risk of significant injury.Given the increasing role of biomechanical engineering in the interpretation of fatal pediatric head trauma,a heightened awareness of the limitations warranted.

关键词： Abusive head trauma biomechanics brain injury impact subdural hematoma

Correlating learning and memory improvements to long-term potentiation in patients with brain injury

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Neural Regeneration Research 2008年第2期3卷 172-176页

作者： Xingfu Peng Qian Yu Department of Rehabilitation Medicine Affiliated Hospital of Luzhou Medical College Luzhou 646000 Sichuan Province China

BACKGROUND： brain injury patients often exhibit learning and memory functional deficits. Long-term potentiation （LTP） is a representative index for studying learning and memory cellular models; the LTP index correlates to neural plasticity. OBJECTIVE： This study was designed to investigate correlations of learning and memory functions to LTP in brain injury patients, and to summarize the research advancements in mechanisms underlying brain functional improvements after rehabilitation intervention. RETRIEVAL STRATEGY： Using the terms ＂brain injuries, rehabilitation, learning and memory, long-term potentiation＂, manuscripts that were published from 2000-2007 were retrieved from the PubMed database. At the same time, manuscripts published from 2000-2007 were also retrieved from the Database of Chinese Scientific and Technical Periodicals with the same terms in the Chinese language. A total of 64 manuscripts were obtained and primarily screened. Inclusion criteria： studies on learning and memory, as well as LTP in brain injury patients, and studies focused on the effects of rehabilitation intervention on the two indices; studies that were recently published or in high-impact journals. Exclusion criteria： repetitive studies. LITERATURE EVALUATION： The included manuscripts primarily focused on correlations between learning and memory and LTP, the effects of brain injury on learning and memory, as well as LTP, and the effects of rehabilitation intervention on learning and memory after brain injury. The included 39 manuscripts were clinical, basic experimental, or review studies. DATA SYNTHESIS： Learning and memory closely correlates to LTP. The neurobiological basis of learning and memory is central nervous system plasticity, which involves neural networks, neural circuits, and synaptic connections, in particular, synaptic plasticity. LTP is considered to be an ideal model for studying synaptic plasticity, and it is also a classic model for studying neural plasticity of learning and memory. brain injury patients c

关键词： learning and memory brain injury long-term potentiation rehabilitation