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Neural Regeneration Research 2010年第18期5卷 1408-1412页

作者： Huanmin Gao Ling Wang Yunliang Guo Department of Neurology Second Affiliated Hospital Qingdao University Medical College Qingdao 266042 Shandong Province China Shandong Province Key Laboratory of brain Disease Prevention and Treatment Institute of Cerebral Vascular Diseases of Qingdao University Medical College Qingdao 266003 Shandong Province China

Acupuncture has recently gained popularity in many countries as an alternative and complementary therapeutic intervention. Previous studies have shown that changes in genes, proteins, and their metabolites were measureable during acupuncture for treatment of cerebral ischemia. Through the use of in situ hybridization and immunohistochemistry, the present study confirmed that electroacupuncture increased insulin-like growth factor-1 mRNA and protein expression in the corpus stfiatum following cerebral ischemia, reduced brain edema following middle cerebral artery occlusion reperfusion, and decreased infarct volume. Results suggested that electroacupuncture is effective in the relief of cerebral ischemia by increasing endogenous insulin-like growth factor-1 expression.

关键词： electroacupuncture cerebral ischemia focal insulin-like growth factor-1 brain injury neural regeneration

Induced arousal following zolpidem treatment in a vegetative state after brain injury in 7 cases Analysis using visual single photon emission computerized tomography and digitized cerebral state monitor

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Neural Regeneration Research 2008年第1期3卷 94-96页

作者： Bo Du Aijun Shan Di Yang Wei Xiang Department of Neurosurgery Second Affiliated Hospital of Jinan University （Shenzhen People＇s Hospital） Shenzhen 518020 GuangdongProvince China

BACKGROUND： Several studies have reported the use of zolpidem for induced arousal after permanent vegetative states. However, changes in brain function and EMG after zolpidem treatment requires further investigation. OBJECTIVE： To investigate the effect of zolpidem, an unconventional drug, on inducing arousal in patients in a permanent vegetative state after brain injury using visual single photon emission computerized tomography and digitized cerebral state monitor. DESIGN： A self-controlled observation. SETTING： Shenzhen People＇s Hospital. PARTICIPANTS： Seven patients in a permanent vegetative state were selected from the Department of Neurosurgery, Shenzhen People＇s Hospital from March 2005 to May 2007. The group included 5 males and 2 females, 24-55 years of age, with a mean age of 38.5 years. All seven patients had been in a permanent vegetative statement for at least six months. The patient group included three comatose patients, who had sustained injuries to the cerebral cortex, basal ganglia, or thalamus in motor vehicle accidents, and four patients, who had suffered primary/secondary brain stem injury. Informed consents were obtained from the patients＇ relatives. METHODS： The patients brains were imaged by ^99Tc^m ECD single photon emission computerized tomography prior to treatment with zolpidem [Sanofi Winthrop Industrie, France, code number approved by the State Food ＆ Drug Administration （SFDA） J20040033, specification 10 mg per tablet. At 8：00 p.m., 10 mg zolpidem was dissolved with distilled water and administered through a nasogastric tube at 1 hour before and after treatment and 1 week following treatment, respectively. Visual analysis of cerebral perfusion changes in the injured brain regions before and after treatment was performed. Simultaneously, three monitoring parameters were obtained though a cerebral state monitor, which included cerebral state index, electromyographic index, and burst suppression index. MAIN OUTCOME MEASURES： Comparison of the three brain function indices, cerebral perf

关键词： brain injury controlled clinical trials coma

Two-dimensional electrophoretogram of acute brain injury-associated proteins Comparison between injured and normal cerebral cortex

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Neural Regeneration Research 2008年第2期3卷 182-186页

作者： Xuejun Li Xianrui Yuan Cui Li Zefeng Peng Dun Yuan Department of Neurosurgery Xiangya Hospital Central South University Changsha 410008 Hunan Province China Key Laboratory of Cancer Proteomics of Chinese Ministry of Health Xiangya Hospital Central South University Changsha 410008 Hunan Province China

BACKGROUND： To this date, specific molecular markers for early diagnosis and prognosis monitoring of craniocerebral injury in clinical medicine do not exist. Therefore, differential detection of specific proteins might play an important role in diagnosis and treatment of this type of brain injury. OBJECTIVE： To compare differential cerebral cortical protein expression of craniocerebral injury patients and normal subjects through the use of proteomics. DESIGN： Contrast observation. SETTING： Department of Neurosurgery, Xiangya Hospital of Central South University. PARTICIPANTS： Ten patients （6 males and 4 females, 20 58 years old）, with severe craniocerebral injury, were selected at the Department of Neurosurgery, Xiangya Hospital of Central South University, from June 2004 to December 2006. All patients were diagnosed with CT test and Glasgow test （scores 〈 8）. Surgery was performed 4-12 hours after craniocerebral injury, and injured cortical tissues of the frontal and temporal lobes were resected for sampling. At the same time, control cortical tissues were collected from frontal and temporal lobes of 2 epileptic patients who underwent hippocampus-nucleus amygdala resection, and 2 lateral ventricular tumor patients who underwent tumor resection. The participants and their relatives provided confirmed consent, and this study received confirrned consent from the local ethics committee. METHODS： Ten samples from injured patients and 4 normal samples were compared through the use of proteomics. Total protein was separated by using two-dimensional electrophoresis with immobilized pH gradients, and the differential protein expressions were compared using image analysis after blue-sliver staining. Differential protein spot expressions were analyzed with a matrix-assisted laser desorption/ionization time of flight mass spectrometry （MALDI/TOF MS） and electrospray ionization-quadrupole time of flight mass spectrometry （ESI-Qq TOF MS）. MAIN OUTCOME MEASURES：① Two-dimensional electrophoresis of protein from cere

关键词： brain injury cortical tissue proteomics two-dimensional gel electrophoresis mass spectrometry

Electroacupuncture reduces injury to the blood-brain barrier following cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2012年第36期7卷 2901-2906页

作者： Yongjun Peng Hesheng Wang Jianhua Sun Li Chen Meijuan Xu Jihong Chu Department of Acupuncture and Rehabilitation Affiliated Hospital of Nanjing University of Chinese Medicine

This study used electroacupuncture at Renzhong （DU26） and Baihui （DU20） in a rat model of cerebral ischemia/reperfusion injury. Neurological deficit scores, western blotting, and reverse transcription-PCR results demonstrated that electroacupuncture markedly reduced neurological deficits, decreased corpus striatum aquaporin-4 protein and mRNA expression, and relieved damage to the blood-brain barrier in a rat model of cerebral ischemia/reperfusion injury. These results suggest that electroacupuncture most likely protects the blood-brain barrier by regulating aquaporin-4 expression following cerebral ischemia/reperfusion injury.

关键词： electroacupuncture cerebral ischemia/reperfusion blood-brain barrier aquaporin-4 brain edema rat Renzhong （DU26） Baihui （DU20） brain injury regeneration neural regeneration

Effects of propofol on neuronal apoptosis and aquaporin-4 expression in a rat model of traumatic brain injury

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Neural Regeneration Research 2008年第9期3卷 975-978页

作者： Jianfang Song Xiangyu Ji Zangong Zhou Department of Anesthesiology Affiliated Hospital of Qingdao University Medical College Qingdao 266003 Shandong Province China

BACKGROUND： Several studies have demonstrated that propofol exhibits protective effects in the central nervous system. OBJECTIVE： To observe the effects of propofol on neuronal apoptosis and aquaporin-4 （AQP-4） expression in a rat model of traumatic brain injury and to further investigate the mechanisms of action. DESIGN, TIME AND SETTING： The present neuronal, pathomorphological experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical College between April 2007 and March 2008. MATERIALS： Traumatic brain injury was induced by free falling objects in 150 healthy, male, Wistar rats. Propofol was produced by AstraZeneca, China. Rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemistry kit, and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling （TUNEL） kit were purchased from Wuhan Boster Bioengineering Co., Ltd., China. METHODS： All 150 rats were randomly and evenly divided into lesion-only and propofol-treated groups. One hour after traumatic brain injury, propofol-treated animals received 1% propofol （10 mg/kg） through the caudal vein, followed by a sustained perfusion of 30 mg/kg propofol per hour for 2 hours, while the lesion-only group received equal volumes of physiological saline in parallel. MAIN OUTCOME MEASURES： At 6, 12, 24, 48, and 72 hours after traumatic brain injury, morphological changes in the peritraumatic and adjacent brain areas were analyzed in all rats by hematoxylin-eosin （HE） staining. In addition, cellular apoptosis was detected by TUNEL assay and the number of AQP-4-positive cells was determined by immunohistochemistry techniques. brain water content was calculated as the ratio of dry to wet tissue weight. RESULTS： HE staining results demonstrated that, in the lesion-only group, the peritraumatic area exhibited neuronal and glial cell necrosis and disintegration. The adjacent area displayed swollen neuronal perikarya and vascular endothelial ceils, cellular edema, and a small amount of proliferating glial ceils. In

关键词： apoptosis aquaporin-4 brain injury propofol

Puerarin protects brain tissue against cerebral ischemia/reperfusion injury by inhibiting the inflammatory response

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Neural Regeneration Research 2014年第23期9卷 2074-2080页

作者： Feng Zhou Liang Wang Panpan Liu Weiwei Hu Xiangdong Zhu Hong Shen Yuanyuan Yao Department of Neurosurgery Second Affiliated Hospital School of Medicine Zhejiang University Medical College Ningbo University Department of Anesthesiology Second Affiliated Hospital School of Medicine Zhejiang University

Puerarin, a traditional Chinese medicine, exerts a powerful neuroprotective effect in cerebral ischemia/reperfusion injury, but its mechanism is unknown. Here, we established rat models of middle cerebral artery ischemia/reperfusion injury using the suture method. Puerarin （100 mg/kg） was administered intraperitoneally 30 minutes before middle cerebral artery occlusion and 8 hours after reperfusion. Twenty-four hours after reperfusion, we found that puerarin significantly improved neurological deficit, reduced infarct size and brain water content, and notably diminished the expression of Toll-like receptor-4, myeloid differentiation factor 88, nuclear factor kappa B and tumor necrosis factor-α in the ischemic region. These data indicate that puerarin exerts an anti-inflammatory protective effect on brain tissue with ischemia/reperfusion damage by downregulating the expression of multiple inflammatory factors.

关键词： nerve regeneration brain injury puerarin cerebral ischemia reperfusion injury rats inflammatory reaction Toll-like receptor-4 nuclear factor kappa B myeloid differentiation factor 88 tumor necrosis factor-α middle cerebral artery occlusion neural regeneration

Does closure of acid-sensing ion channels reduce ischemia/reperfusion injury in the rat brain?

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Neural Regeneration Research 2013年第13期8卷 1169-1179页

作者： Jie Wang Yinghui Xu Zhigang Lian Jian Zhang Tingzhun Zhu Mengkao Li Yi Wei Bin Dong Department of Neurosurgery the First Affiliated Hospital of Dalian Medical University

Acidosis is a common characteristic of brain damage. Because studies have shown that permeable Ca2＋-acid-sensing ion channels can mediate the toxic effects of calcium ions, they have become new targets against pain and various intracranial diseases. However, the mechanism associated with expression of these channels remains unclear. This study sought to observe the expression characteristics of permeable Ca2＋-acid-sensing ion channels during different reperfusion inflows in rats after cerebral ischemia. The rat models were randomly divided into three groups： adaptive ischemia/reperfusion group, one-time ischemia/reperfusion group, and severe cerebral ischemic injury group. Western blot assays and immunofluorescence staining results exhibited that when compared with the one-time ischemia/reperfusion group, acid-sensing ion channel 3 and Bcl-x/I expression decreased in the adaptive ischemia/reperfusion group. Calmodulin expression was lowest in the adaptive ischemia/reperfusion group. Following adaptive reperfusion, common carotid artery flow was close to normal, and the pH value improved. Results verified that adaptive reperfusion following cerebral ischemia can suppress acid-sensing ion channel 3 expression, significantly reduce Ca2＋ influx, inhibit calcium overload, and diminish Ca2＋ toxicity. The effects of adaptive ischemia/reperfusion on suppressing cell apoptosis and relieving brain damage were better than that of one-time ischemia/reperfusion.

关键词： neural regeneration brain injury acid-sensing ion channel 3 cerebral ischemia reperfusion apoptosis calmodulin calcium overload nerve cells grants-supported paper neuroregeneration

Expression of netrin-1 and its receptors, deleted in colorectal cancer and uncoordinated locomotion-5 homolog B, in rat brain following focal cerebral ischemia reperfusion injury

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Neural Regeneration Research 2013年第1期8卷 64-69页

作者： Xiaodan Wang Jinming Xu Jieqin Gong Hui Shen Xiaoping Wang Department of Neurology Shanghai First People's Hospital Shanghai Jiao Tong University School of Medicine Department of Neurology Suzhou Kowloon Hospital Shanghai Jiao Tong University School of Medicine

Netrin-1 is currently one of the most highly studied axon guidance factors. Netrin-1 is widely expressed in the embryonic central nervous system, and together with the deleted in colorectal cancer and uncoordinated locomotion-5 homolog B receptors, netrin-1 plays a guiding role in the construction of neural conduction pathways and the directional migration of neuronal cells. In this study, we established a rat middle cerebral artery ischemia reperfusion model using the intraluminal thread technique. Immunofluorescence microscopy showed that the expression of netrin-1 and deleted in colorectal cancer in the ischemic penumbra was upregulated at 1 day after reperfusion, reached a peak at 14 days, and decreased at 21 days. There was no obvious change in the expression of uncoordinated locomotion-5 homolog B during this time period. Double immunofluorescence labeling revealed that netrin-1 was expressed in neuronal cells and around small vessels, but not in astrocytes and microglia, while deleted in colorectal cancer was localized in the cell membranes and protrusions of neurons and astrocytes. Our experimental findings indicate that netrin-1 may be involved in post-ischemic repair and neuronal protection via deleted in colorectal cancer receptors.

关键词： neural regeneration brain injury cerebral ischemia and reperfusion netrin-1 uncoordinatedlocomotion-5 homolog B deleted in colorectal cancer neuron brain injury grant-supported paper photographs-containing paper neuroregeneration

Acupuncture activates signal transduction pathways related to brain-tissue restoration after ischemic injury

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Neural Regeneration Research 2012年第24期7卷 1866-1872页

作者： Haomei Tian Hong Zhang Junbao Zhu Juan Zhang Hening Cai Yuchen Zhang Chutao Chen Key Laboratory of Meridians and Viscera Hunan University of Traditional Chinese MedicineChangsha 410007Hunan ProvinceChina Liuzhou Hospital of Traditional Chinese Medicine Liuzhou 545001Guangxi Zhuang Autonomous RegionChina Ningxiang Hospital of Traditional Chinese Medicine Ningxiang 410600Hunan ProvinceChina Postgraduate College Hunan University of Traditional Chinese MedicineChangsha 410007Hunan ProvinceChina Laboratory of Acupuncture Bioinformatics Hunan University of Traditional Chinese MedicineChangsha 410007Hunan ProvinceChina

A middle cerebral artery occlusion-model was established in rats using the improved thread embolism method.Rats were treated with acupuncture at either Dazhui（DU14）,Renzhong（DU26）, Baihui（DU20）,or a non-meridian point.Detection with protein-chip technology showed that the level of protein phosphorylation in both groups was upregulated or downregulated depending on the signaling pathway compared with the model group that did not receive acupuncture.Analysis of proteins showing downregulated phosphorylation revealed that five signaling pathways were activated in the acupuncture-treatment group,while only two were activated in the acupuncture-control group.In contrast,analysis of proteins showing upregulated phosphorylation revealed only one pathway was activated in the acupuncture-treatment group,whereas four pathways were activated in the acupuncture-control group.Furthermore,the number of activated proteins in the acupuncture-treatment group was not only higher than the acupuncture-control group,but unlike the acupuncture-control group,the majority of activated proteins were key proteins in the signaling pathways.Our findings indicate that acupuncture at specific points can activate multiple signaling pathways to promote the restoration of brain tissue following ischemic injury,and that this is based on a combination of effects resulting from multiple pathways,targets,and means.

关键词： acupuncture cerebral ischemia Dazhui Baihui Renzhong protein-chip technology signal-transduction pathways nerve injury brain injury ischemic injury neural regeneration

Growth-associated protein 43 and neural cell adhesion molecule expression following bone marrow-derived mesenchymal stem cell transplantation in a rat model of ischemic brain injury

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Neural Regeneration Research 2010年第13期5卷 975-980页

作者： Yu Peng Qimei Zhang Hui You Weihua Zhuang Ying Zhang Chengyan Li Department of Neurology First Clinical College China Three Gorges University Yichang 443003 Hubei Province China Digest Division First Clinical College China Three Gorges University Yichang 443003 Hubei Province China Department of Neurology Renmin Hospital of Wuhan University Wuhan 430060 Hubei Province China

BACKGROUND： Transplantation of bone marrow-derived mesenchymal stem cells （BMSCs） improves motor functional recovery, but the mechanisms remain unclear. OBJECTIVE： To investigate expression of growth-associated protein 43 （GAP-43） and neural cell adhesion molecule following BMSC transplantation to the lateral ventricle in rats with acute focal cerebral ischemic brain damage. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment using immunohistochemistry was performed at the laboratories of Department of Neurology, Renmin Hospital of Wuhan University and Doctoral Scientific Research Work Station of C-BONS PHARMA, Hubei Province, China, from January 2007 to December 2008. MATERIALS： Monoclonal mouse anti-rat 5-bromo-2-deoxyuridine and neural cell adhesion molecule antibodies were purchased from Sigma, USA; monoclonal mouse anti-rat GAP-43 antibody was purchased from Wuhan Boster, China. METHODS： Rat models of right middle cerebral artery occlusion were established using the thread method. At 1 day after middle cerebral artery occlusion, 20μL culture solution, containing 5×10^5 BMSCs, was transplanted to the left lateral ventricle using micro-injection. MAIN OUTCOME MEASURES： Scores of neurological impairment were measured to assess neural function. Expression of GAP-43 and neural cell adhesion molecule at the lesion areas was examined by immunohistochemistry. RESULTS： GAP-43 and neural cell adhesion molecule expression was low in brain tissues of the sham-operated group, but expression increased at the ischemic boundary （P 〈 0.05）. Transplantation of BMSCs further enhanced expression of GAP-43 and neural cell adhesion molecule （P 〈 0.05） and remarkably improved neurological impairment of ischemic rats （P 〈 0.05）. CONCLUSION： BMSC transplantation promoted neurological recovery in rats by upregulating expression of GAP-43 and neural cell adhesion molecule.

关键词： growth-associated protein 43 neural cell adhesion molecule bone marrow-derived mesenchymal stem cell brain injury neural regeneration