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| 1 | Are newborn rat-derived neural stem cells more sensitive to lead neurotoxicity?显示文摘Lead ion (Pb(2+) ) has been proven to be a neurotoxin due to its neurotoxicity on mammalian nervous system, especially for the developing brains of juveniles. However, many reported studies involved the negative effects of Pb(2+) on adult neural cells of humans or other mammals, only few of which have examined the effects of Pb(2+) on neural stem cells. The purpose of this study was to reveal the biological effects of Pb(2+) from lead acetate [Pb (CH 3 COO) 2 ] on viability, proliferation and differentiation of neural stem cells derived from the hippocampus of newborn rats aged 7 days and adult rats aged 90 days, respectively. This study was carried out in three parts. In the first part, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT viability assay) was used to detect the effects of Pb(2+) on the cell viability of passage 2 hippocampal neural stem cells after 48-hour exposure to 0-200 μM Pb(2+) . In the second part, 10 μM bromodeoxyuridine was added into the culture medium of passage 2 hippocampal neural stem cells after 48-hour exposure to 0- 200 μM Pb(2+) , followed by immunocytochemical staining with anti-bromodeoxyuridine to demonstrate the effects of Pb(2+) on cell proliferation. In the last part, passage 2 hippocampal neural stem cells were allowed to grow in the differentiation medium with 0-200 μM Pb(2+) . Immunocytochemical staining with anti-microtubule-associated protein 2 (a neuron marker), anti-glial fibrillary acidic protein (an astrocyte marker), and anti-RIP (an oligodendrocyte marker) was performed to detect the differentiation commitment of affected neural stem cells after 6 days. The data showed that Pb(2+) inhibited not only the viability and proliferation of rat hippocampal neural stem cells, but also their neuronal and oligodendrocyte differentiation in vitro. Moreover, increased activity of astrocyte differentiation of hippocampal neural stem cells from both newborn and adult rats was observed after exposure to high concentration of lead ion in vitro. These findings suggest that hippocampal neural stem cells of newborn rats were more sensitive than those from adult rats to Pb(2+) cytotoxicity. | Yan Ho Chan Mingyong Gao Wutian Wu | 2013 | Neural Regeneration Research2013，8，7： | 14 |
| 2 | SARS-CoV-2 infects human neural progenitor cells and brain organoids显示文摘Dear Editor,Coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)1 has resulted in over 13 million confirmed cases and more than 580,045 deaths across 218 countries and geographical regions as of July 16,2020.This novel coronavirus primarily causes respiratory illness with clinical manifestations largely resembling those of SARS.However,neurological symptoms including headache,anosmia,ageusia,confusion,seizure,and encephalopathy have also been frequently reported in COVID-19 patients. | Bao-Zhong Zhang Hin Chu Shuo Han Huiping Shuai Jian Deng Ye-fan Hu Hua-rui Gong Andrew Chak-Yiu Lee Zijiao Zou Thomas Yau Wutian Wu Ivan Fan-Ngai Hung Jasper Fuk-Woo Chan Kwok-Yung Yuen Jian-Dong Huang | 2020 | Cell Research2020，30，10： | 8 |
| 3 | Functional self-assembling peptide nanofiber hydrogel for peripheral nerve regeneration显示文摘Peripheral nerves are fragile and easily damaged,usually resulting in nervous tissue loss,motor and sensory function loss.Advances in neuroscience and engineering have been significantly contributing to bridge the damage nerve and create permissive environment for axonal regrowth across lesions.We have successfully designed two self-assembling peptides by modifying RADA 16-I with two functional motifs IKVAV and RGD.Nanofiber hydrogel formed when combing the two neutral solutions together,defined as RADA 16-Mix that overcomes the main drawback of RADA16-I associated with low pH.In the present study,we transplanted the RADA 16-Mix hydrogel into the transected rat sciatic nerve gap and effect on axonal regeneration was examined and compared with the traditional RADA16-I hydrogel.The regenerated nerves were found to grow along the walls of the large cavities formed in the graft of RADA16-I hydrogel,while the nerves grew into the RADA 16-Mix hydrogel toward distal position.RADA 16-Mix hydrogel induced more axons regeneration and Schwann cells immigration than RADA16-I hydrogel,resulting in better functional recovery as determined by the gait-stance duration percentage and the formation of new neuromuscular junction structures.Therefore,our results indicated that the functional SAP RADA16-Mix nanofibrous hydrogel provided a better environment for peripheral nerve regeneration than RADA16-I hydrogel and could be potentially used in peripheral nerve injury repair. | Xiaoli Wu Liumin He Wen Li Heng Li Wai-Man Wong Seeram Ramakrishna Wutian Wu | 2017 | Regenerative Biomaterials2017，4，1： | 6 |
| 4 | A novel artificial nerve graft for repairing longdistance sciatic nerve defects:a self-assembling peptide nanofiber scaffold-containing poly (lactic-co-glycolic acid) conduit显示文摘In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold(SAPNS)-containing poly(lactic-co-glycolic acid)(PLGA) conduit(SPC) and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury. | Xianghai Wang Mengjie Pan Jinkun Wen Yinjuan Tang Audra D.Hamilton Yuanyuan Li Changhui Qian Zhongying Liu Wutian Wu Jiasong Guo | 2014 | Neural Regeneration Research2014，9，24： | 5 |
| 5 | Surgical intervention combined with weight-bearing walking training improves neurological recoveries in 320 patients with clinically complete spinal cord injury:a prospective self-controlled study显示文摘Although a large number of trials in the SCI field have been conducted,few proven gains have been realized for patients.In the present study,we determined the efficacy of a novel combination treatment involving surgical intervention and long-term weight-bearing walking training in spinal cord injury(SCI)subjects clinically diagnosed as complete or American Spinal Injury Association Impairment Scale(AIS)Class A(AIS-A).A total of 320 clinically complete SCI subjects(271 male and 49 female),aged 16–60 years,received early(≤7 days,n=201)or delayed(8–30 days,n=119)surgical interventions to reduce intraspinal or intramedullary pressure.Fifteen days post-surgery,all subjects received a weight-bearing walking training with the“Kunming Locomotion Training Program(KLTP)”for a duration of 6 months.The neurological deficit and recovery were assessed using the AIS scale and a 10-point Kunming Locomotor Scale(KLS).We found that surgical intervention significantly improved AIS scores measured at 15 days post-surgery as compared to the pre-surgery baseline scores.Significant improvement of AIS scores was detected at 3 and 6 months and the KLS further showed significant improvements between all pair-wise comparisons of time points of 15 days,3 or 6 months indicating continued improvement in walking scores during the 6-month period.In conclusion,combining surgical intervention within 1 month post-injury and weight-bearing locomotor training promoted continued and statistically significant neurological recoveries in subjects with clinically complete SCI,which generally shows little clinical recovery within the first year after injury and most are permanently disabled.This study was approved by the Science and Research Committee of Kunming General Hospital of PLA and Kunming Tongren Hospital,China and registered at ClinicalTrials.gov(Identifier:NCT04034108)on July 26,2019. | Yansheng Liu Jia-Xin Xie Fang Niu Zhexi Xu Pengju Tan Caihong Shen Hongkun Gao Song Liu Zhengwen Ma Kwok-Fai So Wutian Wu Chen Chen Sujuan Gao Xiao-Ming Xu Hui Zhu | 2021 | Neural Regeneration Research2021，16，5： | 3 |
| 6 | ISP and PAP4 peptides promote motor functional recovery after peripheral nerve injury显示文摘Both intracellular sigma peptide(ISP) and phosphatase and tensin homolog agonist protein(PAP4) promote nerve regeneration and motor functional recovery after spinal cord injury. However, the role of these two small peptides in peripheral nerve injury remains unclear. A rat model of brachial plexus injury was established by crush of the C6 ventral root. The rats were then treated with subcutaneous injection of PAP4(497 μg/d, twice per day) or ISP(11 μg/d, once per day) near the injury site for 21 successive days. After ISP and PAP treatment, the survival of motoneurons was increased, the number of regenerated axons and neuromuscular junctions was increased, muscle atrophy was reduced, the electrical response of the motor units was enhanced and the motor function of the injured upper limbs was greatly improved in rats with brachial plexus injury. These findings suggest that ISP and PAP4 promote the recovery of motor function after peripheral nerve injury in rats. The animal care and experimental procedures were approved by the Laboratory Animal Ethics Committee of Jinan University of China(approval No. 20111008001) in 2011. | Shi-Qin Lv Wutian Wu | 2021 | Neural Regeneration Research2021，16，8： | 2 |
| 7 | Contrasting neuropathology and functional recovery after spinal cord injury in developing and adult rats显示文摘Conflicting findings exist regarding the link between functional recovery and the regrowth of spinal tracts across the lesion leading to the restoration of functional contacts. In the present study, we investigated whether functional locomotor recovery was attributable to anatomical regeneration at postnatal day 1 (PN1), PN7, PN14 and in adult rats two months after transection injury at the tenth thoracic segment of the spinal cord. The Basso, Beattie, and Bresnahan scores showed that transection led to a failure of hindlimb locomotor function in PN14 and adult rats. However, PN1 and PN7 rats showed a significant level of stepping function after complete spinal cord transection. Unexpectedly, unlike the transected PN14 and adult rats in which the spinal cord underwent limited secondary degeneration and showed a scar at the lesion site, the rats transected at PN1 and PN7 showed massive secondary degeneration both anterograde and retrograde, leaving a >5-mm gap between the two stumps. Furthermore, retrograde tracing with fluorogold (FG) also showed that FG did not cross the transection site in PN1 and PN7 rats as in PN14 and adult rats, and re-transection of the cord caused no apparent loss in locomotor performance in the rats transected at PN1. Thus, these three lines of evidence strongly indicated that the functional recovery after transection in neonatal rats is independent of regrowth of spinal tracts across the lesion site. Our results support the notion that the recovery of locomotor function in developing rats may be due to intrinsic adaptations in the spinal circuitry below the lesion that control hindlimb locomotor activity rather than the regrowth of spinal tracts across the lesion. The difference in secondary degeneration between neonatal and adult rats remains to be explored. | Qiuju Yuan Huanxing Su Kin Chiu Wutian Wu Zhi-Xiu Lin | 2013 | Neuroscience Bulletin2013，29，4： | 2 |
| 8 | Parallelized volumetric fluorescence microscopy with a reconfigurable coded incoherent light-sheet array显示文摘Parallelized fluorescence imaging has been a long-standing pursuit that can address the unmet need for a comprehensive three-dimensional(3D)visualization of dynamical biological processes with minimal photodamage.However,the available approaches are limited to incomplete parallelization in only two dimensions or sparse sampling in three dimensions.We hereby develop a novel fluorescence imaging approach,called coded light-sheet array microscopy(CLAM),which allows complete parallelized 3D imaging without mechanical scanning.Harnessing the concept of an“infinity mirror”,CLAM generates a light-sheet array with controllable sheet density and degree of coherence.Thus,CLAM circumvents the common complications of multiple coherent light-sheet generation in terms of dedicated wavefront engineering and mechanical dithering/scanning.Moreover,the encoding of multiplexed optical sections in CLAM allows the synchronous capture of all sectioned images within the imaged volume.We demonstrate the utility of CLAM in different imaging scenarios,including a light-scattering medium,an optically cleared tissue,and microparticles in fluidic flow.CLAM can maximize the signal-to-noise ratio and the spatial duty cycle,and also provides a further reduction in photobleaching compared to the major scanning-based 3D imaging systems.The flexible implementation of CLAM regarding both hardware and software ensures compatibility with any light-sheet imaging modality and could thus be instrumental in a multitude of areas in biological research. | Yu-Xuan Ren Jianglai Wu Queenie T.K.Lai Hei Ming Lai Dickson M.D.Siu Wutian Wu Kenneth K.Y.Wong Kevin K.Tsia | 2020 | Light(Science & Applications)2020，9，1： | 2 |
| 9 | Immediate expression of Cdh2 is essential for efficient neural differentiation of mouse induced pluripotent stem cells显示文摘 | Huanxing Su Lihui Wang Wenhao Huang Dajiang Qin Jinglei Cai Xiaoli Yao Chengqian Feng Zhiyuan Li Yitao Wang Kwok-Fai So Guangjin Pan Wutian Wu Duanqing Pei | 2013 | Stem Cell Research2013，，： | 1 |
| 10 | Inhibition of nitric oxide synthase reduces motoneuron death due to spinal root avulsion显示文摘 | WUTIAN WU LINXI LI | 1993 | Neuroscience letters1993，153，22： | 1 |
| 11 | Spinal root avulsion:an excellent model for studying motoneuron degeneration and regeneration after severe axonal injury显示文摘Spinal root avulsion is an excellent model for studying the response of motoneurons to severe injury to their axons(Koliatsos et al.,1994).In this model(‘Avulsion Model’),spinal roots are torn off from spinal cord without removing the vertebra | Carolin Ruven Tak-Kwong Chan Wutian Wu | 2014 | Neural Regeneration Research2014，9，2： | 1 |
| 12 | The visual word form area: evidence from an fMRI study of implicit processing of Chinese characters显示文摘 | Liu Chao Zhang Wutian Tang Yiyuan | 2008 | Neuroimage2008，40，3： | 1 |
| 13 | Calcitonin gene-related peptide in anterior and posterior horns of spinal cord after brachial plexus injury显示文摘BACKGROUND:The changes of calcitonin gene-related peptide(CGRP)expression are closely associated with peripheral nerve injury,whereas it should be further investigated whether the damage of central nerve can lead to the changes of CGRP expression,and whether it is associated with the neural regeneration and repair.OBJECTIVE:To observe the changing law of CGRP expression in the anterior and posterior horns of spinal cord following brachial plexus injury.DESIGN:A randomized controlled trial.SETTINGS:Department of Anatomy,Yunyang Medical College;Department of Anatomy,Basic Medical College,Sun Yat-sen University.MATERIALS:Sixty-five adult male SD rats of clean degree,weighing 180-220 g,provided by the experimental animal center of the Basic Medical College,Sun Yat-sen University,were randomly divided into control group(n =5)and experimental group(n =60),and the latter was subdivided into three damage groups:avulsion of anterior root group(n =20),disjunction of posterior root group(n =20)and transection of spinal cord group(n =20).Diaminobenzidine(DAB)chromogen,rabbit anti-CGRP polyclonal antibody were the products of Sigma Company;Leica image analytical apparatus was produced by QUIN Company(Germany);Histotome by Sigma Company.METHODS:The experiments were carried out in the Department of Anatomy,Basic Medical College,Sun Yat-sen University from September 2004 to March 2005.Three kinds of models of brachial plexus injury were established:In the avulsion of anterior root group,right C7 anterior root was avulsed,and the distal nerve residual root was transected.In the disjunction of posterior root group,right C7 anterior root was avulsed and right C5-T1 posterior horns were cut to block the sensory afferent pathway.In the transection of spinal cord group,right C7 anterior root was avulsed and C5-6 segments of right spinal cord were semi-transected to block the cortical descending pathway.In the control group,C5-T1 vertebral plates were prayed open,and then the skin was sutured.The C7 segments of spinal cord were removed on the 1st,3rd,7th and 14th days postoperatively respectively,and the CGRP expressions in the anterior and posterior horns of spinal cord were determined and analyzed using immunohistochemical method and image analysis.MAIN OUTCOME MEASURES:① Number of CGRP immuno-positive motor neurons in the anterior horn of spinal cord;② Total area of CGRP immuno-positive fibers in the posterior horn of spinal cord.RESULTS:All the 65 rats were involved in the analysis of results.① Number of CGRP immuno-positive motor neurons in the anterior horn of spinal cord:CGRP immuno-positive motor neurons could be observed in the anterior horns of C7 spinal cord in the control group and damage groups,the neurons had big cell body with stained cytoplasm,appeared as brown granules,and mainly distributed in the ventral lateral anterior horn of spinal cord.On the 1st day postoperatively,the number of CGRP positive neurons was obviously higher in the in the avulsion of anterior root group than in the control group(P < 0.01),whereas obviously lower in the disjunction of posterior root group than in the control group(P < 0.01),and there was no obvious difference between the transection of spinal cord group and the control group(P > 0.05).On the 7th day,the numbers of CGRP positive neurons in the damage groups were obviously higher than that in the control group(P < 0.01),also obviously different from those on the 1st day in the same group respectively(P < 0.01).On the 14th day,the number of CGRP positive neurons in the disjunction of posterior root group was decreased,but there was no obvious difference as compared with that in the control group,whereas those in the avulsion of anterior root group and transection of spinal cord group were still obviously higher than that in the control group(P < 0.01).The number of CGRP positive neurons was the most in the avulsion of anterior root group,followed by the transection of spinal cord group,and the least in the disjunction of posterior root group,and there were significant differences among them(P < 0.01).② Total area of CGRPimmuno-positive fibers in the posterior horn of spinal cord:Dense CGRP immuno-positive nerve fibers distributed in the layers Ⅰ and Ⅱ of the C7 posterior horn of spinal cord in the control group.On the 1st day postoperatively,the total areas of CGRP positive fibers in the avulsion of anterior root group and transection of spinal cord group were obviously larger than that in the control group(P < 0.01),whereas there was no obvious difference between the disjunction of posterior root group and control group.On the 7th day,the CGRP expression in the posterior horn of spinal cord decreased to the lowest level in the disjunction of posterior root group,whereas there were no obvious differences in the avulsion of anterior root group and transection of spinal cord group as compared with that in the control group(P > 0.05).On the 14th day,the area continued to decrease in the avulsion of anterior root group and transection of spinal cord group,and it was obviously lower in the transection of spinal cord group than in the control group(P < 0.01),and it was slightly increased in the disjunction of posterior root group as compared with that on 7th day,but still obviously lower than that in the control group(P < 0.01).CONCLUSION:The expression and role of CGRP are in discrepancy in the anterior and posterior horns of spinal cord after brachial plexus injury.The CGRP in anterior horn of spinal cord are derived from the cell body of motor neurons,and may be involved in the repairing mechanism of nerve injury regeneration;Whereas those in the posterior horn are mainly derived from posterior root ganglion,and may be associated with the conduction of noxious stimulations. | Longju Chen Peijun Wang Feng Li Wutian Wu | 2007 | Neural Regeneration Research2007，2，4： | 1 |
| 14 | Implantation of adult bone marrow-derived mesenchymal stem cells transfected with the neurotrophin-3 gene and pretreated with retinoic acid in completely transected spinal cord显示文摘 | Wei Zhang Qing Yan Yuan-shan Zeng Xue-bao Zhang Yi Xiong Jun-mei Wang Shui-jun Chen Yan Li Iain C. Bruce Wutian Wu | 2010 | Brain Research2010，，： | 1 |
| 15 | Implantation of PNS graft inhibits the induction of neuronal nitric oxide synthase and enhances following root avulsion显示文摘 | Wutian Wu Kai Han Linxi Li | 1994 | Exp Neurol1994，129，33： | 1 |
| 16 | Expression of nitric--oxide synthase (NOS) in injured CNS neurons as shown by NADPH diaphorase histochemistry显示文摘 | Wutian Wu | 1993 | Exp Neurol1993，120，15： | 1 |
| 17 | Up-regulated Endogenous Erythropoietin/Erythropoietin Receptor System and Exogenous Erythropoietin Rescue Retinal Ganglion Cells after Chronic Ocular Hypertension显示文摘 | Qing-Ling Fu Wutian Wu Hua Wang Xin Li Vincent W. H. Lee Kwok-Fai So | 2008 | Cellular and Molecular Neurobiology2008，，2： | 1 |
| 18 | Self-assembling peptide nanofibrous hydrogel as a promising strategy in nerve repair after traumatic injury in the nervous system显示文摘Following injury in central nervous system(CNS),there are pathological changes in the injured region,which include neuronal death,axonal damage and demyelination,inflammatory response and activation of glial cells.The proliferation of a large number of astrocytes results in the formation of glial scar。 | Na Zhang Liumin He Wutian Wu | 2016 | Neural Regeneration Research2016，11，5： | 1 |
| 19 | Deactivations during the numerical processing显示文摘Deactivation has been encountered frequently in functional brain imaging researches. However, the deactivations during the numerical processing have not been reported yet. In this study, the functional magnetic resonance imaging (fMRI) was employed to investigate the pattern of the deactivation in the brain of 15 healthy subjects during the numerical addition task. Analyses revealed significant deactivations in several brain regions, including the posterior cingulate, precuneus, anterior cingulate and prefrontal cortex. Especially, we found notable deactivation in bilateral insula. Accounting for the cognitive functions of these regions participating in a combinated way, we discuss their contributions in sustaining the brain activity during conscious resting state, and indicate that the insula is an important area of gathering auditory information from the external world. | FENG HongBo ZHANG Ye TANG YiYuan JIN Jing DONG Feng FENG ShiGang ZHANG WuTian | 2007 | Chinese Science Bulletin2007，52，13： | 1 |
| 20 | Transplanted motoneurons derived from human induced pluripotent stem cells form functional connections with target muscle显示文摘 | Huanxing Su Lihui Wang Jinglei Cai Qiuju Yuan Xiaoying Yang Xiaoli Yao Wai-Man Wong Wenhao Huang Zhiyuan Li Jian-Bo Wan Yitao Wang Duanqing Pei Kwok-Fai So Dajiang Qin Wutian Wu | 2013 | Stem Cell Research2013，，1： | 1 |
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