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Collagen/heparan sulfate porous scaffolds loaded with neural stem cells improve neurological function in a rat model of traumatic brain injury

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Neural Regeneration Research 2021年第6期16卷 1068-1077页

作者： Jian Zhang Ren-Jie Wang Miao chen Xiao-yin Liu Ke Ma Hui-You xu Wu-Sheng Deng yi-Chao Ye Wei-Xin Li xu-yi chen Hong-Tao Sun Tianjin Key Laboratory of Neurotrauma Repair Institute of Traumatic Brain Injury and NeuroscienceCharacteristic Medical Center of Chinese People’s Armed Police ForceTianjinChina Graduate School Logistics University of People’s Armed Police ForceTianjinChina Graduate School Affiliated Hospital of Traditional Chinese MedicineXinjiang Medical UniversityUrumqiXinjiang Uygur Autonomous RegionChina Graduate School Tianjin Medical UniversityTianjinChina

One reason for the poor therapeutic effects of stem cell transplantation in traumatic brain injury is that exogenous neural stem cells cannot effectively migrate to the local injury site,resulting in poor adhesion and proliferation of neural stem cells at the injured *** enhance the targeted delivery of exogenous stem cells to the injury site,cell therapy combined with neural tissue engineering technology is expected to become a new strategy for treating traumatic brain ***/heparan sulfate porous scaffolds,prepared using a freeze-drying method,have stable physical and chemical *** scaffolds also have good cell biocompatibility because of their high porosity,which is suitable for the proliferation and migration of neural stem *** the present study,collagen/heparan sulfate porous scaffolds loaded with neural stem cells were used to treat a rat model of traumatic brain injury,which was established using the controlled cortical impact *** 2 months after the implantation of collagen/heparan sulfate porous scaffolds loaded with neural stem cells,there was significantly improved regeneration of neurons,nerve fibers,synapses,and myelin sheaths in the injured brain ***,brain edema and cell apoptosis were significantly reduced,and rat motor and cognitive functions were markedly *** findings suggest that the novel collagen/heparan sulfate porous scaffold loaded with neural stem cells can improve neurological function in a rat model of traumatic brain *** study was approved by the Institutional Ethics Committee of Characteristic Medical Center of Chinese People’s Armed Police Force,China(approval No.2017-0007.2)on February 10,2019.

关键词： collagen heparan sulfate injury neural stem cells regeneration repair scaffold traumatic brain injury morris water maze motor evoked potential synapses myelin sheaths

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Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury

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Neural Regeneration Research 2016年第6期11卷 931-936页

作者： Yue Tu Xiao-mei Miao Tai-long yi xu-yi chen Hong-tao Sun Shi-xiang cheng Sai Zhang Tianjin Key Laboratory of Neurotrauma Repair Institute of Traumatic Brain Injury & Neuroscience of Chinese People's Armed Police ForcesNeurosurgery & Neurology Hospital Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces Graduate School Tianjin University of Traditional Chinese Medicine

Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and bloodbrain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points（20 μL, twice a day, for 2 days） and mild induced hypothermia（6 hours） are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury.

关键词： traumatic alone edema neurological minutes hematoma hematoxylin olfactory neuronal twice

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Co-culture of oligodendrocytes and neurons can be used to assess drugs for axon regeneration in the central nervous system

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Neural Regeneration Research 2015年第10期10卷 1612-1616页

作者： Lin Gang Yu-chen Yao ying-fu Liu yi-peng Li Kai Yang Lei Lu Yuan-chi cheng xu-yi chen Yue Tu Neurological Hospital of Affiliated Hospital of Logistics University of Chinese People’s Armed Police Force Tianjin University of Traditional Chinese Medicine Logistics University of Chinese People’s Armed Police Forces Liaoning Medical University Key Laboratory of Nerve Trauma Repair

We present a novel in vitro model in which to investigate the efficacy of experimental drugs for the promotion of axon regeneration in the central nervous system. We co-cultured rat hippocampal neurons and cerebral cortical oligodendrocytes, and tested the co-culture system using a Nogo-66 receptor antagonist peptide（NEP1–40）, which promotes axonal growth. Primary cultured oligodendrocytes suppressed axonal growth in the rat hippocampus, but NEP1–40 stimulated axonal growth in the co-culture system. Our results confirm the validity of the neuron-oligodendrocyte co-culture system as an assay for the evaluation of drugs for axon regeneration in the central nervous system.

关键词： nerve regeneration experimental models NEP1–40 oligodendrocytes neurons axon regeneration Nogo PC12 cells neural regeneration

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Neurological functional evaluation based on accurate motions in big animals with traumatic brain injury

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Neural Regeneration Research 2019年第6期14卷 991-996页

作者： Ji-Peng Jiang xue-Gang Niu chen Dai Ke Ma Hui-You xu Shi-Xiang cheng Zhi-Wen Zhang Feng Duan xu Zhu Yu-Ting Wang xu-yi chen Sai Zhang Center for Neurology and Neurosurgery Medical Center of People's Armed Policed ForceKey Laboratory of Neurotrauma Repair of Tianjin Department of Neurosurgery Tianjin Fourth Central Hospital Department of Automation College of Computer and Control EngineeringNankai University Graduate School Tianjin Medical University

An accurate and effective neurological evaluation is indispensable in the treatment and rehabilitation of traumatic brain injury. However,most of the existing evaluation methods in basic research and clinical practice are not objective or intuitive for assessing the neurological function of big animals, and are also difficult to use to qualify the extent of damage and recovery. In the present study, we established a big animal model of traumatic brain injury by impacting the cortical motor region of beagles. At 2 weeks after successful modeling, we detected neurological deficiencies in the animal model using a series of techniques, including three-dimensional motion capture, electromyogram and ground reaction force. These novel technologies may play an increasingly important role in the field of traumatic brain injury diagnosis and rehabilitation in the future. The experimental protocol was approved by the Animal Care and Use Committee of Logistics University of People's Armed Police Force(approval No. 2017-0006.2).

关键词： nerve regeneration evaluation method neurological deficiency traumatic brain injury motion capture electromyogram ground reaction force neural regeneration

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Polyethylene glycol as a promising synthetic material for repair of spinal cord injury

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Neural Regeneration Research 2017年第6期12卷 1003-1008页

作者： Xian-bin Kong Qiu-yan Tang xu-yi chen Yue Tu Shi-zhong Sun Zhong-lei Sun Department of Brain Affiliated Hospital of China Logistics College of People's Armed Police Forces Tianjin University of Traditional Chinese Medicine Tianjin Key Laboratory of Neurological Trauma Repair Jinzhou Medical University

Polyethylene glycol is a synthetic, biodegradable, and water-soluble polyether. Owing to its good biological and material properties, polyethylene glycol shows promise in spinal cord tissue engineering applications. Although studies have examined repairing spinal cord injury with polyethylene glycol, these compelling findings have not been recently reviewed or evaluated as a whole. Thus, we herein review and summarize the findings of studies conducted both within and beyond China that have examined the repair of spinal cord injury using polyethylene glycol. The following summarizes the results of studies using polyethylene glycol alone as well as coupled with polymers or hydrogels：（1） polyethylene glycol as an adjustable biomolecule carrier resists nerve fiber degeneration, reduces the inflammatory response, inhibits vacuole and scar formation, and protects nerve membranes in the acute stage of spinal cord injury.（2） Polyethylene glycol-coupled polymers not only promote angiogenesis but also carry drugs or bioactive molecules to the injury site. Because such polymers cross both the blood-spinal cord and blood-brain barriers, they have been widely used as drug carriers.（3） Polyethylene glycol hydrogels have been used as supporting substrates for the growth of stem cells after injury, inducing cell migration, proliferation, and differentiation. Simultaneously, polyethylene glycol hydrogels isolate or reduce local glial scar invasion, promote and guide axonal regeneration, cross the transplanted area, and re-establish synaptic connections with target tissue, thereby promoting spinal cord repair. On the basis of the reviewed studies, we conclude that polyethylene glycol is a promising synthetic material for use in the repair of spinal cord injury.

关键词： glycol repair polyethylene degeneration hydrogel scaffold synaptic alone biodegradable inducing

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Three-dimensional bioprinting collagen/silk fibroin scaffold combined with neural stem cells promotes nerve regeneration after spinal cord injury

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Neural Regeneration Research 2020年第5期15卷 959-968页

作者： Ji-Peng Jiang Xiao-yin Liu Fei Zhao Xiang Zhu Xiao-yin Li xue-Gang Niu Zi-Tong Yao chen Dai Hui-You xu Ke Ma xu-yi chen Sai Zhang Department of Thoracic Surgery General Hospital of People’s Liberation Army (PLA)BeijingChina Tianjin Key Laboratory of Neurotrauma Repair Institute of Traumatic Brain Injury and NeuroscienceCenter for Neurology and Neurosurgery of Chinese People’s Armed Police Force (PAP) Medical CenterTianjinChina Tianjin Medical University TianjinChina Department of Neurology Luoyang First Hospital of Traditional Chinese MedicineLuoyangHenan ProvinceChina Department of Neurosurgery Fourth Central Hospital of TianjinTianjinChina

Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal ***,cell transplantation and bio-scaffold implantation are considered to be effective methods for neural *** study was designed to fabricate a type of three-dimensional collagen/silk fibroin scaffold (3D-CF) with cavities that simulate the anatomy of normal spinal *** scaffold allows cell growth in vitro and in *** observe the effects of combined transplantation of neural stem cells (NSCs) and 3D-CF on the repair of spinal cord *** Sprague-Dawley rats were divided into four groups: sham (only laminectomy was performed),spinal cord injury (transection injury of T10 spinal cord without any transplantation),3D-CF (3D scaffold was transplanted into the local injured cavity),and 3D-CF + NSCs (3D scaffold co-cultured with NSCs was transplanted into the local injured ***,imaging,hematoxylin-eosin staining,argentaffin staining,immunofluorescence staining,and western blot assay were *** from the sham group,neurological scores were significantly higher in the 3D-CF + NSCs group compared with other ***,latency of the 3D-CF + NSCs group was significantly reduced,while the amplitude was significantly increased in motor evoked potential *** results of magnetic resonance imaging and diffusion tensor imaging showed that both spinal cord continuity and the filling of injury cavity were the best in the 3D-CF + NSCs ***,regenerative axons were abundant and glial scarring was reduced in the 3D-CF + NSCs group compared with other *** results confirm that implantation of 3D-CF combined with NSCs can promote the repair of injured spinal *** study was approved by the Institutional Animal Care and Use Committee of People’s Armed Police Force Medical Center in 2017 (approval No.2017-0007.2).

关键词： 3D bioprinting collagen diffusion tensor imaging functional recovery magnetic resonance imaging nerve regeneration neural regeneration neural stem cell scaffold silk fibroin spinal cord injury

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Injectable collagen scaffold with human umbilical cordderived mesenchymal stem cells promotes functional recovery in patients with spontaneous intracerebral hemorrhage:phase Ⅰ clinical trial

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Neural Regeneration Research 2023年第9期18卷 1999-2004页

作者： Xiao-yin Li Wu-Sheng Deng Zi-Qi Wang Zheng-Chao Li Shu-Lian chen Zhen Song Quan Zhang Jin Liang xu-yi chen Characteristic Medical Center of Chinese People’s Armed Police Force Tianjin Key Laboratory of Neurotrauma RepairTianjinChina Department of Neurosurgery Dazhou Second People’s HospitalDazhouSichuan ProvinceChina Graduate School of Tianjin University of Traditional Chinese Medicine TianjinChina

Animal expe riments have shown that injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can promote recovery from spinal cord *** investigate whether injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can be used to treat spontaneous intracerebral hemorrhage,this non-randomized phase I clinical trial recruited patients who met the inclusion criteria and did not meet the exclusion crite ria of spontaneous intracerebral hemorrhage treated in the Characteristic Medical Center of Chinese People’s Armed Police Force from May 2016 to December *** were divided into three groups according to the clinical situation and patient benefit:control(n=18),human umbilical cord-derived mesenchymal stem cells(n=4),and combination(n=8).The control group did not receive any *** human umbilical cord-derived mesenchymal stem cells group received human umbilical cord-derived mesenchymal stem cell *** combination group received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem *** who received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells had more remarkable improvements in activities of daily living and cognitive function and smaller foci of intra cerebral hemorrhage-related *** adve rse events associated with cell transplantation were not *** collagen scaffold with human umbilical cord-derived mesenchymal stem cells appears to have great potential treating spontaneous intracerebral hemorrhage.

关键词： clinical trial collagen scaffold efficacy human umbilical cord-derived mesenchymal stem cells human safe neurological recovery spontaneous intracerebral hemorrhage transplantation

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Collagen scaffold combined with human umbilical cord-mesenchymal stem cells transplantation for acute complete spinal cord injury

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Neural Regeneration Research 2020年第9期15卷 1686-1700页

作者： Wu-Sheng Deng Ke Ma Bing Liang Xiao-yin Liu Hui-You xu Jian Zhang Heng-Yuan Shi Hong-Tao Sun xu-yi chen Sai Zhang College of Integrated Traditional Chinese and Western Medicine Gansu University of Chinese MedicineLanzhouGansu ProvinceChina Tianjin Key Laboratory of Neurotrauma Repair Pingjin Hospital Brain Centercharacteristic medical center of Chinese people’s armed police forceTianjinChina Clinical School of Medicine Tianjin Medical UniversityTianjinChina Clinical School of Medicine Logistics University of People’s Armed Police ForceTianjinChina

Currently, there is no effective strategy to promote functional recovery after a spinal cord injury. Collagen scaffolds can not only provide support and guidance for axonal regeneration, but can also serve as a bridge for nerve regeneration at the injury site. They can additionally be used as carriers to retain mesenchymal stem cells at the injury site to enhance their effectiveness. Hence, we hypothesized that transplanting human umbilical cord-mesenchymal stem cells on collagen scaffolds would enhance healing following acute complete spinal cord injury. Here, we test this hypothesis through animal studies and a phase I clinical trial.(1) Animal experiments: Models of completely transected spinal cord injury were established in rats and canines by microsurgery. Mesenchymal stem cells derived from neonatal umbilical cord tissue were adsorbed onto collagen scaffolds and surgically implanted at the injury site in rats and canines;the animals were observed after 1 week–6 months. The transplantation resulted in increased motor scores, enhanced amplitude and shortened latency of the motor evoked potential, and reduced injury area as measured by magnetic resonance imaging.(2) Phase I clinical trial: Forty patients with acute complete cervical injuries were enrolled at the Characteristic Medical Center of Chinese People's Armed Police Force and divided into two groups. The treatment group(n = 20) received collagen scaffolds loaded with mesenchymal stem cells derived from neonatal umbilical cordtissues;the control group(n = 20) did not receive the stem-cell loaded collagen implant. All patients were followed for 12 months. In the treatment group, the American Spinal Injury Association scores and activities of daily life scores were increased, bowel and urinary functions were recovered, and residual urine volume was reduced compared with the pre-treatment baseline. Furthermore, magnetic resonance imaging showed that new nerve fiber connections were formed, and diffusion tens

关键词： canine collagen scaffolds human human umbilical cord-mesenchymal stem cells nerve regeneration rat spinal cord injury

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Magnetic resonance imaging-three-dimensional printing technology fabricates customized scaffolds for brain tissue engineering

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Neural Regeneration Research 2017年第4期12卷 614-622页

作者： Feng Fu Zhe Qin Chao xu xu-yi chen Rui-xin Li Li-na Wang Ding-wei Peng Hong-tao Sun Yue Tu Chong chen Sai Zhang Ming-liang Zhao Xiao-hong Li Institute of Traumatic Brain Injury and Neurology Pingjin Hospital Logistics University of Chinese People's Armed Police Forces Tianjin China Key Laboratory of Neurotrauma Repair ofTianjin Tianjin China Pingjin Hospital Logistics University of Chinese People's Armed Police Forces Tianjin China Institute of Medical Equipment The Academy of Military Medical Sciences Tianjin China

Conventional fabrication methods lack the ability to control both macro- and micro-structures of generated scaffolds. Three-dimensional printing is a solid free-form fabrication method that provides novel ways to create customized scaffolds with high precision and accuracy. In this study, an electrically controlled cortical impactor was used to induce randomized brain tissue defects. The overall shape of scaffolds was designed using rat-specific anatomical data obtained from magnetic resonance imaging, and the internal structure was created by computer- aided design. As the result of limitations arising from insufficient resolution of the manufacturing process, we magnified the size of the cavity model prototype five-fold to successfully fabricate customized collagen-chitosan scaffolds using three-dimensional printing. Results demonstrated that scaffolds have three-dimensional porous structures, high porosity, highly specific surface areas, pore connectivity and good internal characteristics. Neural stem cells co-cultured with scaffolds showed good viability, indicating good biocompatibility and biodegradability. This technique may be a promising new strategy for regenerating complex damaged brain tissues, and helps pave the way toward personalized medicine.

关键词： nerve regeneration three-dimensional printing traumatic brain injury tissue engineering scaffolds magnetic resonance imaging collagen chitosan mimics neural regeneration

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SNR WALL AND COOPERATIVE SPECTRUM SENSING IN COGNITIVE RADIO UNDER NOISE UNCERTAINTY

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Journal of Electronics(China) 2010年第5期27卷 611-617页

作者： Wang Haijun Su Xin xu yi chen Xiang Wang Jing Tsinghua National Laboratory for Information Science and Technology Tsinghua University Beijing 100084China

Cooperative energy spectrum sensing has been proved effective to detect the spectrum holes in Cognitive Radio(CR).However,its performance may suffer from the noise uncertainty,which is portrayed by the SNR wall in some *** this paper we analyze the spectrum sensing per-formance under noise uncertainty and find an alternative approach to obtain the SNR *** the average SNR wall is proposed to illustrate the statistically average impact of noise *** addition,the cooperative sensing performance under noise uncertainty with AND rule is *** and numerical results show that cooperative sensing can significantly improve the sensing performance under the condition of noise uncertainty.

关键词： Cooperative spectrum sensing Noise uncertainty SNR wall

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