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Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

Neural Regeneration Research 2025年第5期20卷 1364-1376页

作者： Ronglin Han Lanxin Luo Caiyan Wei Yaru Qiao Jiming Xie Xianchao Pan Juan Xing department of pathophysiology School of Basic Medical SciencesSouthwest Medical UniversityLuzhouSichuan ProvinceChina department of Medicinal Chemistry School of PharmacySouthwest Medical UniversityLuzhouSichuan ProvinceChina

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

关键词： alginate axon growth biomaterials extracellular matrix neural repair neurons neuroregeneration polyacrylamide polydimethylsiloxane stiffness

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New insights on the role of chondroitin sulfate proteoglycans in neural stem cell–mediated repair in spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1699-1700页

作者： Seyed Mojtaba Hosseini Soheila Karimi-Abdolrezaee department of Physiology and pathophysiology Spinal Cord Research CentreRady Faculty of Health SciencesUniversity of ManitobaWinnipegMBCanada Manitoba Multiple Sclerosis Research Center WinnipegMBCanada Children Hospital Research Institute of Manitoba WinnipegMBCanada

Extensive neurodegeneration is a hallmark of traumatic spinal cord injury (SCI) that underlies permanent sensorimotor and autonomic impairments (Alizadeh et al.,2019).Following the primary impact,the spinal cord undergoes a cascade of secondary injury mechanisms that are driven by disruption of the blood-spinal cord ba rrier,vascula r inju ry,glial reactivity,neu roinfla mmation,oxidative stress,lipid peroxidation,and glutamate excitotoxicity that culminate in neuronal and oligodendroglial cell death,demyelination,and axonal damage(Alizadeh et al.,2019).To achieve a meaningful functional recovery after SCI,regeneration of new neurons and oligodendrocytes and their successful growth and integration within the neural network are critical steps for reconstructing the damaged spinal cord tissue (Fischer et al.,2020).

关键词： peroxidation Fischer injury

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The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

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Neural Regeneration Research 2025年第2期20卷 402-415页

作者： Xiaorong Zhang Zhiying Chen Yinyi Xiong Qin Zhou Ling-Qiang Zhu Dan Liu department of Pathology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Jiujiang Clinical Precision Medicine Research Center JiujiangJiangxi ProvinceChina Center for Cognitive Science and Transdisciplinary Studies Jiujiang UniversityJiangxi ProvinceChina department of Neurology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina department of Rehabilitation Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina department of pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic ***,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia *** in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive *** oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous ***,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular *** review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular ***,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

关键词： endoplasmic reticulum stress endothelial nitric oxide synthase gene therapy nitric oxide NO-sGC-cGMP pathway synaptic dysfunction vascular dementia

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Repetitive traumatic brain injury–induced complement C1–related inflammation impairs long-term hippocampal neurogenesis

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Neural Regeneration Research 2025年第3期20卷 821-835页

作者： Jing Wang Bing Zhang Lanfang Li Xiaomei Tang Jinyu Zeng Yige Song Chao Xu Kai Zhao Guoqiang Liu Youming Lu Xinyan Li Kai Shu department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina department of Neurosurgery Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina department of pathophysiology School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Institute for Brain Research Wuhan Center of Brain ScienceHuazhong University of Science and TechnologyWuhanHubei ProvinceChina department of Graduate Student Chongqing Medical UniversityChongqingChina department of Basic Medicine School of Medical ScienceHubei University for NationalitiesEnshiHubei ProvinceChina department of Anatomy School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive ***,the mechanism underlying this neurogenesis impairment remains *** this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain *** results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and *** with repetitive traumatic brain injuryalso showed deficits in spatial memory ***,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was *** inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological *** findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

关键词： complement C1 dendrite dentate gyrus hippocampus neural stem cell neurogenesis neuroinflammation neurological function neuron traumatic brain injury

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Systematical identification of regulatory GPCRs by single-cell trajectory inference reveals the role of ADGRD1 and GPR39 in adipogenesis

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Science China Life Sciences 2025年

作者： Chuan Ye Xuemei Wang Jun Lin Chenyang Wu Yuhua Gao Chenghao Guo Yunxi Liao Ziyan Rao Shaodong Huang Weixuan Chen Ying Huang Jinpeng Sun Dongyu Zhao Changtao Jiang Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third Hospital department of Physiology and pathophysiology School of Basic Medical SciencesPeking University department of Biomedical Informatics School of Basic Medical SciencesPeking University State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Center for Obesity and Metabolic Disease Research School of Basic Medical SciencesPeking University State Key Laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and GynecologyPeking University Third Hospital National Clinical Research Center for Obstetrics and Gynecology Peking University Third Hospital department of Endocrinology and Metabolism Peking University Third Hospital Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong University department of Immunology School of Basic Medical SciencesPeking University

Adipogenesis is the healthy expansion of white adipose tissue (WAT),serving as a compensatory response to maintain metabolic homeostasis in the presence of excess energy in the ***,the identification of novel regulatory molecules in adipogenesis,specifically membrane receptors such as G protein-coupled receptors (GPCRs),holds significant clinical *** receptors can serve as viable targets for pharmaceuticals,offering potential for restoring metabolic homeostasis in individuals with *** utilized trajectory inference methods to analyze three distinct single-nucleus sequencing (sNuc-seq) datasets of adipose tissue and systematically identified GPCRs with the potential to regulate *** verification in primary adipose progenitor cells (APCs) of mice,we discovered that ADGRD1 promoted the differentiation of APCs,while GPR39 inhibits this *** the obese mouse model induced by a high-fat diet(HFD),both gain-of-function and loss-of-function studies validated that ADGRD1 promoted adipogenesis,thereby improving metabolic homeostasis,while GPR39 inhibited adipogenesis,leading to metabolic ***,through the analysis of 2,400 ChIP-seq data and 1,204 bulk RNA-seq data,we found that the transcription factors (TFs) MEF2D and TCF12 regulated the expression of ADGRD1and GPR39,*** study revealed the regulatory role of GPCRs in adipogenesis,providing novel targets for clinical intervention of metabolic dysfunction in obese patients.

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Inhibition of Expression of Hypoxia-inducible Factor-1α mRNA by Nitric Oxide in Hypoxic Pulmonary Hypertension Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2004年第1期24卷 5-8页

作者：敖启林黄磊朱朋成熊密王迪浔 department of Pathology and pathophysiology department of Obstetrics and Gynecology

In order to study the effect of nitric oxide (NO) on the expression of hypoxia inducible factor 1 alpha (HIF 1α) mRNA in hypoxic pulmonary hypertension (HPH) rats, 30 healthy male Wistar rats were randomly divided into normoxic control group, chronic hypoxic group and hypoxia plus L argine (L Arg) group. The animal model of HPH was developed. The mean pulmonary arterial pressure (mPAP) was measured by inserting a microcatheter into the pulmonary artery. The HIF 1α mRNA expression levels were detected by in situ hybridization (ISH) and semiquantitative RT PCR. It was found that after 14 days hypoxia, the mPAP in normoxic control group (17.6±2 7 mmHg,1 mmHg=0 133 kPa) was significantly lower than that in chronic hypoxic group(35.8±6.1 mmHg, t =0.2918, P <0.05) and mPAP in chronic hypoxic group was higher than that in hypoxia plus L argine group(24.4±3.8 mmHg, t =0.2563, P <0.05). ISH showed that the expression of HIF 1α mRNA in the intraacinar pulmonary arteriolae (IAPA) in normoxic control group (0.1076±0.0205) was markedly weaker than that in chronic hypoxic group (0.3317±0.0683, t =3.125, P <0.05) and that in chronic hypoxic group was stronger than that in hypoxia plus L argine group (0.1928±0.0381, t =2.844, P <0.05). RT PCR showed that the content of HIF 1α mRNA in chronic hypoxic group (2.5395±0.6449) was 2.16 times and 1.75 times higher than that in normoxic control group (1.1781±0.3628) and hypoxia plus L argine group (1.4511±0.3981), respectively. It is concluded that NO can reduce the mPAP by the inhibition of the expression of HIF 1α mRNA, which may be one of the mechanisms through which NO affects the pathogenesis of HPH.

关键词： nitric oxide hypoxia-inducible factor-1 alpha hypoxic pulmonary hypertension

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Inflammatory bowel disease:Pathogenesis

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World Journal of Gastroenterology 2014年第1期20卷 91-99页

作者： Yi-Zhen Zhang Yong-Yu Li department of pathophysiology Tongji University School of Medicine

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. It has been a worldwide health-care problem with a continually increasing incidence. It is thought that IBD results from an aberrant and continuing immune response to the microbes in the gut, catalyzed by the genetic susceptibility of the individual. Although the etiology of IBD remains largely unknown, it involves a complex interaction between the genetic, environmental or microbial factors and the immune responses. Of the four components of IBD pathogenesis, most rapid progress has been made in the genetic study of gut inflammation. The latest internationally collaborative studies have ascertained 163 susceptibility gene loci for IBD. The genes implicated in childhood-onset and adult-onset IBD overlap, suggesting similar genetic predispositions. However, the fact that genetic factors account for only a portion of overall disease variance indicates that microbial and environmental factors may interact with genetic elements in the pathogenesis of IBD. Meanwhile, the adaptive immune response has been classically considered to play a major role in the pathogenesis of IBD, as new studies in immunology and genetics have clarified that the innate immune response maintains the same importance in inducing gut inflammation. Recent progress in understanding IBD pathogenesis sheds lights on relevant disease mechanisms, including the innate and adaptive immunity, and the interactions between genetic factors and microbial and environmental cues. In this review, we provide an update on the major advances that have occurred in above areas. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

关键词： Inflammatory bowel disease Ulcerative colitis Crohn's disease pathogenesis Genetics Microbial factors Immune responses

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ELECTROPHYSIOLOGICAL STUDIES ON THE TERMINATION SITES OF DOUBLE PROJECTION SPINAL DORSAL HORN NEURONS IN THE CAT

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Science in China,Ser.B 1986年第6期29卷 634-643页

作者：吕国蔚张肃夏予 department of neurophysiology Beijing Second Medical College

Some projection neurons in laminae Ⅲ, Ⅳ and Ⅴ of the felline lumbar dorsal horn have been found to be antidromically driven from stimulation of both the ipsilateral cervical dorsal and dorsolateral funiculi that are well-dissected and insulated from one another. No detectable responses can be evoked from these nenrons when stimulation is applied to sites rostral to the lateral cervical nucleus and the dorsal column nuclei, suggesting that the dorsal and dorsolateral funicular branches of these neuron’s axons terrninate in the lateral cervical nucleus and the dorsal column nuclei, respectively. The results indicate that these neurons axe an intersection set of the spinal cervical tract (SCT) and dorsal column postsynaptic (DCPS) neurons and have been thus named spinal cervical tract-dorsal column postsynaptie (SCT-DCPS) neurons.

关键词： DLF SCT ELECTROPHYSIOLOGICAL STUDIES ON THE TERMINATION SITES OF DOUBLE PROJECTION SPINAL DORSAL HORN NEURONS IN THE CAT

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Perspectives for the association between olfactory disturbances and depression in Parkinson's disease

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Neural Regeneration Research 2019年第4期14卷 591-592页

作者： Jessica L.Ilkiw Marcelo M.S.Lima neurophysiology Laboratory Department of PhysiologyFederal University of Paraná

Non-motor disturbances in Parkinson’s disease:Globally,population aged 60 or over is growing and considering the World Bank predictions for the next 20 years it is expected that the number of Parkinson’s disease(PD)cases will double at the end of this period thus,reaching an impressive 13–39 million patients *** scenario is potentially associated with a significant global negative impact on public health systems particularly in countries with increased ageing populations such as the European countries,Asia and *** pathophysiology of PD involves the progressive degeneration of dopaminergic neurons of the substantia nigra pars compacta(SNpc)that triggers denervation of the nigrostriatal pathway and consequent significant reduction of dopamine in the dorsal *** process leads to a critical motor impairment scenario characterized by bradykinesia,rigidity,resting tremor,and postural instability(Emamzadeh and Surguchov,2018).However,several other non-motor disturbances develop earlier,thus,being considered as prodromal signs of the *** this sense,the literature is increasingly emphasizing the importance of investigating mood and olfactory disruptions as high sensitive benchmarks of the early-phase *** fact,the need for innovative early-phase diagnostic tools,as well as the elucidation of the pathophysiological mechanisms of such disturbances,is essential priority in the field of investigation of ***,in the year of 2015,a woman was known for an intriguing ability of“smell PD”.Her husband had lived with the disease for twenty years and during this process she noticed that his odor slowly changed to a musky ***,this woman could associate this particular smell with PD after meeting different people with this distinct odor in a charity for PD *** fact,this clever observation is aligned with studies showing that hyposmia is found decades before the motor *** type of anecdotal story,

关键词： Parkinson olfactory disturbances association

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Melatonin attenuatesβ-amyloid-induced inhibition of neurofilament expression

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Acta Pharmacologica Sinica 2004年第4期25卷 49-53页

作者： Ying-chun ZHANG, Ze-fen WANG, Qun WANG, Yi-pengWANG, Jian-zhi WANG2 department of pathophysiology, Tongji Medical College, Huazhong University ofScience and Technology, Wuhan 430030, China department of pathophysiology Tongji Medical College Huazhong University of Science and Technology

AIM: To explore the effect of β-amyloid (Aβ) on metabolism of cytoskeletal protein neurofilament, and search for effective cure to the lesion. METHODS: Wild type murine neuroblastoma N2a (N2awt) and N2a stably transfected with wild type amyloid precursor protein (N2aAPP) were cultured. Sandwich ELISA, immunocytochemistry, and Western blot were used respectively to measure the level of Aβ, the expression and phosphorylation of neurofilament proteins. RESULTS: The immunoreactivity of neurofilament protein was almost abolished in N2aAPP, which beard a significantly higher level of Aβ. Melatonin effectively decreased the level of Aβ, and restored partially the level of phosphorylated and non-phosphorylated neurofilament in N2aAPP. CONCLUSION: Overproduction of Aβ inhibits neurofilament expression, and melatonin attenuates the Aβ-induced lesion in cytoskeletal protein.

关键词： Alzheimer disease amyloid beta-protein neurofilament proteins melatonin

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