EBioMedicine
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2022
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IF 11.205
Xiaoqi Hong,Yujin Jian,Shenghao Ding,Jianpo Zhou,Xiaoli Zheng,Huimin Zhang,Butian Zhou,Canbin Zhuang,Jieqing Wan,Xiaoping Tong
Summary Background Stroke is one of the most common neurological diseases in the world and is clinically manifested by transient or permanent brain dysfunction. It has a high mortality and disability rate, which severely affects people's health and diminishes the quality of life. However, there is no efficient treatment that can be considered curative and there are other less well-known theories of pathogenesis. Therefore, it is imperative to gain a full understanding of the pathophysiology of ischemia and to seek new therapeutic strategies. Methods We first examined Kir4.1 channel and myelin based protein (MBP) expression in brain tissues from acute ischemic patients by Western blotting. We then established a transient ischemic mouse model (tMCAO) to conduct molecular, cell biological, transmission electron microscopy and pharmacokinetic studies, as well as in Kir4.1 cKO mice. Finally, neuroimaging and behavioral analyses were used to examine whether activation of Kir4.1 channel by luteolin could contribute to neuronal functional recovery in ischemic stroke. Findings In acute ischemic stroke patients, we first demonstrated that Kir4.1 ion channels were greatly impaired and a severe demyelination of axons occurred in ischemic infarction area of cerebral cortex in these patients. Further evidence showed that the deficits of Kir4.1 channels in NG2 glia led to the myelin loss of axons in a transient ischemic mouse model (tMCAO). Treating ischemic mice with a natural botanical extract, luteolin augmented Kir4.1 channel currents in NG2 glia and consequently promoted remyelination of axons, alleviated the infarction area and ultimately improved motor function in a series of behavioral tests. Interpretation Targeting Kir4.1 ion channels expressed in NG2 glial cells by luteolin treatment highlights an effective therapeutic strategy for a prompt brain functional recovery in ischemic stroke. Funding This work was supported by grants from the Ministry of Science and Technology China Brain Initiative (2022ZD0204702, to X.T.), the National Natural Science Foundation of China ( 82271466 , 82171279 , 31970904 and 31571063 ), the Program for Professor of Special Appointment (Eastern Scholar for Dr. X.T.) at Shanghai Institutions for Higher Learning ( 1510000084 ), Shanghai Pujiang Talent Award ( 15PJ1404600 ), Shanghai Municipal Science and Technology Major Project ( 2018SHZDZX05 ) and Shanghai Science and Technology Project ( 17411954000 ).
研究领域:
神经科学
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药理学
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分子生物学
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临床医学
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DOI
PubMed
高影响因子
Theranostics
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2020
·
IF 8.579
Teng Ma,Yafeng Yang,Xin Quan,Lei Lu,Bing Xia,Jianbo Gao,Fengyu Qi,Shengyou Li,Laihe Zhao,Liangwei Mei,Yi Zheng,Yanbing Shen,Zhuojing Luo,Yan Jin,Jinghui Huang
Rationale: Local hypoxia is a challenge for fabrication of cellular grafts and treatment of peripheral nerve injury. In our previous studies, we demonstrated that perfluorotributylamine (PFTBA) could provide short term oxygen supply to Schwann cells (SCs) and counteract the detrimental effects of hypoxia on SCs during the early stages of nerve injury. However, the quick release of oxygen in PFTBA compromised its ability to counteract hypoxia over an extended time, limiting its performance in peripheral nerve injury. Methods: In this study, PFTBA-based oxygen carrier systems were prepared through coaxial electrospinning to prolong the time course of oxygen release. Core-shell structures were fabricated, optimized, and the oxygen kinetics of PFTBA-enriched core-shell fibers evaluated. The effect of core-shells on the survival and function of SCs was examined in both 2D and 3D systems as well as in vivo . The system was used to bridge large sciatic nerve defects in rats. Results: PFTBA core-shell fibers provided high levels of oxygen to SCs in vitro , enhancing their survival, and increasing NGF, BDNF, and VEGF expression in 2D and 3D culture systems under hypoxic condition. In vivo analysis showed that the majority of GFP-expressing SCs in the PFTBA conduit remained viable 14 days post-implantation. We found that axons in PFTBA oxygen carrier scaffold improved axonal regeneration, remyelination, and recovery. Conclusion: A synthetic oxygen carrier in core-shell fibers was fabricated by the coaxial electrospinning technique and was capable of enhancing SC survival and nerve regeneration by prolonged oxygen supply. These findings provide a new strategy for fabricating cellular scaffolds to achieve regeneration in peripheral nerve injury treatment and other aerobic tissue injuries.
研究领域:
组织工程
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神经科学
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生物材料
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再生医学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
·
IF 13.2
Zuoxiang Dong,Jihu Zhao,Wenshuai Deng,Congxiao Wang,Zhiguo Chen,Peng Sun
Spinal cord injury (SCI) often leads to severe and long-lasting disability, profoundly impacting both the physical and mental well-being of patients. While rehabilitation and regenerative medicine represent promising avenues for SCI recovery, their combined application remains underexplored. In this study, we developed a biodegradable, low-swelling, multi-ionic hydrogel composed of oxidized dextran (ODex), dopamine-grafted gelatin (DG), and a combination of essential ions (Ca 2+ , Mg 2+ , Zn 2+ , and Fe 3+ ). This hydrogel exhibits a suite of desirable properties, including optimal pore size, excellent biocompatibility, injectability, minimal swelling, strong adhesiveness, and notable antioxidative capacity. Functionally, the hydrogel can block calcium channels, reduce neuronal excitability, and alleviate muscle stiffness. At the cellular level, it supports neuronal growth and enhances antioxidative defense mechanisms. Behavioral assessments and electrophysiological studies in animals demonstrated that the multi-ionic hydrogel promotes the generation of new neurons, axonal regeneration, synaptogenesis of various neurotransmitters, and supports remyelination. The results showed significant functional recovery in rodents, particularly in motor and sensory functions, with remarkable improvement in urinary retention. This study suggests that multi-ionic hydrogels hold great potential as a strategy for spinal cord injury repair and neural regeneration, and may also provide hope for tissue regeneration in other medical conditions.
研究领域:
生物材料
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神经科学
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组织工程
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再生医学
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生物医学工程
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产品关联
DOI
高影响因子
Molecular Medicine Reports
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2017
·Vol. 16
·期 2
·1864-1870
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IF 1.692
Chao Weng,Man Ding,Shanghua Fan,Qian Cao,Zuneng Lu
Transcription factor 7 like 2 (TCF7L2, also termed TCF4), is a Wnt effector induced transiently in the oligodendroglial lineage. The current well accepted hypothesis is that TCF7L2 inhibits oligodendrocyte differentiation and remyelination through canonical Wnt/β‑catenin signaling. However, recent studies indicated that TCF7L2 activity is required during oligodendrocyte differentiation and remyelination. In order to clarify this, in situ hybridization, immunofluorescence and western blot analysis using in vivo TCF7L2 conditional knockout mice, were performed and it was found that TCF7L2 promotes oligodendrocyte differentiation during myelin formation and remyelination. Furthermore, it was established that TCF7L2 does not affect oligodendrocyte precursor cells during remyelination. These data are of important clinical significance to develop novel therapeutic targets to overcome multiple sclerosis and other demyelinating diseases.
研究领域:
神经科学
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分子生物学
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细胞生物学
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神经病学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Junkai Zeng,Changjiang Gu,Yu Zhuang,Kaili Lin,Youzhuan Xie,Xiongsheng Chen
Spinal cord injury (SCI) is a devastating condition that results in sensory and motor dysfunctions below the injury site. Currently, there is no effective treatment. Extracellular vesicles (NEVs) derived from neural stem cells (NSCs) have shown promising potential in exerting neuroprotective effect. However, the limited yield and quality of NEVs restrict their further application. Melatonin, an indolamine hormone that is released from the pineal gland, was used in the present study to enhance the secretion and therapeutic effects of NEVs. Compared with original NEVs, NEVs derived from melatonin-pretreated NSCs (MNEVs) exhibited improved neuroregenerative and anti-inflammatory properties in vitro . Furthermore, to achieve prolonged retention in vivo, MNEVs were encapsulated in GelMA hydrogel microspheres ( [email protected] ). After encapsulation, MNEVs effectively accumulated at the site of injury over a 28-day period. The injection of [email protected] successfully improved motor function recovery in SCI model mice. Subsequently, [email protected] inhibited the uncontrollable inflammatory response after SCI by increasing M2 macrophage polarization; in addition, MNEVs released from [email protected] exerted neuroprotective effects by promoting axonal regeneration and remyelination. Collectively, these findings reveal a promising cell-free approach for suppressing inflammation and promoting neural regeneration to treat SCI.
研究领域:
神经科学
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再生医学
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药理学
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生物材料
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产品关联
DOI
高影响因子
ZOOLOGICAL RESEARCH
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2025
·Vol. 46
·期 4
·733
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IF 4.7
Bao-Guo Shen,Yuan Wen,Sheng-Jian Lu,Hong-Yuan Wei,Shu-Rui Huang,Guang-Ming Zhou,Wen-Tao Yan,Wen-Can Wu,Yi-Kui Zhang
In adult mammals, optic nerve injury leads to irreversible vision loss due to its extremely limited regenerative capacity. In contrast, adult zebrafish possess a robust capacity for spontaneous visual system regeneration, although the spatiotemporal coordination of recovery across the retina, optic nerve, and brain remains poorly understood. In the present study, the regenerative dynamics following optic nerve transection were systematically characterized in adult zebrafish over a 5 week period using hematoxylin-eosin staining, immunohistochemistry, transmission electron microscopy, single-cell RNA sequencing, and optokinetic response (OKR) behavioral assessments. At 1 week post-injury (1 wpi), retinal ganglion cell depletion was evident but showed significant recovery by 2 wpi. Concurrently, the injured optic nerve displayed a marked increase in diameter and cell number at 2 wpi, including widespread expression of proliferating cell nuclear antigen, consistent with heightened proliferative activity. Single-cell transcriptomic profiling at 2 wpi revealed five principal cell populations: fibroblasts, mural cells, immune cells, mature oligodendrocytes, and myelin-forming oligodendrocytes. By 4–5 wpi, remyelination within the optic nerve and re-establishment of synaptic architecture in the optic tectum were strongly correlated with functional restoration of OKR behavior. These findings provide a comprehensive spatiotemporal framework of visual pathway regeneration in zebrafish, establishing a valuable model for elucidating conserved mechanisms of neural repair with translational potential for human vision restoration.
研究领域:
神经再生
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发育生物学
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分子神经科学
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视觉系统
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转化医学研究
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2016
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IF 2.371
Zhijian Zhang,Zhengnan Li,Wenwen Deng,Qinghua He,Qiang Wang,Wentao Shi,Qian Chen,Wenjing Yang,Myron Spector,Aihua Gong,Jiangnan Yu,Ximing Xu
Many neurological diseases are closely associated with demyelination caused by pathological changes of oligodendrocytes . Although intrinsic remyelination occurs after injury, the regeneration efficiency of myelinating oligodendrocytes remains to be improved. Herein, we reported an initiative finding of employing a valuable cell source, namely neural crest-derived ectoderm mesenchymal stem cells (EMSCs), for promoting oligodendrocyte differentiation and maturation by co-culturing oligodendrocyte precursor cells (OPCs) with the EMSCs. The results demonstrated that the OPCs/EMSCs co-culture could remarkably increase the number and length of oligodendrocyte processes in comparison with the mono-cultured OPCs and non-contact OPCs/EMSCs transwell culture. Furthermore, the inhibition experiments revealed that the EMSCs-produced soluble factor Sonic hedgehog, gap junction protein connexin 43 and extracellular matrix molecule laminin accounted for the promoted OPC differentiation since inhibiting the function of anyone of the three proteins led to substantial retraction of processes and detachment of oligodendrocytes. Altogether, OPCs/EMSCs co-culture system could be a paradigmatic approach for promoting differentiation and maturation of oligodendrocytes, and EMSCs will be a promising cell source for the treatment of neurological diseases caused by oligodendrocyte death and demyelination.
研究领域:
神经科学
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干细胞生物学
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细胞神经科学
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分子生物学
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DOI
PubMed
高影响因子
ACS Nano
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2024
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IF 15.8
Junjie Shen,Yi Sun,Xuanzhe Liu,Yimin Chai,Chunyang Wang,Jia Xu
Peripheral nerve injury is a major societal concern. Black phosphorus (BP) has inherent advantages over cell-based therapies in regenerative medicine. However, controlling spontaneous degradation and size-dependent cytotoxicity remains challenging and poses difficulties for clinical translation. In this study, we constructed zero-dimensional BP quantum dots (QDs) modified with antioxidant β-carotene and comprehensively investigated them in Schwann cells (SCs) to elucidate their potential for peripheral nerve repair. In vitro experiments demonstrated that BPQD@β-carotene has an inappreciable toxicity and good biocompatibility, favoring neural regrowth, angiogenesis, and inflammatory regulation of SCs. Furthermore, the PI3K/Akt and Ras/ERK1/2 signaling pathways were activated in SCs at the genetic, protein, and metabolite levels. The BPQD@β-carotene-embedded GelMA/PEGDA scaffold enhanced functional recovery by promoting axon remyelination and regeneration and facilitating intraneural angiogenesis in peripheral nerve injury models of rats and beagle dogs. These results contribute to advancing knowledge of BP nanomaterials in tissue regeneration and show significant potential for application in translational medicine.
研究领域:
再生医学
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纳米技术
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神经科学
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生物医学工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Penghui Wang,Jiongming You,Guang Liu,Qiming Wang,Linjie Zhang,Xinwu Lu,Jinbao Qin,Zhihui Dong,Bingcheng Yi,Qun Huang
Biomaterial-assisted therapeutic strategies enable precise modulation to direct endogenous cellular responses and harness regenerative capabilities for nerve repair. However, achieving effective cellular engagement during nerve remodeling remains challenging. Herein, a novel composite nerve guidance conduit (NGC), the GelMA/PLys@PDA-Fe@PLCL conduit is developed by combining aligned poly( l -lactide-co-caprolactone) (PLCL) nanofibers modified with polydopamine (PDA), ferrous iron (Fe 3 ⁺), and polylysine (PLys) with aligned methacrylate-anhydride gelatin (GelMA) hydrogel nanofibers. PDA films exhibit strong adhesion and metal coordination properties, allowing Fe 3 ⁺ irons to chelate with phenolic hydroxyl groups of dopamine derivatives, forming a metal-phenolic network on PLCL. PLys molecules are then grafted onto PDA-Fe 3 ⁺ coating via Schiff base and Michael addition reactions. This multifunctional coating enhances surface roughness and zeta potential of PLCL nanofibers, imparts superhydrophilicity with anisotropic wetting behavior, and maintains wet tensile properties of substrates. In vitro studies show that the PLys@PDA-Fe coating significantly promotes aligned distribution of Schwann cells, improves cell adhesion and differentiation, and demonstrates notable antioxidant and anti-inflammatory properties. When implanted into nerve defects in rats, the multifunctional coating conduit combined with aligned GelMA hydrogel effectively accelerates axonal regeneration, remyelination, and angiogenesis, leading to enhanced motor function recovery. Overall, the GelMA/PLys@PDA-Fe@PLCL conduit presents a promising strategy for advancing peripheral nerve repair.
研究领域:
生物材料
·
组织工程
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神经科学
·
再生医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
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2019
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IF 2.679
Xiao-Yu Zhu,Sheng-Ya Guo,Bo Xia,Chun-Qi Li,Lei Wang,Yong-Hui Wang
RAR-related orphan receptor-γt (RORγt) directs differentiation of proinflammatory T helper 17 cells and is a potential therapeutic target for chronic autoimmune and inflammatory diseases including multiple sclerosis . In this study, zebrafish at days post fertilization treated with ethidium bromide (EB) at a concentration of 75 μM for 72 h were determined as the optimum conditions for the demyelination model development. Zebrafish motility was recorded automatically using a video-track motion detector and quantitative myelin assay was measured by FluoroMyelin staining. A well-known remyelination agent thyroxine (T4) was tested to confirm whether EB-induced motility and myelin damage could be rescued. Two RORγt lead inhibitors GSK805 and SR1001 were assessed for their therapeutic effects on remyelination, axon regeneration, motor neuron promotion and anti-inflammation. T4 significantly improved EB-induced motility dysfunction and myelin damage and promoted myelin basic protein (MBP) regeneration in the demyelinated zebrafish. GSK805 and SR1001 enhanced remyelination in a dose-dependent manner and promoted MBP regeneration. Both GSK805 and SR1001 markedly recovered EB-induced axon and motor neuron damage, and exhibited significantly inhibitory effects of neutrophil infiltration and macrophage recruitment. These results indicate that EB treatment can induce zebrafish demyelination; and the zebrafish demyelination model in combination with quantitative motility and myelin assays is a predictive, reproducible and relatively high throughput screening for rapidly in vivo identification of remyelination compounds and RORγt inhibitors.
研究领域:
神经科学
·
药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2021
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IF 5.811
Wu Wensi,Zhang Xiaojun,Zhou Jiaxin,Yang Hongmei,Chen Junjun,Zhao Le,Zhong Junying,Lin Wei-jye,Wang Zhi
Perioperative neurocognitive disorder (PND) leads to progressive deterioration of cognitive function, especially in aged patients. Demyelination is closely associated with cognitive dysfunction. However, the relationship between PND and demyelination remains unclear. Here we showed that demyelination was related to the pathogenesis of PND. Clemastine, an antihistamine with potency in remyelination, was predicted to have a potential therapeutic effect on PND by next-generation sequencing and bioinformatics in our previous study. In the present study, it was given at 10 mg/kg per day for 2 weeks to evaluate the effects on PND in aged mice. We found that clemastine ameliorated PND and reduced the expression levels of inflammatory factors such as tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β). Further investigation suggested clemastine increased the expression of oligodendrocyte transcription factor 2 (OLIG2) and myelin basic protein (MBP) to enhance remyelination by inhibiting the overactivation of the WNT/β-catenin pathway. At the same time, the expression of post-synaptic density protein 95 (PSD95, or DLG4), brain-derived neurotrophic factor (BDNF), synaptosomal-associated protein 25 (SNAP25) and neuronal nuclei (NEUN) were also improved. Our results suggested that clemastine might be a therapy for PND caused by anesthetic and surgical factors in aged patients.
研究领域:
神经科学
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药理学
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老年医学
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分子生物学
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DOI
PubMed
高影响因子
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