114 results on '"Lü, He-Zuo"'
Search Results
2. Exosomes derived from vMIP-II-Lamp2b gene-modified M2 cells provide neuroprotection by targeting the injured spinal cord, inhibiting chemokine signals and modulating microglia/macrophage polarization in mice
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Fu, Gui-Qiang, Wang, Yang-Yang, Xu, Yao-Mei, Bian, Ming-Ming, Zhang, Lin, Yan, Hua-Zheng, Gao, Jian-Xiong, Li, Jing-Lu, Chen, Yu-Qing, Zhang, Nan, Ding, Shu-Qin, Wang, Rui, Li, Jiang-Yan, Hu, Jian-Guo, and Lü, He-Zuo
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- 2024
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3. Effect of morroniside on the transcriptome profiles of rat in injured spinal cords
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Shi, Yu-Jiao, Sheng, Wen-Jie, Xue, Meng-Tong, Duan, Fei-Xiang, Shen, Lin, Ding, Shu-Qin, Wang, Qi-Yi, Wang, Rui, Lü, He-Zuo, and Hu, Jian-Guo
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- 2022
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4. Spatio-temporal expression of Hexokinase-3 in the injured female rat spinal cords
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Lin, Yu-Hong, Wu, Yan, Wang, Ying, Yao, Zong-Feng, Tang, Jie, Wang, Rui, Shen, Lin, Ding, Shu-Qin, Hu, Jian-Guo, and Lü, He-Zuo
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- 2018
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5. CRID3, a blocker of apoptosis associated speck like protein containing a card, ameliorates murine spinal cord injury by improving local immune microenvironment
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Chen, Yu-Qing, Wang, Sai-Nan, Shi, Yu-Jiao, Chen, Jing, Ding, Shu-Qin, Tang, Jie, Shen, Lin, Wang, Rui, Ding, Hai, Hu, Jian-Guo, and Lü, He-Zuo
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- 2020
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6. Adoptive transfer of M2 macrophages promotes locomotor recovery in adult rats after spinal cord injury
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Ma, Shan-Feng, Chen, Yue-Juan, Zhang, Jing-Xing, Shen, Lin, Wang, Rui, Zhou, Jian-Sheng, Hu, Jian-Guo, and Lü, He-Zuo
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- 2015
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7. Schwann cells induce Proliferation and Migration of Oligodendrocyte Precursor Cells Through Secretion of PDGF-AA and FGF-2
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Chen, Yue-Juan, Zhang, Jing-Xing, Shen, Lin, Qi, Qi, Cheng, Xiao-Xin, Zhong, Zheng-Rong, Jiang, Zhi-Quan, Wang, Rui, Lü, He-Zuo, and Hu, Jian-Guo
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- 2015
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8. JNK Is Necessary for Oligodendrocyte Precursor Cell Proliferation Induced by the Conditioned Medium from B104 Neuroblastoma Cells
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Zhang, Jing-Xing, Feng, Yi-Fan, Qi, Qi, Shen, Lin, Wang, Rui, Zhou, Jian-Sheng, Lü, He-Zuo, and Hu, Jian-Guo
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- 2014
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9. Differential effects of myelin basic protein-activated Th1 and Th2 cells on the local immune microenvironment of injured spinal cord
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Hu, Jian-Guo, Shi, Ling-Ling, Chen, Yue-Juan, Xie, Xiu-Mei, Zhang, Nan, Zhu, An-You, Jiang, Zheng-Song, Feng, Yi-Fan, Zhang, Chen, Xi, Jin, and Lü, He-Zuo
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- 2016
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10. The Molecular Events Involved in Oligodendrocyte Precursor Cell Proliferation Induced by the Conditioned Medium from B104 Neuroblastoma Cells
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Hu, Jian-Guo, Wu, Xing-Jun, Feng, Yi-Fan, Xi, Gang-ming, Deng, Ling-Xiao, Wang, Zhen-Huan, Wang, Rui, Shen, Lin, Zhou, Jian-Sheng, and Lü, He-Zuo
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- 2013
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11. Effects of Olig2-Overexpressing Neural Stem Cells and Myelin Basic Protein-Activated T Cells on Recovery from Spinal Cord Injury
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Hu, Jian-Guo, Shen, Lin, Wang, Rui, Wang, Qi-Yi, Zhang, Chen, Xi, Jin, Ma, Shan-Feng, Zhou, Jian-Sheng, and Lü, He-Zuo
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- 2012
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12. PDGF-AA Mediates B104CM-Induced Oligodendrocyte Precursor Cell Differentiation of Embryonic Neural Stem Cells Through Erk, PI3K, and p38 Signaling
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Hu, Jian-Guo, Wang, Yan-Xia, Wang, Hong-Ju, Bao, Ming-Sheng, Wang, Zhen-Huan, Ge, Xin, Wang, Feng-Chao, Zhou, Jian-Sheng, and Lü, He-Zuo
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- 2012
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13. Olig1 and ID4 interactions in living cells visualized by bimolecular fluorescence complementation technique
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Guo, Shu-Jun, Hu, Jian-Guo, Zhao, Bao-Ming, Shen, Lin, Wang, Rui, Zhou, Jian-Sheng, and Lü, He-Zuo
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- 2011
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14. Effects of autoimmunity on recovery of function in adult rats following spinal cord injury
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Lü, He-Zuo, Xu, Liang, Zou, Jian, Wang, Yan-Xia, Ma, Zheng-Wen, Xu, Xiao-Ming, and Lu, Pei-Hua
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- 2008
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15. Long-term Fate of Allogeneic Neural Stem Cells Following Transplantation into Injured Spinal Cord
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Xu, Liang, Xu, Chao-jin, Lü, He-Zuo, Wang, Yan-Xia, Li, Ying, and Lu, Pei-Hua
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- 2010
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16. Atractylenolide III ameliorates spinal cord injury in rats by modulating microglial/macrophage polarization.
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Xue, Meng‐Tong, Sheng, Wen‐Jie, Song, Xue, Shi, Yu‐Jiao, Geng, Zhi‐Jun, Shen, Lin, Wang, Rui, Lü, He‐Zuo, and Hu, Jian‐Guo
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MICROGLIA ,SPINAL cord injuries ,MACROPHAGES ,INFLAMMATORY mediators ,RATS ,SPINAL cord - Abstract
Background: Inflammatory reactions induced by spinal cord injury (SCI) are essential for recovery after SCI. Atractylenolide III (ATL‐III) is a natural monomeric herbal bioactive compound that is mainly derived in Atractylodes macrocephala Koidz and has anti‐inflammatory and neuroprotective effects. Objective: Here, we speculated that ATL‐III may ameliorate SCI by modulating microglial/macrophage polarization. In the present research, we focused on investigating the role of ATL‐III on SCI in rats and explored the potential mechanism. Methods: The protective and anti‐inflammatory effects of ATL‐III on neuronal cells were examined in a rat SCI model and lipopolysaccharide (LPS)‐stimulated BV2 microglial line. The spinal cord lesion area, myelin integrity, and surviving neurons were assessed by specific staining. Locomotor function was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale, grid walk test, and footprint test. The activation and polarization of microglia/macrophages were assessed by immunohistofluorescence and flow cytometry. The expression of corresponding inflammatory factors from M1/M2 and the activation of relevant signaling pathways were assessed by Western blotting. Results: ATL‐III effectively improved histological and functional recovery in SCI rats. Furthermore, ATL‐III promoted the transformation of M1 into M2 and attenuated the activation of microglia/macrophages, further suppressing the expression of corresponding inflammatory mediators. This effect may be partly mediated by inhibition of neuroinflammation through the NF‐κB, JNK MAPK, p38 MAPK, and Akt pathways. Conclusion: This study reveals a novel effect of ATL‐III in the regulation of microglial/macrophage polarization and provides initial evidence that ATL‐III has potential therapeutic benefits in SCI rats. [ABSTRACT FROM AUTHOR]
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- 2022
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17. Neuroprotective Effects of the Pannexin-1 Channel Inhibitor: Probenecid on Spinal Cord Injury in Rats.
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Qi, Qi, Wang, Xiao-Xuan, Li, Jing-Lu, Chen, Yu-Qing, Chang, Jian-Rong, Xi, Jin, Lü, He-Zuo, and Zhang, Yu-Xin
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SPINAL cord injuries ,INTERLEUKIN-1 receptor antagonist protein ,INFLAMMASOMES ,MOTOR neurons ,NEUROPROTECTIVE agents ,RATS - Abstract
Proinflammatory immune cell subsets constitute the majority in the local microenvironment after spinal cord injury (SCI), leading to secondary pathological injury. Previous studies have demonstrated that inflammasomes act as an important part of the inflammatory process after SCI. Probenecid, an inhibitor of the Pannexin-1 channel, can inhibit the activation of inflammasomes. This article focuses on the effects of probenecid on the local immune microenvironment, histopathology, and behavior of SCI. Our data show that probenecid inhibited the expression and activation of nucleotide-binding oligomerization domain receptor pyrindomain-containing 1 (NLRP1), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1, interleukin-1β (IL-1β), and caspase-3 proteins associated with inflammasomes, thereby suppressing the proportion of M1 cells. And consequently, probenecid reduced the lesion area and demyelination in SCI. Moreover, the drug increased the survival of motor neurons, which resulted in tissue repair and improved locomotor function in the injured SC. Altogether, existing studies indicated that probenecid can alleviate inflammation by blocking Pannexin-1 channels to inhibit the expression of caspase-1 and IL-1β, which in turn restores the balance of immune cell subsets and exerts neuroprotective effects in rats with SCI. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Feature article: Neuroprotective effects of P7C3 against spinal cord injury in rats
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Duan, Fei-Xiang, Shi, Yu-Jiao, Chen, Jing, Ding, Shu-Qin, Wang, Feng-Chao, Tang, Jie, Wang, Rui, Shen, Lin, Xi, Jin, Qi, Qi, Lü, He-Zuo, and Hu, Jian-Guo
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Neurons ,Rats, Sprague-Dawley ,Oligodendroglia ,Neuroprotective Agents ,Spinal Cord ,Carbazoles ,Animals ,Female ,Motor Activity ,NAD ,Spinal Cord Injuries ,Original Research ,Rats - Abstract
Spinal cord injury (SCI), a serious neurological disease, has few therapeutic interventions. A small molecule, P7C3, has been confirmed to play a role in neuroprotection of some neurological diseases. But the effect of P7C3 on acute SCI has not been investigated. Here, we observed the therapeutic effect of P7C3 for alleviating the neurological damage by direct subcutaneous injection after SCI once daily for 7 or 14 days in a rat model. The locomotion and histopathological changes were evaluated. Our results demonstrated that P7C3 treatment contributed to functional recovery and tissue repair following SCI. Improved locomotor function with P7C3 treatment was correlated with increased survival of neurons and oligodendrocytes (OLs) and proliferation of OLs and their progenitors, which resulted in tissue repair and myelination in the injured SC. P7C3 treatment also restored the nicotinamide adenine dinucleotide level in the SC, which was reduced by SCI. These results suggest that P7C3 plays a role in improving neurological outcome following SCI. IMPACT STATEMENT: Spinal cord injury (SCI), a serious neurological disease, has few therapeutic interventions. This study confirms for the first time that P7C3 is conducive to functional recovery and tissue repair after SCI. P7C3 treatment can rescue the nicotinamide adenine dinucleotide level of the injured spinal cord, which results in more survival of neurons and oligodendrocytes (OLs) and proliferation of OLs and their progenitors, and thus increase myelination and tissue repair. This result indicates that P7C3 plays a role in improving neurological outcome following SCI.
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- 2019
19. Glutamine synthetase down-regulation reduces astrocyte protection against glutamate excitotoxicity to neurons
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Zou, Jian, Wang, Yan-Xia, Dou, Fang-Fang, Lü, He-Zuo, Ma, Zheng-Wen, Lu, Pei-Hua, and Xu, Xiao-Ming
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- 2010
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20. Cyclosporin A increases recovery after spinal cord injury but does not improve myelination by oligodendrocyte progenitor cell transplantation
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Wang Feng-Chao, Zhou Jian-Sheng, Wang Yan-Xia, Lü He-Zuo, and Hu Jian-Guo
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurophysiology and neuropsychology ,QP351-495 - Abstract
Abstract Background Transplantation of oligodendrocyte precursor cells (OPCs) is an attractive therapy for demyelinating diseases. Cyclosporin A (CsA) is one of the foremost immunosuppressive agents and has widespread use in tissue and cell transplantation. However, whether CsA affects survival and differentiation of engrafted OPCs in vivo is unknown. In this study, the effect of CsA on morphological, functional and immunological aspects, as well as survival and differentiation of engrafted OPCs in injured spinal cord was explored. Results We transplanted green fluorescent protein (GFP) expressed OPCs (GFP-OPCs) into injured spinal cords of rats treated with or without CsA (10 mg/kg). Two weeks after cell transplantation, more GFP-positive cells were found in CsA-treated rats than that in vehicle-treated ones. However, the engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes in both groups. In the CsA-treated group, a significant decrease in spinal cord lesion volume along with increase in spared myelin and neurons were found compared to the control group. Such histological improvement correlated well with an increase in behavioral recovery. Further study suggested that CsA treatment could inhibit infiltration of T cells and activation of resident microglia and/or macrophages derived from infiltrating monocytes in injured spinal cords, which contributes to the survival of engrafted OPCs and repair of spinal cord injury (SCI). Conclusions These results collectively indicate that CsA can promote the survival of engrafted OPCs in injured spinal cords, but has no effect on their differentiation. The engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes. The beneficial effect of CsA on SCI and the survival of engrafted cells may be attributed to its neuroprotective effect.
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- 2010
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21. Chondroitin sulfate proteoglycans regulate the growth, differentiation and migration of multipotent neural precursor cells through the integrin signaling pathway
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Lü He-Zuo, Li Ying, Wang Yan-Xia, Fu Sai-Li, Gu Wen-Li, Xu Xiao-Ming, and Lu Pei-Hua
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurophysiology and neuropsychology ,QP351-495 - Abstract
Abstract Background Neural precursor cells (NPCs) are defined by their ability to proliferate, self-renew, and retain the potential to differentiate into neurons and glia. Deciphering the factors that regulate their behaviors will greatly aid in their use as potential therapeutic agents or targets. Chondroitin sulfate proteoglycans (CSPGs) are prominent components of the extracellular matrix (ECM) in the central nervous system (CNS) and are assumed to play important roles in controlling neuronal differentiation and development. Results In the present study, we demonstrated that CSPGs were constitutively expressed on the NPCs isolated from the E16 rat embryonic brain. When chondroitinase ABC was used to abolish the function of endogenous CSPGs on NPCs, it induced a series of biological responses including the proliferation, differentiation and migration of NPCs, indicating that CSPGs may play a critical role in NPC development and differentiation. Finally, we provided evidence suggesting that integrin signaling pathway may be involved in the effects of CSPGs on NPCs. Conclusion The present study investigating the influence and mechanisms of CSPGs on the differentiation and migration of NPCs should help us to understand the basic biology of NPCs during CNS development and provide new insights into developing new strategies for the treatment of the neurological disorders in the CNS.
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- 2009
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22. Effect of VX-765 on the transcriptome profile of mice spinal cords with acute injury.
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Chen, Jing, Chen, Yu-Qing, Wang, Sai-Nan, Duan, Fei-Xiang, Shi, Yu-Jiao, Ding, Shu-Qin, Hu, Jian-Guo, and Lü, He-Zuo
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SPINAL cord injuries ,FOCAL adhesions ,WESTERN immunoblotting ,MICE ,GENE ontology ,EXTRACELLULAR signal-regulated kinases - Abstract
Previous studies have shown that caspase-1 plays an important role in the acute inflammatory response of spinal cord injury (SCI). VX-765, a novel and irreversible caspase-1 inhibitor, has been reported to effectively intervene in inflammation. However, the effect of VX-765 on genome-wide transcription in acutely injured spinal cords remains unknown. Therefore, in the present study, RNA-sequencing (RNA-Seq) was used to analyze the effect of VX-765 on the local expression of gene transcription 8 h following injury. The differentially expressed genes (DEGs) underwent enrichment analysis of functions and pathways by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, respectively. Parallel analysis of western blot confirmed that VX-765 can effectively inhibit the expression and activation of caspase-1. RNA-Seq showed that VX-765 treatment resulted in 1,137 upregulated and 1,762 downregulated DEGs. These downregulated DEGs and their associated signaling pathways, such as focal adhesion, cytokine-cytokine receptor interaction, leukocyte transendothelial migration, extracellular matrix-receptor interaction, phosphatidylinositol 3-kinase-protein kinase B, Rap1 and hypoxia inducible factor-1 signaling pathway, are mainly associated with inflammatory response, local hypoxia, macrophage differentiation, adhesion migration and apoptosis of local cells. This suggests that the application of VX-765 in the acute phase can improve the local microenvironment of SCI by inhibiting caspase-1. However, whether VX-765 can be used as a therapeutic drug for SCI requires further exploration. The sequence data have been deposited into the Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra/PRJNA548970). [ABSTRACT FROM AUTHOR]
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- 2020
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23. Highlight article: Identification of serum exosomal microRNAs in acute spinal cord injured rats.
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Ding, Shu-Qin, Chen, Jing, Wang, Sai-Nan, Duan, Fei-Xiang, Chen, Yu-Qing, Shi, Yu-Jiao, Hu, Jian-Guo, and Lü, He-Zuo
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- 2019
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24. Effect of M2 macrophage adoptive transfer on transcriptome profile of injured spinal cords in rats.
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Chen, Jing, Wu, Yan, Duan, Fei-Xiang, Wang, Sai-Nan, Guo, Xue-Yan, Ding, Shu-Qin, Zhou, Ji-Hong, Hu, Jian-Guo, and Lü, He-Zuo
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- 2019
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25. Subcutaneous Administration of PDGF-AA Improves the Functional Recovery After Spinal Cord Injury.
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Guo, Xue-Yan, Duan, Fei-Xiang, Chen, Jing, Wang, Ying, Wang, Rui, Shen, Lin, Qi, Qi, Jiang, Zhi-Quan, Zhu, An-You, Xi, Jin, Lü, He-Zuo, and Hu, Jian-Guo
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SPINAL cord injuries ,PLATELET-derived growth factor ,OLIGODENDROGLIA ,SUBCUTANEOUS infusions ,PROGENITOR cells - Abstract
Previous studies by our group have demonstrated that the transplantation of exogenous platelet-derived growth factor (PDGF)-AA-overexpressing oligodendrocyte progenitor cells (OPCs) promotes tissue repair and recovery of neurological function in a rat model of spinal cord injury (SCI). However, it remains unclear whether treatment with PDGF-AA also affects endogenous oligodendrocytes (OLs) or even neurons, thus promoting further functional recovery after SCI. In the present study, we evaluated the therapeutic potential of PDGF-AA treatment by direct subcutaneous injection of PDGF-AA immediately after SCI. We demonstrated that PDGF-AA injection resulted in increased tissue sparing, myelination and functional recovery in rats following SCI. Further experimentation confirmed that PDGF-AA increased the survival of endogenous OPCs and OLs, and promoted the proliferation of OPCs and their differentiation into OLs. Moreover, PDGF-AA also protected motor neurons from death in the injured spinal cord. These results indicated that PDGF-AA administration may be an effective treatment for SCI. [ABSTRACT FROM AUTHOR]
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- 2019
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26. Increased ceruloplasmin expression caused by infiltrated leukocytes, activated microglia, and astrocytes in injured female rat spinal cords.
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Wu, Yan, Shen, Lin, Wang, Rui, Tang, Jie, Ding, Shu‐Qin, Wang, Sai‐Nan, Guo, Xue‐Yan, Hu, Jian‐Guo, and Lü, He‐Zuo
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- 2018
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27. Expression and Cellular Localization of IFITM1 in Normal and Injured Rat Spinal Cords.
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Wang, Ying, Lin, Yu-Hong, Wu, Yan, Yao, Zong-Feng, Tang, Jie, Shen, Lin, Wang, Rui, Ding, Shu-Qin, Hu, Jian-Guo, and Lü, He-Zuo
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SPINAL cord ,MEMBRANE proteins ,CYTOKINES ,MESSENGER RNA ,OLIGODENDROGLIA - Abstract
Interferon-induced transmembrane protein 1 (IFITM1) is a member of the IFITM family that is associated with some acute-phase cytokine-stimulated response. Recently, we demonstrated that IFITM1 was significantly upregulated in the injured spinal cords at the mRNA level. However, its expression and cellular localization at the protein level is still unclear. Here, a rat model of spinal cord injury (SCI) was performed to investigate the spatio-temporal expression of IFITM1 after SCI. IFITM1 mRNA and protein were assessed by quantitative reverse transcription-PCR and western blot, respectively. IHC was used to identify its cellular localization. We revealed that IFITM1 could be found in sham-opened spinal cords and gradually increased after SCI. It reached peak at 7 and 14 days postinjury (dpi) and still maintained at a relatively higher level at 28 dpi. IHC showed that IFITM1 expressed in GFAP
+ and APC+ cells in sham-opened spinal cords. After SCI, in addition to the above-mentioned cells, it could also be found in CD45+ and CD68+ cells, and its expression in CD45+ , CD68+ , and GFAP+ cells was increased significantly. These results demonstrate that IFITM1 is mainly expressed in astrocytes and oligodendroglia in normal spinal cords, and could rapidly increase in infiltrated leukocytes, activated microglia, and astrocytes after SCI. [ABSTRACT FROM AUTHOR]- Published
- 2018
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28. Temporal kinetics of CD8+CD28+ and CD8+CD28− T lymphocytes in the injured rat spinal cord.
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Wu, Yan, Lin, Yu‐Hong, Shi, Ling‐Ling, Yao, Zong‐Feng, Xie, Xiu‐Mei, Jiang, Zheng‐Song, Tang, Jie, Hu, Jian‐Guo, and Lü, He‐Zuo
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- 2017
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29. Temporal kinetics of macrophage polarization in the injured rat spinal cord.
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Chen, Yue‐Juan, Zhu, Hai, Zhang, Nan, Shen, Lin, Wang, Rui, Zhou, Jian‐Sheng, Hu, Jian‐Guo, and Lü, He‐Zuo
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- 2015
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30. Passive Immunization With Myelin Basic Protein Activated T Cells Suppresses Axonal Dieback but Does Not Promote Axonal Regeneration Following Spinal Cord Hemisection in Adult Rats.
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Wang, Hong-Ju, Hu, Jian-Guo, Shen, Lin, Wang, Rui, Wang, Qi-Yi, Zhang, Chen, Xi, Jin, Zhou, Jian-Sheng, and Lü, He-Zuo
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MYELIN basic protein ,T cells ,SPINAL cord injuries ,CENTRAL nervous system ,BIOTIN ,PYRAMIDAL tract ,NEUROPROTECTIVE agents - Abstract
The previous studies suggested that some subpopulations of T lymphocytes against central nervous system (CNS) antigens, such as myelin basic protein (MBP), are neuroprotective. But there were few reports about the effect of these T cells on axon regeneration. In this study, the neonatally thymectomied (Tx) adult rats which contain few T lymphocytes were subjected to spinal cord hemisection and then passively immunized with MBP-activated T cells (MBP-T). The regeneration and dieback of transected axons of cortico-spinal tract (CST) were detected by biotin dextran amine (BDA) tracing. The behavioral assessments were performed using the Basso, Beattie, and Bresnahan locomotor rating scale. We found that passive transferring of MBP-T could attenuate axonal dieback. However, no significant axon regeneration and behavioral differences were observed among the normal, Tx and sham-Tx (sTx) rats with or without MBP-T passive immunization. These results indicate that passive transferring of MBP-T cells can attenuate axonal dieback and promote neuroprotection following spinal cord injury (SCI), but may not promote axon regeneration. [ABSTRACT FROM AUTHOR]
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- 2012
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31. Lower concentrations of methyl-β-cyclodextrin combined with interleukin-2 can preferentially induce activation and proliferation of natural killer cells in human peripheral blood
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Lü, He-Zuo, Zhu, An-You, Chen, Yong, Tang, Jie, and Li, Bai-Qing
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CYCLODEXTRINS , *INTERLEUKIN-2 , *KILLER cells , *CELL proliferation , *LYMPHOCYTES , *BLOOD testing , *LYMPHOKINES - Abstract
Abstract: Previous studies have demonstrated that high concentrations of methyl-β-cyclodextrin (MβCD, 10–15 mM) can interfere with the formation of lipid rafts and inhibit activation of lymphocytes. In this report, we determined that lower concentrations of MβCD (1–4 mM) could accelerate the proliferation of lymphocytes in human peripheral blood mononuclear cells (PBMCs). In the expanded cells, CD3-CD56+ natural killer (NK) cells were the dominant subpopulation, and a significant dose–effect relationship existed between the proportion of NK cells and the concentration of MβCD. In the groups treated with 3–4 mM MβCD, the proportions of NK cells reached a level of more than 60%. When PBMCs were treated with MβCD, CD69 was more preferentially expressed on CD3-CD56+ cells than on CD3+ cells at 48 and 72 hours. The expression of CD25 had no distinct difference at 48 hours, but when recombinant human interleukin-2 (IL-2) was added for a further 24 hours, it was also preferentially expressed on NK cells. MβCD and IL-2 synergistically could also induce interferon-γ (IFN-γ) production in CD56+ human PBMCs. Mechanistic studies revealed that IFN-γ production in response to MβCD plus IL-2 was IL-12 independent but depended on endogenous IL-18 and IL-1β, and CD56+CD14+ dendritic cell-like cells and B cells might mediate the ability of MβCD to activate NK cells. The MβCD-activated NK cells also had high cytotoxicity against the natural killer cell–sensitive K562 cells or lymphokine-activated killer cell–sensitive DAUDI cells in vitro. These studies indicated that lower concentrations of MβCD combined with IL-2 can preferentially induce activation and proliferation of NK cells in PBMCs. [Copyright &y& Elsevier]
- Published
- 2011
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32. Effect of HMG-CoA reductase inhibitors on activation of human γδT cells induced by Mycobacterium tuberculosis antigens.
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Lü, He-Zuo and Li, Bai-Qing
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MYCOBACTERIUM tuberculosis , *PHOSPHORYLATION , *AMINO acids , *ISOPENTENOIDS , *LUNG diseases - Abstract
Lipid rafts are cholesterol-enriched microdomains which act as a platform for the initiation of T-cell activation. To investigate effect of endogenous cholesterol on lipid rafts formation and activation of γδT cells, human peripheral blood mononuclear cells were stimulated in vitro with Mycobacterium tuberculosis antigens (Mtb-Ag). Lovastatin and fluvastatin, two 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) inhibitors, were used to block endogenous cholesterol biosynthesis. The expression of ganglioside GM1 (GM1), a lipid rafts marker, and CD69, an activation marker, and the level of tyrosine phosphorylation in γδT cells were measured by flow cytometry. The expression and aggregation of GM1 were also detected with laser confocal microscopy. We found that lovastatin and fluvastatin could obviously inhibit tyrosine phosphorylation and expression of GM1 and CD69 in γδT cells induced by Mtb-Ag. These results collectively indicated that HMGCR inhibitors might interfere with the formation of lipid rafts and inhibit the activation of γδT cells induced by Mtb-Ag. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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33. Serum exosomal microRNA transcriptome profiling in subacute spinal cord injured rats.
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Ding, Shu-Qin, Chen, Yu-Qing, Chen, Jing, Wang, Sai-Nan, Duan, Fei-Xiang, Shi, Yu-Jiao, Hu, Jian-Guo, and Lü, He-Zuo
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EXOSOMES , *SPINAL cord , *PERIPHERAL circulation , *MICRORNA , *BODY fluids , *CENTRAL nervous system - Abstract
MicroRNAs (miRNAs) are involved in a series of pathology of spinal cord injury (SCI). Although, locally expressed miRNAs have advantages in studying the pathological mechanism, they cannot be used as biomarkers. The "free circulation" miRNAs can be used as biomarkers, but they have low concentration and poor stability in body fluids. Exosomal miRNAs in body fluids have many advantages comparing with free miRNAs. Therefore, we hypothesized that the specific miRNAs in the central nervous system might be transported to the peripheral circulation and concentrated in exosomes after injury. Using next-generation sequencing, miRNA profiles in serum exosomes of sham and subactue SCI rats were analyzed. The results showed that SCI can lead to changes of serum exosomal miRNAs. These changed miRNAs and their associated signaling pathways may explain the pathological mechanism of suacute SCI. More importantly, we found some valuable serum exosomal miRNAs for diagnosis and prognosis of SCI. • Serum exosomes of sham and subactue SCI rats were isolated and identified. • Serum exosomal microRNA transcriptome profiling in subacute spinal cord injured rats is investigated. • The changed miRNAs and their associated signaling pathways have been systematically determined. • Our results will provide a basis for the pathological mechanism, diagnosis and prognosis of SCI. [ABSTRACT FROM AUTHOR]
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- 2020
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34. Transcriptome profile of rat genes in bone marrow-derived macrophages at different activation statuses by RNA-sequencing.
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Guo, Xue-Yan, Wang, Sai-Nan, Wu, Yan, Lin, Yu-Hong, Tang, Jie, Ding, Shu-Qin, Shen, Lin, Wang, Rui, Hu, Jian-Guo, and Lü, He-Zuo
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MACROPHAGE activation , *GENES , *RATS , *GENE expression , *MACROPHAGES , *BONES - Abstract
The underlying mechanisms of macrophage polarization have been detected by genome-wide transcriptome analysis in a variety of mammals. However, the transcriptome profile of rat genes in bone marrow-derived macrophages (BMM) at different activation statuses has not been reported. Therefore, we performed RNA-Sequencing to identify gene expression signatures of rat BMM polarized in vitro with different stimuli. The differentially expressed genes (DEGs) among unactivated (M0), classically activated pro-inflammatory (M1), and alternatively activated anti-inflammatory macrophages (M2) were analyzed by using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. In this study, not only we have identified the changes of global gene expression in rat M0, M1 and M2, but we have also made clear systematically the key genes and signaling pathways in the differentiation process of M0 to M1 and M2. These will provide a foundation for future researches of macrophage polarization. • The transcriptome profile of rat genes in bone marrow-derived macrophages at different activation statuses is investigated. • The global gene expression in rat M0, M1 and M2 has been described. • The key genes and signaling pathways in the differentiation process of M0 to M1 and M2 have been systematically determined. • Our results will provide a basis for future researches of macrophage polarization. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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35. Co-transplantation of MRF-overexpressing oligodendrocyte precursor cells and Schwann cells promotes recovery in rat after spinal cord injury.
- Author
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Xie, Xiu-Mei, Shi, Ling-Ling, Shen, Lin, Wang, Rui, Qi, Qi, Wang, Qi-Yi, Zhang, Lun-Jun, Lü, He-Zuo, and Hu, Jian-Guo
- Subjects
- *
SPINAL cord injuries , *OLIGODENDROGLIA , *MYELIN regulatory factor , *SCHWANN cells , *MYELINATION , *IN vitro studies , *IN vivo studies , *LABORATORY rats - Abstract
Oligodendrocyte (OL) replacement is a promising treatment strategy for spinal cord injury (SCI). However, the poor survival of transplanted OLs or their precursors and inhibition of axonal regeneration are two major challenges with this approach. Our previous study showed that Schwann cells (SCs) promoted survival, proliferation, and migration of transplanted OL progenitor cells (OPCs) and neurological recovery. Remyelination is an important basis for functional recovery following spinal cord injury. It has been reported that myelin gene regulatory factor (MRF), a transcriptional regulator which specifically is expressed in postmitotic OLs within the CNS, is essential for OL maturation and CNS myelination. In the present study, we investigated whether co-transplantation of MRF-overexpressing OPCs (MRF-OPCs) and SCs could improve functional recovery in a rat model of contusional SCI. MRF overexpression had no effect on OPC survival or migration, but stimulated the differentiation of OPCs both in vitro and in vivo. Co-transplantation of MRF-OPCs and SCs increased myelination and tissue repair after SCI, leading to the recovery of neurological function. These results indicate that co-transplantation of MRF-OPCs and SCs may be an effective treatment strategy for SCI. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
36. The neuroprotective role of morroniside against spinal cord injury in female rats.
- Author
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Duan, Fei-Xiang, Shi, Yu-Jiao, Chen, Jing, Song, Xue, Shen, Lin, Qi, Qi, Ding, Shu-Qin, Wang, Qi-Yi, Wang, Rui, Lü, He-Zuo, and Hu, Jian-Guo
- Subjects
- *
SPINAL cord injuries , *SUPERIOR colliculus , *REACTIVE oxygen species , *RATS , *NEUROPROTECTIVE agents , *DISABILITIES - Abstract
Spinal cord injury (SCI) is a disabling condition that often leads to permanent neurological deficits without an effective treatment. Reactive oxygen species (ROS) produced during oxidative stress play a vital role in the pathogenesis following SCI. The antioxidant morroniside is the main active component of the Chinese medicine Cornus officinalis. In recent years, it has been reported that morroniside has therapeutic effects on damage to multiple organs mediated by oxidative damage, but the effect of morroniside on SCI has not been reported. The purpose of this study was therefore to assess the therapeutic effect of morroniside on SCI, and to identify its underlying mechanism by direct intragastric administration immediately after SCI. Our study showed that morroniside treatment improved the functional recovery of rats following SCI. This behavioral improvement was associated with the higher survival in neurons and oligodendrocytes following SCI, which increased the capacity of injured spinal cord (SC) to form myelin and repair tissue, eventually contributing to improved neurological outcome. Furthermore, our study found that oxygen free radicals increased and antioxidant enzyme activity decreased in the injured SC. Interestingly, morroniside treatment decreased oxygen free radical levels and increased antioxidant enzyme activities. Together, our results suggested that morroniside may be an effective treatment for improving outcomes following SCI, and that its antioxidant activity may be one of the mechanisms by which morroniside exerts neuroprotective effects on SCI. • Morroniside significantly promoted the histological recoveries of injured SC tissue and locomotor function in rats after SCI. • Morroniside inhibited oxidative stress and promoted the survival of neurons and OLs in injured SC. • Morroniside may be an effective treatment for improving outcomes following SCI. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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- View/download PDF
37. The beneficial effect of α-lipoic acid on spinal cord injury repair in rats is mediated through inhibition of oxidative stress: A transcriptomic analysis.
- Author
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Bian MM, Xu YM, Zhang L, Yan HZ, Gao JX, Fu GQ, Wang YY, and Lü HZ
- Abstract
Background: Oxidative stress is a crucial factor contributing to the occurrence and development of secondary damage in spinal cord injuries (SCI), ultimately impacting the recovery process. α-lipoic acid (ALA) exhibits potent antioxidant properties, effectively reducing secondary damage and providing neuroprotective benefits. However, the precise mechanism by which ALA plays its antioxidant role remains unknown., Methods: We established a model of moderate spinal cord contusion in rats. Experimental rats were randomly divided into 3 distinct groups: the sham group, the model control group (SCI_Veh), and the ALA treatment group (SCI_ALA). The sham group rats were exposed only to the SC without contusion injury. Rats belonging to SCI_Veh group were not administered any treatment after SCI. Rats of SCI_ALA group were intraperitoneally injected with the corresponding volume of ALA according to body weight for three consecutive days after the surgery. Subsequently, three days after SCI, spinal cord samples were obtained from three groups of rats: the sham group, model control group, and administration group. Thereafter, total RNA was extracted from the samples and the expression of three sets of differential genes was analyzed by transcriptome sequencing technology. Real-time PCR was used to verify the sequencing results. The impact of ALA on oxidative stress in rats following SCI was assessed by measuring their total antioxidant capacity and hydrogen peroxide (H
2 O2 ) content. The effects of ALA on rat recovery following SCI was investigated through Beattie and Bresnahan (BBB) score and footprint analysis., Results: The findings from the transcriptome sequencing analysis revealed that the model control group had 2975 genes with altered expression levels when compared to the ALA treatment group. Among these genes, 1583 were found to be upregulated while 1392 were down-regulated. Gene ontology (GO) displayed significant enrichment in terms of functionality, specifically in oxidative phosphorylation, oxidoreductase activity, and signaling receptor activity. The Kyoto encyclopedia of genes and genomes (KEGG) pathway was enriched in oxidative phosphorylation, glutathione metabolism and cell cycle. ALA was found to have multiple benefits for rats after SCI, including increasing their antioxidant capacity and reducing H2 O2 levels. Additionally, it was effective in improving motor function (such as 7 days after SCI, the BBB score for SCI_ALA was 8.400 ± 0.937 compared to 7.050 ± 1.141 for SCI_Veh) and promoting histological recovery after SCI (The results of HE demonstrated that the percentage of damage area in was 44.002 ± 6.680 in the SCI_ALA and 57.215 ± 3.964 in the SCI_Veh at the center of injury.). The sequence data from this study has been deposited into Sequence Read Archive (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242507)., Conclusion: Overall, the findings of this study confirmed the beneficial effects of ALA on recovery in SCI rats through transcriptome sequencing, behavioral, as well histology analyses.- Published
- 2024
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38. The polarization of microglia and infiltrated macrophages in the injured mice spinal cords: a dynamic analysis.
- Author
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Li JL, Fu GQ, Wang YY, Bian MM, Xu YM, Zhang L, Chen YQ, Zhang N, Ding SQ, Wang R, Fang R, Tang J, Hu JG, and Lü HZ
- Subjects
- Female, Mice, Animals, Mice, Inbred C57BL, Macrophages pathology, Microglia pathology, Spinal Cord Injuries pathology
- Abstract
Background: Following spinal cord injury (SCI), a large number of peripheral monocytes infiltrate into the lesion area and differentiate into macrophages (Mø). These monocyte-derived Mø are very difficult to distinguish from the local activated microglia (MG). Therefore, the term Mø/MG are often used to define the infiltrated Mø and/or activated MG. It has been recognized that pro-inflammatory M1-type Mø/MG play "bad" roles in the SCI pathology. Our recent research showed that local M1 cells are mainly CD45
-/low CD68+ CD11b+ in the subacute stage of SCI. Thus, we speculated that the M1 cells in injured spinal cords mainly derived from MG rather than infiltrating Mø. So far, their dynamics following SCI are not yet entirely clear., Methods: Female C57BL/6 mice were used to establish SCI model, using an Infinite Horizon impactor with a 1.3 mm diameter rod and a 50 Kdynes force. Sham-operated (sham) mice only underwent laminectomy without contusion. Flow cytometry and immunohistofluorescence were combined to analyze the dynamic changes of polarized Mø and MG in the acute (1 day), subacute (3, 7 and 14 days) and chronic (21 and 28 days) phases of SCI., Results: The total Mø/MG gradually increased and peaked at 7 days post-injury (dpi), and maintained at high levels 14, 21 and 28 dpi. Most of the Mø/MG were activated, and the Mø increased significantly at 1 and 3 dpi. However, with the pathological process, activated MG increased nearly to 90% at 7, 14, 21 and 28 dpi. Both M1 and M2 Mø were increased significantly at 1 and 3 dpi. However, they decreased to very low levels from 7 to 28 dpi. On the contrary, the M2-type MG decreased significantly following SCI and maintained at a low level during the pathological process., Competing Interests: The authors declare that they have no competing interests., (© 2023 Li et al.)- Published
- 2023
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39. VX-765 reduces neuroinflammation after spinal cord injury in mice.
- Author
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Chen J, Chen YQ, Shi YJ, Ding SQ, Shen L, Wang R, Wang QY, Zha C, Ding H, Hu JG, and Lü HZ
- Abstract
Inflammation is a major cause of neuronal injury after spinal cord injury. We hypothesized that inhibiting caspase-1 activation may reduce neuroinflammation after spinal cord injury, thus producing a protective effect in the injured spinal cord. A mouse model of T9 contusive spinal cord injury was established using an Infinite Horizon Impactor, and VX-765, a selective inhibitor of caspase-1, was administered for 7 successive days after spinal cord injury. The results showed that: (1) VX-765 inhibited spinal cord injury-induced caspase-1 activation and interleukin-1β and interleukin-18 secretion. (2) After spinal cord injury, an increase in M1 cells mainly came from local microglia rather than infiltrating macrophages. (3) Pro-inflammatory Th1Th17 cells were predominant in the Th subsets. VX-765 suppressed total macrophage infiltration, M1 macrophages/microglia, Th1 and Th1Th17 subset differentiation, and cytotoxic T cells activation; increased M2 microglia; and promoted Th2 and Treg differentiation. (4) VX-765 reduced the fibrotic area, promoted white matter myelination, alleviated motor neuron injury, and improved functional recovery. These findings suggest that VX-765 can reduce neuroinflammation and improve nerve function recovery after spinal cord injury by inhibiting caspase-1/interleukin-1β/interleukin-18. This may be a potential strategy for treating spinal cord injury. This study was approved by the Animal Care Ethics Committee of Bengbu Medical College (approval No. 2017-037) on February 23, 2017., Competing Interests: None
- Published
- 2021
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- View/download PDF
40. A transcriptomic study of probenecid on injured spinal cords in mice.
- Author
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Zhang YX, Wang SN, Chen J, Hu JG, and Lü HZ
- Abstract
Background: Recent studies have found that probenecid has neuroprotective and reparative effects on central nervous system injuries. However, its effect on genome-wide transcription in acute spinal cord injury (SCI) remains unknown. In the present study, RNA sequencing (RNA-Seq) is used to analyze the effect of probenecid on the local expression of gene transcription 8 h after spinal injury., Methods: An Infinite Horizon impactor was used to perform contusive SCI in mice. The SCI model was made by using a rod (1.3 mm diameter) with a force of 50 Kdynes. Sham-operated mice only received a laminectomy without contusive injury. The injured mice were randomly assigned into either the control (SCI_C) or probenecid injection (SCI_P) group. In the latter group, the probenecid drug was intraperitoneally injected (0.5 mg/kg) immediately following injury. Eight hours after the injury or laminectomy, the spinal cords were removed from the mice in both groups. The total RNAs were extracted and purified for library preparation and transcriptome sequencing. Differential gene expressions (DEGs) of the three groups-sham, SCI_C and SCI_P-were analyzed using a DESeq software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs were performed using a GOseq R package and KOBAS software. Real-time quantitative reverse-transcriptase polymerase chain reaction was used to validate RNA-Seq results., Results: RNA-Seq showed that, compared to the SCI_C group, the number of DEGs was 641 in the SCI_P group (286 upregulated and 355 downregulated). According to GO analysis, DEGs were most enriched in extracellular matrix (ECM), collagen trimer, protein bounding and sequence specific DNA binding. KEGG analysis showed that the most enriched pathways included: cell adhesion molecules, Leukocyte transendothelial migration, ECM-receptor interactions, PI3K-Akt signaling pathways, hematopoietic cell lineages, focal adhesions, the Rap1 signaling pathway, etc. The sequence data have been deposited into the Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra/PRJNA554464)., Competing Interests: The authors declare that they have no competing interests., (© 2020 Zhang et al.)
- Published
- 2020
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41. Neuroprotective effects of P7C3 against spinal cord injury in rats.
- Author
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Duan FX, Shi YJ, Chen J, Ding SQ, Wang FC, Tang J, Wang R, Shen L, Xi J, Qi Q, Lü HZ, and Hu JG
- Subjects
- Animals, Female, Motor Activity drug effects, NAD metabolism, Neurons drug effects, Oligodendroglia drug effects, Rats, Rats, Sprague-Dawley, Spinal Cord drug effects, Spinal Cord metabolism, Carbazoles therapeutic use, Neuroprotective Agents therapeutic use, Spinal Cord Injuries drug therapy
- Published
- 2019
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- View/download PDF
42. Identification of serum exosomal microRNAs in acute spinal cord injured rats.
- Author
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Ding SQ, Chen J, Wang SN, Duan FX, Chen YQ, Shi YJ, Hu JG, and Lü HZ
- Subjects
- Acute Disease, Animals, Down-Regulation genetics, Exosomes ultrastructure, Female, Gene Expression Profiling, Gene Ontology, MicroRNAs genetics, RNA, Untranslated genetics, RNA, Untranslated metabolism, Rats, Sprague-Dawley, Reproducibility of Results, Spinal Cord pathology, Up-Regulation genetics, Exosomes metabolism, MicroRNAs blood, Spinal Cord Injuries blood, Spinal Cord Injuries genetics
- Published
- 2019
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- View/download PDF
43. Expression and localization of absent in melanoma 2 in the injured spinal cord.
- Author
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Wang SN, Guo XY, Tang J, Ding SQ, Shen L, Wang R, Ma SF, Hu JG, and Lü HZ
- Abstract
In traumatic brain injury, absent in melanoma 2 (AIM2) has been demonstrated to be involved in pyroptotic neuronal cell death. Although the pathophysiological mechanism of spinal cord injury is similar to that of brain injury, the expression and cellular localization of AIM2 after spinal cord injury is still not very clear. In the present study, we used a rat model of T9 spinal cord contusive injury, produced using the weight drop method. The rats were randomly divided into 1-hour, 6-hour, 1-day, 3-day and 6-day (post-injury time points) groups. Sham-operated rats only received laminectomy at T9 without contusive injury. Western blot assay revealed that the expression levels of AIM2 were not significantly different among the 1-hour, 6-hour and 1-day groups. The expression levels of AIM2 were markedly higher in the 1-hour, 6-hour and 1-day groups compared with the sham, 3-day and 7-day groups. Double immunofluorescence staining demonstrated that AIM2 was expressed by NeuN
+ (neurons), GFAP+ (astrocytes), CNPase+ (oligodendrocytes) and CD11b+ (microglia) cells in the sham-operated spinal cord. In rats with spinal cord injury, AIM2 was also found in CD45+ (leukocytes) and CD68+ (activated microglia/macrophages) cells in the spinal cord at all time points. These findings indicate that AIM2 is mainly expressed in neurons, astrocytes, microglia and oligodendrocytes in the normal spinal cord, and that after spinal cord injury, its expression increases because of the infiltration of leukocytes and the activation of astrocytes and microglia/macrophages., Competing Interests: None- Published
- 2019
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44. Temporal kinetics of CD8 + CD28 + and CD8 + CD28 - T lymphocytes in the injured rat spinal cord.
- Author
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Wu Y, Lin YH, Shi LL, Yao ZF, Xie XM, Jiang ZS, Tang J, Hu JG, and Lü HZ
- Subjects
- Analysis of Variance, Animals, Annexin A5 metabolism, Apoptosis physiology, Disease Models, Animal, Female, Flow Cytometry, Kinetics, Necrosis etiology, Rats, Rats, Sprague-Dawley, Spinal Cord Injuries complications, Spinal Cord Injuries immunology, Time Factors, CD28 Antigens metabolism, CD8 Antigens metabolism, Spinal Cord Injuries pathology, T-Lymphocytes physiology
- Abstract
This study aims to explore the temporal changes of cytotoxic CD8
+ CD28+ and regulatory CD8+ CD28- T-cell subsets in the lesion microenvironment after spinal cord injury (SCI) in rats, by combination of immunohistochemistry (IHC) and flow cytometry (FCM). In the sham-opened spinal cord, few CD8+ T cells were found. After SCI, the CD8+ T cells were detected at one day post-injury (dpi), then markedly increased and were significantly higher at 3, 7, and 14 dpi compared with one dpi (p < 0.01), the highest being seven dpi. In CD8+ T cells, more than 90% were CD28+ , and there were only small part of CD28- ( < 10%). After 14 days, the infiltrated CD8+ T cells were significantly decreased, and few could be found in good condition at 21 and 28 dpi. Annexin V and propidium iodide (PI) staining showed that the percentages of apoptotic/necrotic CD8+ cells at 14 dpi and 21 dpi were significantly higher than those of the other early time-points (p < 0.01). These results indicate that CD8+ T cells could rapidly infiltrate into the injured spinal cords and survive two weeks, however, cytotoxic CD8+ T cells were dominant. Therefore, two weeks after injury might be the "time window" for treating SCI by prolonging survival times and increasing the fraction of CD8+ regulatory T-cells. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)- Published
- 2017
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45. Transplantation of PDGF-AA-Overexpressing Oligodendrocyte Precursor Cells Promotes Recovery in Rat Following Spinal Cord Injury.
- Author
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Yao ZF, Wang Y, Lin YH, Wu Y, Zhu AY, Wang R, Shen L, Xi J, Qi Q, Jiang ZQ, Lü HZ, and Hu JG
- Abstract
Our previous study showed that Schwann cells (SCs) promote survival, proliferation and migration of co-transplanted oligodendrocyte progenitor cells (OPCs) and neurological recovery in rats with spinal cord injury (SCI). A subsequent in vitro study confirmed that SCs modulated OPC proliferation and migration by secreting platelet-derived growth factor (PDGF)-AA and fibroblast growth factor-2 (FGF)-2. We also found that PDGF-AA stimulated OPC proliferation and their differentiation into oligodendrocytes (OLs) at later stages. We therefore speculated that PDGF-AA administration can exert the same effect as SC co-transplantation in SCI repair. To test this hypothesis, in this study we investigated the effect of transplanting PDGF-AA-overexpressing OPCs in a rat model of SCI. We found that PDGF-AA overexpression in OPCs promoted their survival, proliferation, and migration and differentiation into OLs in vivo . OPCs overexpressing PDGF-AA were also associated with increased myelination and tissue repair after SCI, leading to the recovery of neurological function. These results indicate that PDGF-AA-overexpressing OPCs may be an effective treatment for SCI.
- Published
- 2017
- Full Text
- View/download PDF
46. Morroniside protects SK-N-SH human neuroblastoma cells against H2O2-induced damage.
- Author
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Zhang JX, Wang R, Xi J, Shen L, Zhu AY, Qi Q, Wang QY, Zhang LJ, Wang FC, Lü HZ, and Hu JG
- Subjects
- Apoptosis drug effects, Apoptosis Regulatory Proteins genetics, Apoptosis Regulatory Proteins metabolism, Caspase 3 metabolism, Cell Line, Tumor, Cell Survival drug effects, Glycosides chemistry, Humans, Lipid Peroxidation drug effects, Matrix Metalloproteinases metabolism, Membrane Potential, Mitochondrial drug effects, Neuroprotective Agents chemistry, Oxidants metabolism, Reactive Oxygen Species metabolism, Superoxide Dismutase metabolism, Glycosides pharmacology, Hydrogen Peroxide pharmacology, Neuroblastoma metabolism, Neuroprotective Agents pharmacology, Oxidative Stress drug effects
- Abstract
Oxidative stress-induced cell injury has been linked to the pathogenesis of neurodegenerative disorders such as spinal cord injury, Parkinson's disease, and multiple sclerosis. Morroniside is an antioxidant derived from the Chinese herb Shan-Zhu-Yu. The present study investigated the neuroprotective effect of morroniside against hydrogen peroxide (H2O2)-induced cell death in SK-N-SH human neuroblastoma cells. H2O2 increased cell apoptosis, as determined by flow cytometry and Hoechst 33342 staining. This effect was reversed by pretreatment with morroniside at concentrations of 1-100 µM. The increase in intracellular reactive oxygen species (ROS) generation and lipid peroxidation induced by H2O2 was also abrogated by morroniside. H2O2 induced a reduction in mitochondrial membrane potential, increased caspase-3 activity, and caused downregulation of B cell lymphoma-2 (Bcl-2) and upregulation of Bcl-2-associated X protein (Bax) expression. These effects were blocked by morroniside pretreatment. Thus, morroniside protects human neuroblastoma cells against oxidative damage by inhibiting ROS production while suppressing Bax and stimulating Bcl-2 expression, thereby blocking mitochondrial-mediated apoptosis. These results indicate that morroniside has therapeutic potential for the prevention and treatment of neurodegenerative diseases.
- Published
- 2017
- Full Text
- View/download PDF
47. Transcriptome profile of rat genes in injured spinal cord at different stages by RNA-sequencing.
- Author
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Shi LL, Zhang N, Xie XM, Chen YJ, Wang R, Shen L, Zhou JS, Hu JG, and Lü HZ
- Subjects
- Animals, Female, Gene Ontology, Rats, Rats, Sprague-Dawley, Gene Expression Profiling, Sequence Analysis, RNA, Spinal Cord Injuries genetics
- Abstract
Background: Spinal cord injury (SCI) results in fatal damage and currently has no effective treatment. The pathological mechanisms of SCI remain unclear. In this study, genome-wide transcriptional profiling of spinal cord samples from injured rats at different time points after SCI was performed by RNA-Sequencing (RNA-Seq). The transcriptomes were systematically characterized to identify the critical genes and pathways that are involved in SCI pathology., Results: RNA-Seq results were obtained from total RNA harvested from the spinal cords of sham control rats and rats in the acute, subacute, and chronic phases of SCI (1 day, 6 days and 28 days after injury, respectively; n = 3 in every group). Compared with the sham-control group, the number of differentially expressed genes was 1797 in the acute phase (1223 upregulated and 574 downregulated), 6590 in the subacute phase (3460 upregulated and 3130 downregulated), and 3499 in the chronic phase (1866 upregulated and 1633 downregulated), with an adjusted P-value <0.05 by DESeq. Gene ontology (GO) enrichment analysis showed that differentially expressed genes were most enriched in immune response, MHC protein complex, antigen processing and presentation, translation-related genes, structural constituent of ribosome, ion gated channel activity, small GTPase mediated signal transduction and cytokine and/or chemokine activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most enriched pathways included ribosome, antigen processing and presentation, retrograde endocannabinoid signaling, axon guidance, dopaminergic synapses, glutamatergic synapses, GABAergic synapses, TNF, HIF-1, Toll-like receptor, NF-kappa B, NOD-like receptor, cAMP, calcium, oxytocin, Rap1, B cell receptor and chemokine signaling pathway., Conclusions: This study has not only characterized changes in global gene expression through various stages of SCI progression in rats, but has also systematically identified the critical genes and signaling pathways in SCI pathology. These results will expand our understanding of the complex molecular mechanisms involved in SCI and provide a foundation for future studies of spinal cord tissue damage and repair. The sequence data from this study have been deposited into Sequence Read Archive ( http://www.ncbi.nlm.nih.gov/sra ; accession number PRJNA318311).
- Published
- 2017
- Full Text
- View/download PDF
48. PDGF-AA and bFGF mediate B104CM-induced proliferation of oligodendrocyte precursor cells.
- Author
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Hu JG, Wu XJ, Feng YF, Xi GM, Wang ZH, Zhou JS, and Lü HZ
- Subjects
- Animals, Cell Line, Cell Shape, Culture Media, Conditioned chemistry, Culture Media, Conditioned pharmacology, Female, Fibroblast Growth Factor 2 genetics, Fibroblast Growth Factor 2 metabolism, Gene Expression, Glial Fibrillary Acidic Protein metabolism, Insulin-Like Growth Factor I genetics, Insulin-Like Growth Factor I metabolism, Mice, Neural Stem Cells physiology, Oligodendroglia metabolism, Platelet-Derived Growth Factor genetics, Platelet-Derived Growth Factor metabolism, Rats, Rats, Sprague-Dawley, Receptor, Fibroblast Growth Factor, Type 2 metabolism, Receptor, IGF Type 1 metabolism, Receptors, Platelet-Derived Growth Factor metabolism, Cell Proliferation, Fibroblast Growth Factor 2 physiology, Oligodendroglia physiology, Platelet-Derived Growth Factor physiology
- Abstract
The conditioned medium from B104 neuroblastoma cells (B104CM) induces proliferation of οligodendrocyte precursor cells (OPCs) in vitro, which indicates that certain factors contained within B104CM give instructional signals that direct the proliferation of OPCs. However, the OPC-proliferative factors present in B104CM have yet to be identified. Platelet-derived growth factor AA (PDGF-AA), basic fibroblast growth factor (bFGF) and insulin-like growth factor-1 (IGF-1) have been reported to act as potent mitogens for OPC proliferation. This raises the possibility that B104CM induces proliferation of OPCs through secretion of PDGF‑AA, bFGF and/or IGF-1. In the present study, we detected the expression and levels of PDGF-AA, bFGF and IGF-1 in B104 cells and B104CM, and observed the expression of their receptors in OPCs. The results indicated that these growth factors were expressed in B104 cells and B104CM. All 3 receptors, PDGFR, FGFR2 and IGF-1R, were also detected in OPCs. Furthermore, B104CM-stimulated OPC proliferation could be markedly decreased by both AG1295 (an inhibitor of PDGFR) and PD173074 (an inhibitor of FGFR). However, the inhibition of IGF-1R with AG1204 did not affect the proliferation of OPCs. Our study suggests that the PDGF-AA and bFGF in B104CM are 2 key factors that stimulate OPC proliferation.
- Published
- 2012
- Full Text
- View/download PDF
49. Formation and aggregation of lipid rafts in γδ T cells following stimulation with Mycobacterium tuberculosis antigens.
- Author
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Lü HZ, Zhu AY, Chen Y, Tang J, and Li BQ
- Subjects
- Adult, Cell Separation, Flow Cytometry methods, Fluorescein-5-isothiocyanate, G(M1) Ganglioside biosynthesis, Humans, Lymphocyte Activation immunology, Microscopy, Confocal methods, Time Factors, beta-Cyclodextrins, Antigens, Bacterial immunology, Membrane Microdomains chemistry, Mycobacterium tuberculosis immunology, Receptors, Antigen, T-Cell, gamma-delta immunology
- Abstract
Lipid rafts are plasma membrane microdomains that are implicated in diverse signaling pathways in immune cells. Based on the distinct types of T-cell receptors, two T-cell subpopulations have been identified: αβ and γδ T cells. In humans, γδ T cells represent a relatively rare T lymphocyte population but play a critical role in the immune response to infection by Mycobacterium tuberculosis. It has been demonstrated that Mycobacterium tuberculosis antigens (Mtb-Ag) preferentially activate γδ T cells. Thus, we investigated whether lipid rafts are involved in the Mtb-Ag-mediated activation of γδ T cells. Human peripheral blood mononuclear cells (PBMCs) were stimulated with Mtb-Ag, and expression of a lipid raft marker ganglioside GM1 (GM1) was determined by flow cytometry. The aggregation of lipid rafts was evaluated by laser confocal microscopy. Non-stimulated fresh PBMCs minimally expressed GM1 (6.55 ± 2.01%) and had no aggregated rafts in γδ T cells. Mtb-Ag stimulation gradually increased the expression of GM1 in a time-dependent manner. At 72 h, the majority of γδ T cells expressed GM1 (88.69 ± 7.55%). Furthermore, accompanied with the increased expression of GM1, aggregation of lipid rafts became gradually visible in γδ T cells. The aggregated rafts, however, were not evenly distributed and only occurred over a small portion of GM1-positive cells. Pretreatment with methyl-β-cyclodextrin, a cholesterol-depleting reagent, completely inhibited the Mtb-Ag-mediated aggregation of lipid rafts. These results demonstrate that lipid raft aggregation occurs in Mtb-Ag-activated γδ T cells, suggesting that lipid rafts are involved in activation of γδ T cells.
- Published
- 2011
- Full Text
- View/download PDF
50. Differential gene expression in oligodendrocyte progenitor cells, oligodendrocytes and type II astrocytes.
- Author
-
Hu JG, Wang YX, Zhou JS, Chen CJ, Wang FC, Li XW, and Lü HZ
- Subjects
- Animals, Cell Differentiation, DNA, Complementary genetics, Gene Expression Profiling, Immunohistochemistry methods, Nucleic Acid Hybridization, Oligonucleotide Array Sequence Analysis, Rats, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Astrocytes cytology, Gene Expression Regulation, Developmental, Oligodendroglia cytology, Stem Cells cytology
- Abstract
Oligodendrocyte precursor cells (OPCs) are bipotential progenitor cells that can differentiate into myelin-forming oligodendrocytes or functionally undetermined type II astrocytes. Transplantation of OPCs is an attractive therapy for demyelinating diseases. However, due to their bipotential differentiation potential, the majority of OPCs differentiate into astrocytes at transplanted sites. It is therefore important to understand the molecular mechanisms that regulate the transition from OPCs to oligodendrocytes or astrocytes. In this study, we isolated OPCs from the spinal cords of rat embryos (16 days old) and induced them to differentiate into oligodendrocytes or type II astrocytes in the absence or presence of 10% fetal bovine serum, respectively. RNAs were extracted from each cell population and hybridized to GeneChip with 28,700 rat genes. Using the criterion of fold change > 4 in the expression level, we identified 83 genes that were up-regulated and 89 genes that were down-regulated in oligodendrocytes, and 92 genes that were up-regulated and 86 that were down-regulated in type II astrocytes compared with OPCs. The up-regulated genes, such as activating transcription factor 3 and myelin basic protein in oligodendrocytes or claudin 11 in type II astrocytes, might contribute to OPC differentiation and represent constitutive components of oligodendrocytes or type II astrocytes. The down-regulated genes in both oligodendrocytes and type II astrocytes, such as transcription factor 19, might be involved in maintaining self-renewal and/or represent the property of OPCs. These results provide new insights into the elucidation of the molecular mechanisms, by which OPCs differentiate to oligodendrocytes or type II astrocytes.
- Published
- 2011
- Full Text
- View/download PDF
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