Toxicology Research
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2025
·Vol. 14
·期 2
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IF 2.1
Fu Dan,Li Ziyou,Feng Huafeng,Fan Fangling,Zhang Wang,He Liang
Spinal cord injury (SCI)-induced ischemic delayed paralysis is one of the most serious side effects of aneurysms surgeries. Recent studies prove that the activation of autophagy, including macroautophagy and micro-autophagy pathways, occur during SCI-induced brain neuron damage. However, the role of chaperone mediated autophagy (CMA) during SCI remains to be unveiled. In the present work, rat model of delayed paralysis after aneurysms operation and adenovrius induced LAMP2A knockdown in microglia cells were applied in the present work to investigate the involvement of LAMP2A-mediated CMA in the aneurysm operation related SCI and delayed paralysis. The results showed that LAMP2A was upregulated in the SCI procedure, and contributed to neuron death and pro-inflammation perturbation via inducing iNOS+ polarization in microgila. We additionally observed that knockdown of LAMP2A resulted in the shift of microglia from iNOS+ to ARG1+ phenotype, as well as alleviated neuron damage during SCI. Furthermore, the analysis of BBB score, the result of immunohistological staining, and protein detection confirmed the activation of LAMP2A-mediated CMA activation and its interaction with NF-κB signaling, which leads to neuron death and motor function loss. These results prove that LAMP2A-mediated CMA contributes to the upregulation of pro-inflammatory cytokines and results in cell death in neurons during ischemic delayed paralysis via activating NF-κB signaling. Inhibition of LAMP2A promotes neurons survival during ischemic delayed paralysis.
研究领域:
神经科学
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分子生物学
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医学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Xiaobang Liu,Jiaqun Du,Junpeng Sun,Han Wang,Jinyu An,Yingqiao Li,Yu Hu,Shuai Cheng,Huicong Feng,He Tian,Xifan Mei,Yang Qiu,Chao Wu
Spinal cord injury (SCI) is a serious neurological disease that can result in paralysis. After SCI occurs, the blood–spinal cord barrier (BSCB) is disrupted, and permeability is transiently elevated. However, the permeability of the BSCB returns to normal over time, which prevents many drugs from being used in subsequent treatments. In this study, we designed a borneol-functionalized macrophage membrane encapsulating mesoporous selenium nanoparticles loaded with resveratrol (MSe-Res-BMMs) for SCI treatment. In vivo animal experiments and in vitro cell experiments demonstrated that MSe-Res-BMMs were able to protect neurons from ferroptosis by reducing ROS levels and increasing glutathione peroxidase-4 (GPx-4) activity. In addition, this treatment also reduced ROS-induced inflammation and apoptosis by decreasing the expression of inflammatory factor IL-1β and apoptotic factor Cleaved Caspase-3 at the site of injury. Therefore, MSe-Res-BMMs are expected to provide new therapeutic options for SCI treatment.
研究领域:
神经科学
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药理学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Chen Tianjun,Wan Li,Xiao Yongchun,Wang Ke,Wu Ping,Li Can,Huang Caiqiang,Liu Xiangge,Xue Wei,Sun Guodong,Ji Xin,Lin Hongsheng,Ji Zhisheng
Spinal cord injury (SCI) often accompanies impairment of motor function, yet there is currently no highly effective treatment method specifically for this condition. Oxidative stress and inflammation are pivotal factors contributing to severe neurological deficits after SCI. In this study, a type of curcumin (Cur) nanoparticle (HA-CurNPs) was developed to address this challenge by alleviating oxidative stress and inflammation. Through non-covalent interactions, curcumin (Cur) and poly (-)-epigallocatechin-3-gallate (pEGCG) are co-encapsulated within hyaluronic acid (HA), resulting in nanoparticles termed HA-CurNPs. These nanoparticles gradually release curcumin and pEGCG at the SCI site. The released pEGCG and curcumin not only scavenge reactive oxygen species (ROS) and prevents apoptosis, thereby improving the neuronal microenvironment, but also regulate CD74 to promote microglial polarization toward an M2 phenotype, and inhibits M1 polarization, thereby suppressing the inflammatory response and fostering neuronal regeneration. Moreover, in vivo experiments on SCI mice demonstrate that HA-CurNPs effectively protect neuronal cells and myelin, reduce glial scar formation, thereby facilitating the repair of damaged spinal cord tissues, restoring electrical signaling at the injury site, and improving motor functions. Overall, this study demonstrates that HA-CurNPs significantly reduce oxidative stress and inflammation following SCI, markedly improving motor function in SCI mice. This provides a promising therapeutic approach for the treatment of SCI.
研究领域:
神经科学
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药理学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Bio-Design and Manufacturing
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2024
·
IF 8.1
Xu Tao,Yang Changwei,Lu Yang,Wang Heng,Chen Cheng,Zhou Yuchen,Chen Xiaoqing
The recovery and reconstruction of central nervous system function after spinal cord injury (SCI) is a worldwide problem. The difficulty lies in the feasibility issue of new axons passing through the injured area and the negative effect of scarring after injury. As a biological material, the human amniotic membrane (HAM) has the advantages of protecting nerve growth, inhibiting scar formation, and promoting neovascularization, but its weak physical properties are difficult to apply in treating SCI. In this study, HAMs were first decellularized and then chemically grafted with methacrylic anhydride. Next, the composite was photocrosslinked with gelatin methacrylate to prepare a cross-network biological complex. The final complexes prepared by appeal were used for in vitro and in vivo studies of SCI in rats, separately. In the in vitro experiment, the composite scaffold inherited abundant biological factors from the amniotic membrane and had the physical properties of a hydrogel, thus providing a favorable environment for the growth and development of neurons and blood vessels. In the in vivo experiment, the composite reduced scarring and promoted the growth of new nerves. Overall, the composite scaffolds can stably simulate the extracellular microenvironment in SCI defects, regulate pathological changes, and promote the generation of new neurons. Therefore, decellularized HAM hydrogels are promising biocomposite materials for central nerve repair after SCI. Graphic abstract
研究领域:
生物材料学
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神经科学
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再生医学
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产品关联
DOI
高影响因子
PROGRESS IN ORGANIC COATINGS
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2024
·
IF 6.5
Shicun Jin,Jinfeng Cao,Kuang Li,Jianzhang Li,Huining Xiao,Ping Wu
Hydrogels can simulate the physiological environment of soft tissues, showing great promise in spinal cord injury (SCI) repair. Nevertheless, hydrogels for effective SCI repair have limitations such as their inability to effectively contact with irregular cavities and structural damage caused by long-term physical movement. In this study, a unique and facile hydrogel with injectable, electroconductive, self-healing, and adhesive properties was synthesized by introducing tannic acid (TA) and polyvinylpyrrolidone (PVP)-stabilized polypyrrole (PPy) nanoparticles. Fe(III) ion-triggered in situ polymerization of pyrrole, and the dispersibility of PPy was significantly improved utilizing the stabilizing effect of PVP. The P@Py/TA had excellent injectable, self-healing, and cytocompatibility properties. Meanwhile, the hydrogel coating exhibited robust self-adhesion to different substrates. The P@Py/TA provided a suitable microenvironment for axon regeneration, effective angiogenesis, and immune-regulated function. This facilitated functional recovery from traumatic SCI. The multifunctional conductive P@Py/TA hydrogel scaffold provides a new strategy for SCI repair and has potential applications in other fields of bionic skin and multi-functional coatings.
研究领域:
生物材料学
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组织工程学
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神经科学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Penghui Fan,Shangzhi Li,Junfeng Yang,Kaidan Yang,Ping Wu,Qi Dong,Yingshan Zhou
The cystic cavity that develops following spinal cord injury is a major obstacle for repairing spinal cord injury (SCI). The injectable self-healing biomaterials treatment is a promising strategy to enhance tissue repair after traumatic spinal cord injury. Herein, a natural extracellular matrix (ECM) biopolymer hyaluronic acid-based hydrogel was developed based on multiple dynamic covalent bonds. The hydrogels exhibited excellent injectable and self-healing properties, could be effectively injected into the injury site, and filled the lesion cavity to accelerate the tissue repair of traumatic SCI. Moreover, the hydrogels were compatible with cells and various tissues and possessed proper stiffness matched with nervous tissue. Additionally, when implanted into the injured spinal cord site, the hyaluronic acid-based hydrogel promoted axonal regeneration and functional recovery by accelerating remyelination, axon regeneration, and angiogenesis. Overall, the injectable self-healing hyaluronic acid-based hydrogels are ideal biomaterials for treating traumatic SCI.
研究领域:
生物材料学
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神经科学
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组织工程学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
·
2018
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IF 2.159
Dongling Shi,Teng He,Weijian Tang,Heyangzi Li,Chao Wang,Mingzhi Zheng,Jue Hu,Xinghui Song,Yuemin Ding,Ying-ying Chen,Yueliang Shen,Hongfeng Jin,Lin-lin Wang
Neuronal death and organization degeneration can happen inordinately after spinal cord injury (SCI), which lead to nerve dysfunction. We aimed to determine whether local application of a cell permeable calpain I inhibitor (MDL28170) can promote SCI recovery by increasing neuronal cell viability. MDL28170-loaded polycaprolactone (PCL) film was fabricated. Scanning electron microscopy showed the surface of PCL film was smooth with holes (diameter at μM level). The PCL film was non-toxic, biological compatibility, and had good neuron adhension and slow release characteristic. MDL28170 increased VSC4.1 motor neurons’ viability under tunicamycin (an endoplasmic reticulum stress) induced injury. In a traumatic SCI rat model, MDL28170-loaded PCL film reduced the area of lesion cavity, and promoted recovery of locomotor behavior. Moreover, the expression of GAP-43 was upregulated after MDL28170-loaded PCL film treatment. Thus, our findings demonstrated that localized delivery of MDL28170 could promote SCI recovery by inhibiting endoplasmic reticulum stress, preserving survival of the motor neurons, which may point out a promising therapeutic target for treating SCI patient.
研究领域:
神经科学
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生物医学工程
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Genome Medicine
·
2025
·Vol. 17
·期 1
·1-25
·
IF 11.2
Zhou Ren,Chen Jibao,Tang Yunhan,Wei Chuijin,Yu Ping,Ding Xinmei,Zhu Li’ao,Yao Jiajia,Ouyang Zengqiang,Qiao Jing,Xiong Shumin,Dong Liaoliao,Yin Tong,Li Haiqing,Feng Ye,Cheng Lin
Background Exercise rehabilitation therapy has garnered widespread recognition for its beneficial effects on the restoration of locomotor function in individuals with spinal cord injury (SCI). Notably, resistance exercise has demonstrated significant improvements in muscle strength, coordination, and overall functional recovery. However, to optimize clinical management and mimic exercise-like effects, it is imperative to obtain a comprehensive understanding of the molecular alterations that underlie these positive effects. Methods We conducted a randomized controlled clinical trial investigating the effects of resistance exercise therapy for incomplete SCI. We integrated the analysis of plasma proteomics and peripheral blood mononuclear cells (PBMC) transcriptomics to explore the molecular and cellular changes induced by resistance exercise. Subsequently, we established a weight-loaded ladder-climbing mouse model to mimic the physiological effects of resistance exercise, and we analyzed the plasma proteome and metabolome, as well as the transcriptomes of PBMC and muscle tissue. Lastly, to confirm the transmissibility of the neuroprotective effects induced by resistance exercise, we intravenously injected plasma obtained from exercised male mice into SCI female mice during the non-acute phase. Results Plasma proteomic and PBMC transcriptomic profiling underscored the notable involvement of the complement pathways and humoral immune response in the process of restoring locomotor function following SCI in the human trial. Moreover, it was emphasized that resistance exercise interventions could effectively modulate these pathways. Through employing plasma proteomic profiling and transcriptomic profiling of PBMC and muscle tissues in mice, our study revealed immunomodulatory responses that parallel those observed in human trials. In addition, our analysis of plasma metabolomics revealed an enhancement in lipid metabolism following resistance exercise. We observed that resistance exercise plasma exhibited significant effects in ameliorating locomotor disability after SCI via reducing demyelination and inhibiting neuronal apoptosis. Conclusions Our investigation elucidates the molecular alterations associated with resistance exercise therapy promoting recovery of locomotor function following incomplete SCI. Moreover, we demonstrate the direct neuroprotective effects delivered via exercise plasma injection, which facilitates spinal cord repair. Mechanistically, the comprehensive multi-omics analysis involving both human and mice reveals that the principal constituents responsible for the observed neuroprotective effects within the plasma are predominantly immunoregulatory factors, warranting further experimental validation. Trial registration The study was retrospectively registered on 17 July, 2024, in Chinese Clinical Trial Registry (No.: ChiCTR2400087038) at https://www.chictr.org.cn/ .
研究领域:
医学
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神经科学
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运动康复
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Bioengineering-Basel
·
2022
·Vol. 9
·期 10
·535
·
IF 5.046
Chen Qiu,Yuan Sun,Jinying Li,Yuchen Xu,Jiayi Zhou,Cong Qiu,Shaomin Zhang,Yong He,Luyang Yu
Spinal cord injury (SCI) results in devastating consequences for the motor and sensory function of patients due to neuronal loss and disrupted neural circuits, confronting poor prognosis and lack of effective therapies. A new therapeutic strategy is urgently required. Here, human amniotic epithelial cells (hAEC), featured with immunocompatibility, non-tumorgenicity and no ethical issues, were induced into neural-like cells by a compound cocktail, as evidenced with morphological change and the expression of neural cell markers. Interestingly, the hAEC-neural-like cells maintain the characteristic of low immunogenicity as hAEC. Aiming at SCI treatment in vivo, we constructed a 3D-printed GelMA hydrogel biomimetic spinal cord scaffold with micro-channels, in which hAEC-neural-like cells were well-induced and grown. In a rat full transection SCI model, hAEC-neural-like cell scaffolds that were implanted in the lesion demonstrated significant therapeutic effects; the neural circuit and hindlimb locomotion were partly recovered compared to little affection in the SCI rats receiving an empty scaffold or a sham implantation operation. Thus, the establishment of hAEC-neural-like cell biomimetic scaffolds may provide a safe and effective treatment strategy for SCI.Keywords:human amniotic epithelial cell;neural cell;biomimetic scaffold;spinal cord injury
研究领域:
神经科学
·
组织工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 5
·573
·
IF 5.5
Yang Liu,Yingkai Wang,Xiangzi Wang,Wanchen Zeng,Zehong Zhang,Zhengmian Zhang,Zhongquan Qi
Background: Spinal cord injury (SCI) is a devastating neurological condition with limited therapeutic options. Current clinical interventions predominantly rely on prolonged or high-dose pharmacological regimens, often causing systemic toxicity and adverse events. Although black phosphorus nanosheets (BPNSs) exhibit remarkable reactive oxygen species (ROS)-scavenging capacity to mitigate oxidative damage, their rapid degradation severely compromises their therapeutic efficacy.Methods: This study presents a thermosensitive hydrogel with rapid gelation properties by incorporating different proportions and concentrations of sodium alginate (SA) into a chitosan/β-glycerophosphate (CS/β-GP) hydrogel and loading it with BPNS for the treatment of SCI in rats. In vitro, the physical properties of the composite were characterized and the cytotoxicity and ROS scavenging abilities were assessed using PC12 cells; in vivo, behavioral tests, histopathological analysis, transcriptomics, immunohistochemistry, and Western blotting were performed to explore the therapeutic effects and mechanisms.Results: The results demonstrate that this hydrogel effectively slows BPNS degradation, exhibits a high ROS scavenging capacity, reduces lipid peroxidation, and thereby inhibits ferroptosis and apoptosis, offering neuroprotective effects and promoting motor function recovery.Conclusions: Our findings establish the CS/β-GP/SA-BPNS hydrogel as a multifunctional therapeutic platform for SCI, synergizing sustained drug release with ROS–ferroptosis–apoptosis axis modulation to achieve neuroprotection and functional restoration. This strategy provides a translatable paradigm for combining nanotechnology and biomaterial engineering in neural repair.
研究领域:
神经科学
·
生物材料学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Yihan Chen,Yuanqing Ding,Min Ge,Ya-Xuan Zhu,Yanling You,Zhixin Chen,Yiming Tao,Rong Xie,Han Lin,Jianlin Shi
Spinal cord injury (SCI) refers to either a temporary or permanent damage to the spinal cord caused by external forces, which frequently leads to the acute or sustained impairment on the motor and sensory functions of spinal cord and several chronic systemic complications. Current clinical interventions fail to meet the therapeutic needs in a satisfactory way due to the limited efficacy associated with the blood-spinal cord barrier (BSCB). Here, we propose a strategy for the treatment of spinal cord injury (SCI) using a NIR photothermal-controlled release gas nano-generator based on silicene (SNS) nanosheets. This nano gas-generator greatly promotes nerve regeneration attributing to the physiological effects of H 2 S, including the inhibition on inflammation and oxidative stress, protections of nerve cells from the injury, promotion of neuron formation and reduction of glial scar formation. The results show that H 2 S-generator is capable of reducing the expressions of activated microglia macrophages and pro-inflammatory cytokines via the NF-κB pathway in SCI mice, which significantly promotes the axon regeneration and functional recovery after SCI. The sustained effectiveness of the generator in the repair of SCI offers a promising prospect in the treatments of a range of neuro-degenerations in addition to spinal cord injury, such as Parkinson's disease and Alzheimer's disease.
研究领域:
神经科学
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生物医学工程
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药理学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Xiangyu Liu,Biao Ma,Sihan Hu,Dandan Li,Chun Pan,Zhuobin Xu,Hao Chen,Yongxiang Wang,Huihui Wang
Dynamic alterations in metal ion concentrations are observed in the pathological process of spinal cord injury (SCI). Hence, strategically supplying metal ions in a phase-adapted manner is promising to facilitate injured spinal cord repair by preventing pathological damage. To achieve this, a chimeric hydrogel microsphere with Mg 2+ -crosslinked methacrylate gelatin as the "shell" and Zn 2+ -loaded poly (lactic-co-glycolic acid) (PLGA) as the "core" was designed. The chimeric microspheres allow continuous delivery of Mg 2+ or Zn 2+ at the exact required phase in SCI pathological process. Early release of Mg 2+ reduced inflammation by diminishing the secretion of proinflammatory cytokines due to changes in macrophage polarization, which further suppressed scar formation to create an ideal space for neural regeneration. The subsequently released Zn 2+ at the late phase effectively promoted neural cell proliferation and regeneration, which was accompanied by activation of mature neurons, interneurons, and motor neurons, leading to significant behavioral recovery. Thus, this study underscores the critical role of metal ions at different phases of injured spinal cord repair and describes the construction of an injectable chimeric hydrogel microsphere carrying distinct metal ions with a core-shell structure. Chimeric microspheres overcome the discrepancy between the inflammatory response and neural regeneration and are a promising therapeutic strategy for injured spinal cord repair.
研究领域:
生物材料学
·
神经科学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）