COMPOSITES PART B-ENGINEERING
·
2023
·
IF 13.1
Renliang Zhao,Yifan Shen,Xiangtian Deng,Yunfeng Tang,Zilu Ge,Dong Wang,Zhencheng Xiong,Qian Fang,Zhang Zhen,Xiaolin Li,Xiaotian Du,Wei Lin,Shichang Zhao,Guanglin Wang
The clinical indications reveal that traumatic brain injury (TBI) accelerates the process of limb bone regeneration. However, the mechanisms underlying this phenomenon remain ambiguous. In this inquiry, the activation of endogenous neural stem cells in the hippocampus post TBI led to the secretion of extracellular vesicles (NSC-EV) that targeted bone marrow mesenchymal stem cells, ultimately promoting bone healing. The enrichment of miR-9-5p in NSC-EV facilitated osteogenesis through the activation of the MAP3K3 pathway. We also present a novel hydrogel formulation for clinical application of NSC-EVs by means of ROS-responsive EV delivery. The hydrogel was cross-linked with EVs to create a water-based gel encapsulation, which was applied to a 3D-printed β-TCP scaffold for controlled long-term release that corresponded to those of physiological bone tissue. Our investigation represents the inaugural usage of EVs derived from neural stem cells in bone tissue engineering. These EVs were found to encourage information exchange between the central nervous system and bone tissue regeneration. Our composite scaffold demonstrated impressive bone regeneration qualities in rats with cranial defects, highlighting its potential for pioneering approaches in bone tissue engineering and innovative medical technologies for clinical applications.
研究领域:
再生医学
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干细胞生物学
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组织工程
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神经科学
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骨生物学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
LIFE SCIENCES
·
2025
·
IF 5.1
Kaiji Li,Jinchao Wang,Yalong Gao,Xin Chen,Ruilong Peng,Lei Li,Cong Wang,Tuo Li,Shu Zhang,Guili Yang,Jianning Zhang
Aims Traumatic brain injury-induced coagulopathy (TBI-IC) frequently occurs after TBI, exacerbating the severity of TBI and affecting patient prognosis. Benzbromarone (BBR) is commonly used to treat hyperuricemia; however, its protective effects against TBI-IC remain unknown. Therefore, we explored whether BBR could improve TBI. Materials and methods C57BL/6 wild-type mice were subjected to fluid percussion injury to mimic TBI, and BBR was administered intraperitoneally 30 min after TBI. Magnetic resonance imaging (MRI) and Evans blue dye extravasation were used to assess the prognosis, tail bleeding time, ELISA, and coagulation tests assess coagulation function. We further explored the potential mechanism by which BBR alleviates hypercoagulation after TBI using flow cytometry. Key findings The intraperitoneally injected BBR group showed improved survival and neurological severity scores compared to the TBI group. Subsequently, we found that hypercoagulability developed 3 h after TBI and that the administration of BBR improved this hypercoagulability. BBR also reduced the degree of platelet phosphatidylserine (PS) exposure after TBI, platelet activation, and Ca2+ overload, in addition to inhibition of scramblase activity in procoagulant platelets. Significance Our findings indicate that BBR reduces PS externalization by inhibiting TMEM16F expression, thereby improving blood hypercoagulability after TBI.
研究领域:
神经科学
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药理学
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血液学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2024
·
IF 3.5
Xu Ren,Yun-Fei Li,Tian-Wei Pei,Hao-Sheng Wang,Yu-Hai Wang,Tao Chen
Background Traumatic brain injury (TBI) is a leading cause of high mortality and disability worldwide. Overactivation of astrocytes and overexpression of inflammatory responses in the injured brain are characteristic pathological features of TBI. Rosiglitazone (ROS) is a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist known for its anti-inflammatory activity. However, the relationship between the inflammatory response involved in ROS treatment and astrocyte A1 polarization remains unclear. Objective This study aimed to investigate whether ROS treatment improves dysfunction and astrocyte A1 polarization induced after TBI and to elucidate the underlying mechanisms of these functions. Methods SD rats were randomly divided into sham operation group, TBI group, TBI+ROS group, and TBI+ PPAR-γ antagonist group (GW9662 + TBI). The rat TBI injury model was prepared by the CCI method; brain water content test and wire grip test scores suggested the prognosis; FJB staining showed the changes of ROS on the morphology and number of neurons in the peripheral area of cortical injury; ELISA, immunofluorescence staining, and western blotting analysis revealed the effects of ROS on inflammatory response and astrocyte activation with the degree of A1 polarization after TBI. Results Brain water content, inflammatory factor expression, and astrocyte activation in the TBI group were higher than those in the sham-operated group (P < 0.05); compared with the TBI group, the expression of the above indexes in the ROS group was significantly lower (P < 0.05). Compared with the TBI group, PPAR-γ content was significantly higher and C3 content was considerably lower in the ROS group (P < 0.05); compared with the TBI group, PPAR-γ content was significantly lower and C3 content was substantially higher in the inhibitor group (P < 0.05). Conclusion ROS can exert neuroprotective effects by inhibiting astrocyte A1 polarization through the PPAR-γ pathway based on the reduction of inflammatory factors and astrocyte activation in the brain after TBI.
研究领域:
神经科学
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药理学
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炎症
·
创伤
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Yuhan Han,Weiji Weng,Yongkang Zhang,Qiyuan Feng,Yuxiao Ma,Ankang Quan,Xianhua Fu,Xinxin Zhao,Loren Skudder-Hill,Jiyao Jiang,Yan Zhou,Honglin Chen,Junfeng Feng
In managing severe traumatic brain injury (TBI), emergency surgery involving the removal of damaged brain tissue and intracerebral hemorrhage is a priority. Secondary brain injury caused by oxidative stress and energy metabolic disorders, triggered by both primary mechanical brain damage and surgical insult, is also a determining factor in the prognosis of TBI. Unfortunately, the effectiveness of traditional postoperative intravenous neuroprotective agents therapy is often limited by the lack of targeting, timeliness, and side effects when neuroprotective agents systemically delivered. Here, we have developed injectable, intelligent, self-assembling hydrogels (P-RT/2DG) that can achieve precise treatment through intraoperative application to the target area. P-RT/2DG hydrogels were prepared by integrating a reactive oxygen species (ROS)-responsive thioketal linker (RT) into polyethylene glycol. By scavenging ROS and releasing 2-deoxyglucose (2DG) during degradation, these hydrogels functioned both in antioxidation and energy metabolism to inhibit the vicious cycle of post-TBI ROS–lactate which provoked secondary injury. In vitro and in vivo tests confirmed the absence of systemic side effects and the neuroprotective function of P-RT/2DG hydrogels in reducing edema, nerve cell apoptosis, neuroinflammation, and maintaining the blood-brain barrier. Our study thus provides a potential treatment strategy with novel hydrogels in TBI.
研究领域:
神经外科
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药理学
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生物医学工程
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Neural Regeneration Research
·
2022
·
IF 6.058
Wei Wang,Qiu-Yuan Gong,Lin Cai,Yao Jing,Dian-Xu Yang,Fang Yuan,Hao Chen,Heng-Li Tian
Sirtuin 2 (SIRT2) inhibition or Sirt2 knockout in animal models protects against the development of neurodegenerative diseases and cerebral ischemia. However, the role of SIRT2 in traumatic brain injury (TBI) remains unclear. In this study, we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema, attenuated disruption of the blood-brain barrier, decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, reduced the activity of the effector caspase-1, reduced neuroinflammation and neuronal pyroptosis, and improved neurological function. Knockout of Sirt2 in a mechanical stretch injury cell model in vitro also decreased expression of the NLRP3 inflammasome and pyroptosis. Our findings suggest that knockout of Sirt2 is neuroprotective against TBI; therefore, Sirt2 could be a novel target for TBI treatment.
研究领域:
神经科学
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分子生物学
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神经病学
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2024
·
IF 4.6
Shi Haoyu,Song Libiao,Wu Yonghui,Shen Ruonan,Zhang Chenxu,Liao Xingzhi,Wang Qiuhong,Zhu Jie
Traumatic brain injury (TBI) is a highly severe form of trauma with complex series of reactions in brain tissue which ultimately results in neuronal damage. Previous studies proved that neuronal ferroptosis, which was induced by intracranial haemorrhage and other reasons, was one of the most primary causes of neuronal damage following TBI. However, the association between neuronal mechanical injury and ferroptosis in TBI and relevant treatments remain unclear. In the present study, we first demonstrated the occurrence of neuronal ferroptosis in the early stage of TBI and preliminarily elucidated that edaravone (EDA), a cerebroprotective agent that eliminates oxygen radicals, was able to inhibit ferroptosis induced by TBI. A cell scratching model was established in PC12 cells, and it was confirmed that mechanical injury induced ferroptosis in neurons at the early stage of TBI. Ferroptosis suppressor protein 1 (FSP1) plays a significant role in inhibiting ferroptosis, and we found that iFSP, a ferroptosis agonist which is capable to inhibit FSP1 pathway, attenuated the anti-ferroptosis effect of EDA. In conclusion, our results suggested that EDA inhibited neuronal ferroptosis induced by mechanical injury in the early phase of TBI by activating FSP1 pathway, which could provide evidence for future research on prevention and treatment of TBI.
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2021
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IF 11.556
Shaofang Zhang,Ying Liu,Si Sun,Junying Wang,Qifeng Li,Ruijuan Yan,Yalong Gao,Haile Liu,Shuangjie Liu,Wenting Hao,Haitao Dai,Changlong Liu,Yuanming Sun,Wei Long,Xiaoyu Mu,Xiao-Dong Zhang
Traumatic brain injury (TBI) is a sudden injury to the brain, accompanied by the production of large amounts of reactive oxygen and nitrogen species (RONS) and acute neuroinflammation responses. Although traditional pharmacotherapy can effectively decrease the immune response of neuron cells via scavenging free radicals, it always involves in short reaction time as well as rigorous clinical trial. Therefore, a noninvasive topical treatment method that effectively eliminates free radicals still needs further investigation. Methods: In this study, a type of catalytic patch based on nanozymes with the excellent multienzyme-like activity is designed for noninvasive treatment of TBI. The enzyme-like activity, free radical scavenging ability and therapeutic efficacy of the designed catalytic patch were assessed in vitro and in vivo . The structural composition was characterized by the X-ray diffraction, X-ray photoelectron spectroscopy and high-resolution transmission electron microscopy technology. Results: Herein, the prepared Cr-doped CeO 2 (Cr/CeO 2 ) nanozyme increases the reduced Ce 3+ states, resulting in its enzyme-like activity 3-5 times higher than undoped CeO 2 . Furthermore, Cr/CeO 2 nanozyme can improve the survival rate of LPS induced neuron cells via decreasing excessive RONS. The in vivo experiments show the Cr/CeO 2 nanozyme can promote wound healing and reduce neuroinflammation of mice following brain trauma. The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases. Conclusions: The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases.
研究领域:
神经科学
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纳米技术
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药理学
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材料科学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 6
·1-15
·
IF 5.3
Wang Yupeng,Yu Zhiyong,Ning Zhenqiu,Li Minghui,Li Weiping,Zhong Yizhe,Chen Huiqiang,Zhang Xi,Tang Xialin,Cheng Xiao,Li Laiqing,Aigul Abduldayeva,Zan Jie
Glial fibrillary acidic protein (GFAP) in serum has been shown as a biomarker of traumatic brain injury (TBI) which is a significant global public health concern. Accurate and rapid detection of serum GFAP is critical for TBI diagnosis. In this study, a time-resolved fluorescence immunochromatographic test strip (TRFIS) was proposed for the quantitative detection of serum GFAP. This TRFIS possessed excellent linearity ranging from 0.05 to 2.5 ng/mL for the detection of serum GFAP and displayed good linearity ( Y = 598723 X + 797198, R 2 = 0.99), with the lowest detection limit of 16 pg/mL. This TRFIS allowed for quantitative detection of serum GFAP within 15 min and showed high specificity. The intra-batch coefficient of variation (CV) and the inter-batch CV were both < 4.0%. Additionally, this TRFIS was applied to detect GFAP in the serum samples from healthy donors and patients with cerebral hemorrhage, and the results of TRFIS could efficiently discern the patients with cerebral hemorrhage from the healthy donors. Our developed TRFIS has the characteristics of high sensitivity, high accuracy, and a wide linear range and is suitable for rapid and quantitative determination of serum GFAP on-site. Graphical abstract
研究领域:
生物医学工程
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临床化学
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神经学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2020
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IF 8.724
Yantao Zheng,Gang Wu,Limei Chen,Ying Zhang,Yuwei Luo,Yong Zheng,Fengjun Hu,Tymor Forouzanfar,Haiyan Lin,Bin Liu
Brain tissues that are severely damaged by traumatic brain injury (TBI) is hardly regenerated, which leads to a cavity or a repair with glial scarring. Stem-cell therapy is one viable option to treat TBI-caused brain tissue damage, whose use is, whereas, limited by the low survival rate and differentiation efficiency of stem cells. To approach this problem, we developed an injectable hydrogel using imidazole groups-modified gelatin methacrylate (GelMA-imid). In addition, polydopamine (PDA) nanoparticles were used as carrier for stromal-cell derived factor-1 (SDF-1α). GelMA-imid hydrogel loaded with [email protected] α nanoparticles and human amniotic mesenchymal stromal cells (hAMSCs) were injected into the damaged area in an in-vivo cryogenic injury model in rats. The hydrogel had low module and its average pore size was 204.61 ± 41.41 nm, which were suitable for the migration, proliferation and differentiation of stem cells. In-vitro cell scratch and differentiation assays showed that the imidazole groups and SDF-1α could promote the migration of hAMSCs to injury site and their differentiation into nerve cells. The highest amount of nissl body was detected in the group of GelMA-imid/SDF-1α/hAMSCs hydrogel in the in-vivo model. Additionally, histological analysis showed that GelMA-imid/SDF-1α/hAMSCs hydrogel could facilitate the regeneration of regenerate endogenous nerve cells. In summary, the GelMA-imid/SDF-1α/hAMSCs hydrogel promoted homing and differentiation of hAMSCs into nerve cells, and showed great application potential for the physiological recovery of TBI.
研究领域:
神经科学
·
干细胞疗法
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生物材料
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再生医学
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
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IF 3.743
Lirong Yi,Mei Tian,Chunnan Piao,Gang Gao,Lina Wu,Yan Pan,Jianxiang Liu
Agents that provide protection against irradiation-induced hematopoietic injury are urgently needed for radiotherapy. We examined the effects of the small molecule, 1,2-propanediol (PPD), on total body irradiation (TBI)-induced hematopoietic injury in C57BL/6 mice. PPD administration 1 h before TBI significantly increased hematopoietic parameters such as white blood cell, platelet, red blood cell, and lymphocyte counts in vivo and enhanced the survival of mice exposed to TBI (7.0 and 7.5 Gy). PPD administration 1 h before TBI improved bone marrow (BM) and spleen recovery after TBI, with increases in both BM cellularity and spleen index. The number of colony-forming-units in bone marrow mononuclear cells (BMNCs) in vitro also increased significantly. PPD pretreatment increased the numbers of hematopoietic stem cells and hematopoietic progenitor cells in BM. Importantly, PPD also maintained endogenous antioxidant status by decreasing levels of malondialdehyde and increasing the expression of reduced glutathione, superoxide dismutase and catalase in the serum of irradiated mice. PPD alleviated the levels of apoptosis in HSCs induced by TBI, thus increasing the proportion of dividing BMNCs. These results suggest that PPD protects against TBI-induced hematopoietic injury through the increased activities of antioxidant enzymes and the inhibition of apoptosis in HSCs. PPD increased the serum levels of granulocyte-colony stimulating factor and interleukin-6 irrespective of TBI. In conclusion, these data suggest that PPD acts as a radioprotector against radiation-induced hematopoietic injury.
研究领域:
放射生物学
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血液学
·
药理学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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