Journal of Translational Medicine
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2025
·Vol. 23
·期 1
·1-20
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IF 7.5
Zhang Bin,Bai Miao,Yang Mengshi,Wang Yumei,Chen Xiyu,Liu Baiyun,Shi Guangzhi
Background Glucocorticoids (GCs) have been widely used in the treatment of severe traumatic brain injury (TBI) to inhibit neuroinflammation and alleviating brain edema and cannot be replaced by other drugs. However, their systemic application still faces many obstacles, such as the poor blood-brain-barrier (BBB) penetration and severe side effects. Therefore, new treatment strategy or compounds are urgently needed in clinic.Methods Herein, an injectable nanocomposite hydrogel is developed as a biofunctionalized delivery platform for intraoperative administration of dexamethasone (DEX) after TBI. By using a mice TBI model, the safety and efficacy of the nanohydrogels in treating BBB disruption, brain edema and nerve injury were evaluated after TBI.Results The hydrogel is composed of polysaccharide matrix (carboxymethyl chitosan and oxidized dextran) and mesoporous polydopamine (MPDA) nanoparticles loaded with DEX (MPDA@DEX@gel) that could realize in situ injection, self-assembly, a high DEX loading rate and sustained release around the lesion. The MPDA@DEX@gel exhibits excellent antibacterial and hemostatic properties, good biocompatibility and antioxidation, and self-healing capability in vitro. These in vitro and in vivo results show that local application of MPDA@DEX@gel not only alleviates brain edema, promotes neuronal survival, and improves neurological function by restoring the integrity of BBB and inhibiting neuroinflammation after TBI, but also effectively avoids the peripheral and central side effects.Conclusion Our study provides a promising treatment strategy for the rational use of GCs in patients with severe TBI.
研究领域:
神经科学
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药剂学
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材料科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
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2025
·Vol. 55
·期 3
·1-14
·
IF 5.8
Yixuan Ma,Yimin Huang,Xuyang Liu,Liwu Jiao,Hongtao Zhu,Zhiye Chen,Zhuojin Wu,Yuanzhong Shen,Kehan Lin,Feng Hu,Kai Shu
The present study investigated the mechanisms by which aquaporin 1 (AQP1) influences microglial polarization and neuroinflammatory processes in traumatic brain injury (TBI). A model of TBI was generated in AQP1‑knockout mice to assess the impact of AQP1 deletion on inflammatory cytokine release, neuronal damage and cognitive function. Immunofluorescence, reverse transcription‑quantitative PCR, western blotting and enzyme‑linked immunosorbent assay were employed to evaluate pro‑inflammatory and anti‑inflammatory markers. Behavioral assessments, including the Barnes maze, were performed to determine cognitive outcomes. Moreover, AQP1 knockout inhibited the activation of inflammation‑related signaling pathways, including nuclear factor‑κB, Janus kinase/signal transducer and activator of transcription, phosphoinositide 3‑kinase/protein kinase B and extracellular signal‑regulated kinase/mitogen‑activated protein kinase pathways. Further studies indicated that the AQP1 inhibitor m‑phenylenediacrylic acid demonstrated significant neuroprotective effects in a mouse model of TBI. These findings suggested that AQP1 may be essential in post‑TBI inflammatory responses and neuronal injury, establishing a theoretical foundation for future therapies aimed at AQP1.
研究领域:
神经科学
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炎症生物学
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分子医学
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产品关联
DOI
PubMed
高影响因子
NEUROREPORT
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2022
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IF 1.703
Peng-Cheng Zhao,Zhen-Shan Huang,Shao-Nian Xu,Peng-Cheng Deng,Feng Qian,Jian Shi,Yong-Ming Zhang
To explore the effects of high cervical spinal cord electrical stimulation (cSCS) on the recovery of neurological function and its possible mechanism in rats with traumatic brain injury (TBI). 72 rats were randomly divided into: (1) a sham group; (2) a traumatic brain injury (TBI) group; (3) a TBI+cSCS group; (4) a LY294002+TBI+cSCS group. The degree of neurological dysfunction was evaluated by modified Neurological severity score (mNSS). The pathological changes of the brain tissue in the injured area were observed by HE staining, and the apoptosis of neuron cells were observed by TUNEL staining. The expressions of BDNF and VEGFmRNA were detected by polymerase chain reaction (PCR), and the expressions of p-AKT, AKT, Bcl-2, Bax and caspase-3 proteins were detected by western blot. Compared with that of the TBI and LY294002+TBI+cSCS groups, the mNSS of the TBI+cSCS group were significantly lower on day 3 and 7 ( P <0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the apoptosis of neuron cells in the TBI+cSCS group decreased significantly ( P < 0.05). Compared with the TBI and LY294002+TBI+cSCS group, the expression of Bcl-2 protein increased and the expressions of Bax and Caspase-3 proteins decreased in the TBI+cSCS group ( P < 0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the intensity of p-Akt/Akt in the TBI+cSCS group increased ( P < 0.05). We found that cSCS had a protective effect on neuron cells after craniocerebral injury and could improve neurological dysfunction in rats, the mechanism of which might be that cSCS made the PI3K/Akt pathway more active after TBI.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Tissue Engineering Part A
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2014
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IF 0
Shane Gao,Peng Zhao,Chao Lin,Yuxi Sun,Yilei Wang,Zhichong Zhou,Danjing Yang,Xianli Wang,Hongzhen Xu,Fei Zhou,Limei Cao,Wei Zhou,Ke Ning,Xu Chen,Jun Xu
Multipotent human adipose-derived stromal/stem cells (hADSCs) hold a great promise for cell-based therapy for many devastating human diseases, such as spinal cord injury and stroke. If exogenous hADSCs can be cultured in a three-dimensional (3D) scaffold with effective proliferation and differentiation capacity, it will better mimic the in vivo environment, which will have profound impact on the therapeutic application of hADSCs. In this study, a group of elastic-dominant, porous bioscaffolds from photocurable chitosan and gelatin were fabricated and proven to be biocompatible with both hADSCs and hADSC-derived neuron-like cells (hADSC-NLCs) in vitro. The identity of harvested hADSCs was confirmed by their positive immunostaining of mesenchymal stem cell surface markers, CD29, CD44, and CD105, and also positive expression of stem markers, Sox-2, Oct-4, c-Myc, Nanog, and Klf4. Their multipotency was further confirmed by trilineage differentiation of hADSCs toward adipocyte, osteoblast, and chondrocyte. It was found that hADSCs could be conditioned to differentiate into neurons in vitro as determined by immunostaining the markers of Tuj1, MAP2, NeuN, and Synapsin. The hADSCs and hADSC-NLCs were proven to be biocompatible with 3D scaffold, which actually facilitated the proliferation and differentiation of hADSCs in vitro, by MTT assay and their neuronal gene expression profiling. Moreover, hADSC-NLCs, which were mixed with 3D scaffold and transplanted into traumatic brain injury mouse model, survived in vivo and led to the better repair of the damaged brain area. The immunohistochemical studies revealed that 3D scaffold indeed improved the viability of transplanted cells, their ability to incorporate into the in vivo neural circuit, and their capacity for tissue repair. This study indicates that hADSCs would have great therapeutic application potential as seeding cells for in vivo transplantation to treat various neurological diseases when co-applied with porous chitosan/gelatin bioscaffolds.
研究领域:
再生医学
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干细胞研究
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组织工程
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神经科学
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产品关联
DOI
PubMed
Frontiers in Bioscience-Landmark
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2023
·Vol. 28
·期 5
·93
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IF 3.1
Chenglong Sun,Wenhao Zheng,Linjie Wang,Quan Du
Background: Gastrodin (Gas) exhibits anti-inflammatory properties against diseases associated with the central nervous system (CNS). This study aimed to investigate the potential neuroprotective role of Gas in traumatic brain injury (TBI). Methods: A rat TBI model was established in male adult Sprague-Dawley (SD) rats by controlled cortical impingement (CCI), and lipopolysaccharide (LPS) was applied to induce the activation of BV2 microglia and HT22 hippocampal neurons. Neurological deficits, motor function and brain water content were evaluated in TBI rats. TUNEL and Nissl’s staining were applied to measure neuronal degeneration and apoptosis. Microglial activation, the mRNA and protein profiles of pro-inflammatory cytokines were tested by immunohistochemistry (IHC), quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: Gas significantly reduced neurological deficits, cerebral edema, and neuronal apoptosis and improved motor function in TBI mice. In addition, Gas inactivated microglia and blocked the production of pro-inflammatory cytokines on the damaged side of the TBI rat brain. In vitro, Gas attenuated BV2 microglia inflammation and reduced HT22 hippocampal neuronal apoptosis. On the other hand, Gas activated the PKA/CREB/BDNF pathway both in vivo and in vitro. Conclusions: Gas blocks microglial activation-mediated inflammation through the PKA/CREB/BDNF pathway, thereby improving neurobehavioral function after TBI, which provides a potential therapeutic benefit for treating TBI.
研究领域:
神经科学
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药理学
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神经病学
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DOI
PubMed
高影响因子
BIOMATERIALS
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2025
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IF 12.9
Bixue Wang,Qiya Zhang,Changsheng Liu,Xi Chen
Traumatic brain injury (TBI), an intractable disorder of the central nervous system (CNS), is a leading cause of long-term disability and mortality in humans worldwide. However, there is still no effective therapy for TBI, and an important reason for this is TBI-induced immunodepression, which renders TBI patients with low resistance to infections and aggravated brain damage. In this study, a multifunctional extracellular matrix hydrogel was constructed for the treatment of TBI in terms of both counteracting the immunodepression and enhancing neurogenesis. The stromal cell-derived factor-1α (SDF-1α)-loaded hyaluronic acid (HA)/decellularized brain extracellular matrix (BM) hydrogel (SDF@HA/BM) not only mimicked the composition and the biological cues of brain extracellular matrix, but also exhibited the injectability, self-healing, and mechanical properties close to those of brain tissue. The SDF@HA/BM hydrogel protected activated immune cells from dysfunction during the acute phase of TBI for normal levels of inflammatory cytokines, thereby creating a favorable immune microenvironment for subsequent neurogenesis. The SDF-1α and the BM synergistically promoted neurogenesis after TBI by recruiting endogenous neural stem/progenitor cells and inducing their differentiation into neurons. In vivo results demonstrated that the SDF@HA/BM hydrogel exhibited desirable therapeutic effects in severe TBI mice through facilitating brain tissue remodeling and neurological function recovery, including limb balance, autonomous locomotion, and spatial learning and memory abilities, and relieving depression and anxiety. Our work provides a novel strategy for TBI treatment in terms of restoring immune homeostasis and enhancing neurogenesis using advanced biomaterials.
研究领域:
神经科学
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材料科学
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再生医学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Cell Communication and Signaling
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2025
·Vol. 23
·期 1
·1-21
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IF 8.9
Li Lei,Peng Ruilong,Wang Cong,Chen Xin,Gheyret Dilmurat,Guan Siyu,Chen Bo,Liu Yafan,Liu Xilei,Cao Yiyao,Han Cha,Xiong Jianhua,Li Fanjian,Lu Taoyuan,Jia Haoran,Li Kaiji,Wang Jinchao,Zhang Xu,Xu Jianye,Wang Yajuan,Xu Xin,Li Tuo,Zhang Jianning,Zhang Shu
Neutrophils are the first responders among peripheral immune cells to infiltrate the central nervous system following a traumatic brain injury (TBI), triggering neuroinflammation that can exacerbate secondary tissue damage. The precise molecular controls that dictate the inflammatory behavior of neutrophils post-TBI, however, remain largely elusive. Our comprehensive analysis of the molecular landscape surrounding the trauma in TBI mice has revealed a significant alteration in the abundance of β2 integrin (ITGB2), predominantly expressed by neutrophils and closely associated with immune responses. Using the fluid percussion injury (FPI) mouse model, we investigated the therapeutic efficacy of Rovelizumab, an agent that blocks ITGB2. The treatment has demonstrated significant improvements in neurologic function in TBI mice, attenuating blood–brain barrier permeability, mitigating oxidative stress and inflammatory mediator release, and enhancing cerebral perfusion. Moreover, ITGB2 blockade has effectively limited the adherence, migration, and infiltration of neutrophils, and has impeded the formation of neutrophil extracellular traps (NETs) upon their activation. Finally, it was demonstrated that ITGB2 mediates these effects mainly through its interaction with intercellular adhesion molecule-1 (ICAM 1) of endotheliocyte. These findings collectively illuminate ITGB2 as a crucial molecular switch that governs the adverse effects of neutrophils post-TBI and could be targeted to improve clinical outcome in patients.
研究领域:
神经科学
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免疫学
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创伤医学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
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2023
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IF 6.2
Cong Wei,Peipei Li,Lixin Liu,Hong Zhang,Tianyu Zhao,Yongming Chen
Following brain trauma, secondary injury from molecular and cellular changes causes progressive cerebral tissue damage. Acute/chronic neuroinflammation following traumatic brain injury (TBI) is a key player in the development of secondary injury. Rapidly elevated cell-free DNAs (cfDNAs) due to cell death could lead to production of inflammatory cytokines that aggravate TBI. Herein, we designed poly(amino acid)-based cationic nanoparticles (cNPs) and applied them intravenously in a TBI mice model with the purpose of scavenging cfDNA in the brain and suppressing the acute inflammation. In turn, these cNPs could effectively eliminate endogenous cfDNA, inhibit excessive activation of inflammation, and promote neural functional recovery.
研究领域:
神经科学
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药学
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生物医学工程
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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
CELL
·
2024
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IF 45.5
Yuanlong Zhang,Mingrui Wang,Qiyu Zhu,Yuduo Guo,Bo Liu,Jiamin Li,Xiao Yao,Chui Kong,Yi Zhang,Yuchao Huang,Hai Qi,Jiamin Wu,Zengcai V. Guo,Qionghai Dai
A comprehensive understanding of physio-pathological processes necessitates non-invasive intravital three-dimensional (3D) imaging over varying spatial and temporal scales. However, huge data throughput, optical heterogeneity, surface irregularity, and phototoxicity pose great challenges, leading to an inevitable trade-off between volume size, resolution, speed, sample health, and system complexity. Here, we introduce a compact real-time, ultra-large-scale, high-resolution 3D mesoscope (RUSH3D), achieving uniform resolutions of 2.6 × 2.6 × 6 μm 3 across a volume of 8,000 × 6,000 × 400 μm 3 at 20 Hz with low phototoxicity. Through the integration of multiple computational imaging techniques, RUSH3D facilitates a 13-fold improvement in data throughput and an orders-of-magnitude reduction in system size and cost. With these advantages, we observed premovement neural activity and cross-day visual representational drift across the mouse cortex, the formation and progression of multiple germinal centers in mouse inguinal lymph nodes, and heterogeneous immune responses following traumatic brain injury—all at single-cell resolution, opening up a horizon for intravital mesoscale study of large-scale intercellular interactions at the organ level.
研究领域:
生物医学工程
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神经科学
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免疫学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2023
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IF 9.5
Ziying You,Yue Yu,Tie Hua Wang,Chenglin Wang,Ding Xiong,Yu Shi,Zhenming Wang,Ling Ye
Increased intracranial pressure after traumatic brain injury (TBI) is an urgent problem in clinical practice. A pliable hydrogel is preferred for cranioplasty applications after TBI since it can protect brain tissue and promote bone healing. Nevertheless, biohydrogels for cranial bone regeneration still face challenges of poor mechanical properties, large swelling ratios, and low osteogenesis activity. Herein, inspired by Hofmeister effects, biopolymer hydrogels composed of protein and polysaccharides were treated with a Hofmeister series including a series of monovalent and divalent anions. Our results reveal that the divalent anion-cross-linked biohydrogels exhibit stronger mechanical properties and lower swelling ratios compared with monovalent-anion treated gels. Intriguingly, the divalent HPO42– anion induced biohybrid hydrogels with excellent mechanical behaviors (3.7 ± 0.58 MPa, 484 ± 76.7 kPa, and 148.3 ± 6.85 kJ/m3), anti-swelling capability (16.7%), and gradual degradation ability, significantly stimulating osteogenic differentiation and in vivo cranial bone regeneration. Overall, this study may provide new insights into the design of biomimetic hydrogels for treating cranial bone defects after TBI.
研究领域:
生物材料
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组织工程
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生物医学工程
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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