International Journal of Nanomedicine
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2025
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IF 6.5
Guangzhe Xu,Chun Ma,Hongyan Chu,Wenxin Hu,Lihua Yang,Shuling Li
Purpose The pathological mechanisms underlying ischemic stroke are highly complex, with the neuroinflammatory response triggered by cerebral ischemia-reperfusion being a major contributor to secondary brain damage. This response significantly impedes neural tissue regeneration. Despite advancements in treatment, current anti-inflammatory strategies remain suboptimal in terms of safety and efficacy. This study aimed to develop an all-natural nanomedicine delivery system for the transnasal administration of puerarin, combined with the endogenous anti-inflammatory peptide Ac2-26, to enhance neuroprotection against ischemic stroke through a synergistic anti-inflammatory approach.Methods In this study, collagen nanoparticles (PueNps) loaded with puerarin were synthesized, followed by the preparation of a chitosan hydrogel. The PueNps and Ac2-26 were co-encapsulated within the hydrogel, resulting in the formation of the PueNps&Ac2-26 gel formulation. The physicochemical properties of this formulation, as well as its biodistribution and anti-ischemic efficacy in the MCAO rat brain, were evaluated.Results In this formulation system, the bioavailability of puerarin and Ac2-26 was enhanced, exhibiting sustained-release properties, which enabled efficient brain-targeted delivery. It effectively alleviated neurological impairment in MCAO rats, reduced the volume of cerebral infarction, and decreased brain water content. Additionally, the PueNps&Ac2-26 gel significantly inhibited neuroinflammation in rats and alleviated oxidative stress.Conclusion The PueNps&Ac2-26 gel is a purely natural and efficient formulation system, offering a promising approach for the clinical treatment of ischemic stroke in the future.
研究领域:
神经科学
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药学
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DOI
PubMed
高影响因子
ACS Applied Bio Materials
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2025
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IF 4.7
Ji Xia,Jin Huang,Yixiao Yan,Chenxin Jian,Jiansheng He,Nisha Wang,Lei Shi,Qiyang Ding,Hao Tian,Wei Gao
Mitochondrial damage occurs as an initial event following ischemic onset, and the extent of mitochondrial dysfunction is highly correlated to the severity of ischemia-induced cell death. Once appropriate therapeutic interventions are provided, the ischemic tissue can be salvaged, which is of great significance in achieving better neurological outcomes. Herein, we developed a nanosized starch as a targeting nanoplatform, featuring effective blood-brain barrier (BBB) penetration through lactoferrin-mediated transcytosis. Notably, the nanostarch-based delivery of Mdivi-1 and Alda-1 enables controlled release in the acidic lysosome of neurons, effectively inhibiting the pathological mitochondrial fission and metabolizing toxic aldehydes, thereby creating protective effects on maintaining mitochondrial function. Moreover, we demonstrated that mitochondrial protection induces a transition from activated pro-death responses to a pro-survival state by reducing the release of pro-apoptotic proteins, significantly contributing to the long-term recovery of neurological function. Overall, our nanostarch provided an in-depth understanding of the delivery of mitochondrial protectants and underscored the potential and utility of mitochondrial protection for ischemic stroke via minimizing neuronal apoptosis.
研究领域:
神经科学
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药理学
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生物医学工程
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Xin Yang,Canhui Hong,Tangfei Guan,ChengGui Zhang,Peiyun Xiao,Yongshou Yang,Huai Xiao,Zhengchun He
Ischemic stroke (IS) is a highly lethal type of cardiovascular and cerebrovascular disease. Improving survival rates and promoting recovery in patients with IS pose significant challenges, however, recent research has identified the gut–brain axis as a therapeutic target. In this study, we evaluated the regulatory effect of Periplaneta americana (L.) extract (PAS840), which has established anti-inflammatory, antioxidant, and neuroprotective effects, on the gut microbiota using a rat model of temporary middle cerebral artery occlusion (tMCAO). We evaluated the protective effects of PAS840 on brain damage in IS rats through TTC (triphenyltetrazolium chloride), Nissl staining, and pathological section analysis. Additionally, we investigated the impact of PAS840 on the gut microbiota and metabolites using 16S rRNA sequencing, untargeted metabolomics of gut contents, and transcriptomics analyses of brain tissues to explore its mechanism of action. PAS840 intervention resulted in significant changes in the gut microbiota, including an increase in the abundance of probiotic flora, decrease in the abundance of harmful flora, and significant changes in metabolite profiles. It also attenuated brain damage, decreased platelet activity, inhibited oxidative stress and genes related to inflammation, and improved neurological function in rats. These findings suggest that PAS840 has preventive and therapeutic effects against IS via the gut–brain axis by regulating the gut microbiota and related metabolites. Accordingly, PAS840 is a candidate therapeutic drug for further research.
研究领域:
神经科学
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药理学
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微生物学
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DOI
PubMed
高影响因子
Molecular Medicine Reports
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2017
·Vol. 16
·期 6
·9361-9366
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IF 1.692
Weixin Zhu,Weihong Qiu,Ailan Lu
Cerebral stroke is a kind of acute cerebrovascular disease with high incidence, morbidity and disability. Treatments against various types of cerebral stroke are limited at preventive measurements due to the lack of effective therapeutic method. The present study aimed to investigate the protective effect of cryptotanshinone (CPT) on cerebral stroke, and investigate the possible mechanism involved in order to develop a novel therapy against stoke. The phosphoinositide 3‑kinase membrane translocation of cerebral stroke rats pretreated with CPT at various concentrations were measured, as well as the phosphorylation of protein kinase B (AKT) and endothelial nitric oxide synthase (eNOS). Additionally, the expression level of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and vascular endothelial growth factor were also assessed using western blotting and reverse transcription‑quantitative polymerase chain reaction. Furthermore, biochemical tests were used to measure the activity of superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) in both the cerebral cortex and peripheral blood. As a result, CPT‑pretreated rats presented declined phosphoinositide 3‑kinase (PI3K) and AKT expression levels, indicating that the PI3K/AKT signaling pathway was inhibited. Increased Bcl‑2 and NO levels in both the cerebral cortex and peripheral blood demonstrated the anti‑apoptosis and blood vessel protection effect of CPT. Furthermore, increased SOD activity and declined MDA levels demonstrated suppressed lipid peroxidation. In conclusion, CPT exhibited a protective effect against cerebral stroke through inhibition of the PI3K/AKT‑eNOS signaling pathway. These results suggested the potential of CPT as a promising agent in the treatment of cerebral stroke.
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
Smart Medicine
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2023
·Vol. 2
·期 1
·e20220037
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IF 0
Yimeng Shu,Hui Shen,Minghua Yao,Jie Shen,Guo-Yuan Yang,Hangrong Chen,Yaohui Tang,Ming Ma
Mesenchymal stem cell (MSC)-based therapy has provided a promising strategy for the treatment of ischemic stroke, which is still restricted by the lack of long-term cell tracking strategy as well as the poor survival rate of stem cells in ischemic region. Herein, a dual-functional nanoprobe, cobalt protoporphyrin-induced nano-self-assembly (CPSP), has been developed through a cobalt protoporphyrin IX (CoPP) aggregation-induced self-assembly strategy, which combines CoPP and superparamagnetic iron oxide (SPION) via a simple solvent evaporation-driven method. Without any additional carrier materials, the obtained CPSP is featured with good biocompatibility and high proportions of active ingredients. The SPIONs in CPSPs form a cluster-like structure, endowing this nano-self-assembly with excellent T 2 -weighted magnetic resonance (MR) imaging performance. Furthermore, the CoPP released from CPSPs could effectively protect MSCs by upregulating heme oxygenase 1 (HO-1) expression. The in vivo cell tracing capacity of CPSPs is confirmed by monitoring the migration of labeled MSCs with MR imaging in a middle cerebral artery occlusion mouse model. More importantly, the sustained release of CoPP from CPSPs improves the survival of transplanted MSCs and promotes neural repair and neurobehavioral recovery of ischemic mice. Overall, this work presents a novel dual-functional nanoagent with an ingenious design for advancing MSC-based therapy.
研究领域:
生物医学工程
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神经科学
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干细胞治疗
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分子影像学
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DOI
Stem Cell Research & Therapy
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2025
·Vol. 16
·期 1
·1-18
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IF 7.3
Mao Shihui,Lan Ting,Sun Yimei,Li Lin,Jiang Weifeng,Xu Jiadong,Feng Yan,Hu Huiqin,Fang Yan,Xu Lanxi,Chu Lisheng
Background Bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) show therapeutic promise for ischemic stroke (IS). Preconditioning MSCs with drugs can modulate the cargo composition and function of their derived EVs. This study investigated the therapeutic effects and underlying mechanisms of EVs derived from tetramethylpyrazine (TMP)-preconditioned BMSCs (TMP-BMSC-EVs) in IS.Methods EVs were isolated from BMSCs pretreated with or without TMP by differential centrifugation. The therapeutic efficacy of EVs was evaluated in a rat model of middle cerebral artery occlusion (MCAO) through neurological function assessments and infarct volume quantification. The expression of miR-486 and its roles in regulating microglia/macrophage polarization and neurogenesis, as well as the mechanistic targets, were examined by real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence staining, and Western blotting.Results TMP-BMSC-EVs exerted superior therapeutic efficacy compared to BMSC-EVs. Mechanistically, TMP-BMSC-EVs were enriched with miR-486, which promoted microglia/macrophage M2 polarization and neurogenesis, while downregulating phosphatase and tensin homolog (PTEN) and phosphorylated NF-κB (p-NF-κB) protein levels, and upregulating phosphorylated Akt (p-Akt) expression. Transfection with a miR-486 inhibitor abolished the beneficial effects of TMP-BMSC-EVs, which could be counteracted by the PTEN inhibitor bisperoxovanadium (bpV).Conclusion sTMP-BMSC-EVs could significantly promote neural repair by driving microglia/macrophage M2 polarization and enhancing neurogenesis through miR-486-mediated PTEN inhibition, thereby offering a promising treatment strategy for IS.
研究领域:
神经科学
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干细胞研究
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
CURRENT NEUROVASCULAR RESEARCH
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2025
·Vol. 22
·期 1
·70-85
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IF 1.7
Ziteng Yang,Yuanqi Zuo,Guangyun Wang,Ning Wang
Introduction: The endothelial barrier is composed of brain microvascular endothelial cells (BMECs) and tight junction (TJ) proteins. Musk is a valuable ingredient in Traditional Chinese Medicine (TCM). It is used in the treatment of stroke because of its ability to induce resuscitation. The core component of musk is muscone. Previous studies have evidenced that muscone may be involved in the treatment of ischemic stroke (IS), but the underlying mechanism is still unclear. The main objective of this study was to explore the protective effect of muscone on OGD/R-induced endothelial barrier disruption and determine its underlying mechanism. Methods: OGD/R-induced damage to BMECs was assessed using the MTT and LDH assays. The apoptosis level in BMECs was determined using western blot and Hoechst staining. Western blot, immunofluorescence, and phalloidin staining were used to assess the expressions of TJ proteins and pathway proteins expression. A monolayer cell barrier was constructed using BMECs in vitro, and the permeability of the barrier was assessed by TEER as well as the transmissivity of sodium fluorescein. Molecular docking, DARTS, and CETSA were used to verify the regulatory effect of muscone on the pathway. Results: Muscone reduced OGD/R-induced apoptosis of BMEC cells, inhibited the degradation of TJ proteins, promoted the coherent expression of ZO-1 on the membrane, and restored TEER. Mechanistic studies showed that H-89 reversed the promoting effects of muscone on pathway proteins and promoted the disassembly of the actin cytoskeleton, which, in turn, promotes BMEC apoptosis and TJ protein degradation, ultimately disrupting the endothelial barrier. Discussion: The inhibition of BMEC apoptosis and improvement of endothelial barrier damage by muscone may be an important mechanism for treating ischemic stroke. Conclusion: We demonstrated that muscone could reduce OGD/R-induced hyperpermeability of the brain endothelial barrier by activating the PKA/RHOA/MLC pathway.
研究领域:
神经科学
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药理学
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中医中药
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2025
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IF 9.6
Dingfu Wang,Dan Li,Xiaolin Liu,Shixin Wang,Yile Fan,Ling Lu,Chuanbin Shen,Chunxia Li
Thrombolytic therapy for cardiovascular and cerebrovascular diseases is significantly limited by the short half-life, inadequate targeting specificity, and hemorrhagic complications of conventional therapeutic agents. To overcome these challenges, we developed a dual-functional nanogel (PGS-SP@UK) that integrates P-selectin-mediated thrombus targeting with ROS-responsive drug release. Taking advantage of the P-selectin targeting capability of polyguluronate sulfate (PGS), we synthesized the sulfated polysaccharide with selenocystamine and pinacol phenylboronate (PBAP) to construct an amphiphilic copolymer capable of encapsulating urokinase (UK). Notably, this nanogel exhibited H 2 O 2 -triggered UK release (85.79%) while maintaining great stability under physiological conditions. In vitro studies confirmed its neuroprotective effects through modulation of the ferroptosis signaling pathway in an OGD/R-induced model. In vivo studies revealed efficient blood-brain barrier penetration and thrombus-specific accumulation, achieving 84.3% recovery in cerebral infarct area through synergistic thrombolysis and oxidative stress mitigation. Our study presents an innovative drug delivery system with significant potential for clinical ischemic stroke treatment. Statement of Significance Conventional thrombolytic agents suffer from poor targeting specificity and severe bleeding complications, limiting their clinical efficacy in ischemic stroke treatment. We designed a dual-functional nanogel (PGS-SP@UK) that uniquely integrates P-selectin-mediated active targeting with ROS-responsive drug release mechanisms. This innovative design represents a system to combine polyguluronate sulfate-based thrombus recognition with oxidative stress-triggered urokinase liberation. Our nanogel achieves unprecedented selectivity through dual targeting: bioactive targeting via P-selectin binding and microenvironmental responsiveness to pathological ROS levels. In vivo validation demonstrated exceptional therapeutic outcomes with 84.3% cerebral infarct recovery while eliminating systemic hemorrhagic risks. This breakthrough establishes a new therapeutic paradigm that transcends current limitations through synergistic thrombolysis and neuroprotection, offering transformative potential for precision medicine in thrombotic disorders.
研究领域:
生物材料
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纳米医学
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脑血管病学
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药物递送系统
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氧化应激
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神经保护
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血栓靶向
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产品关联
DOI
PubMed
高影响因子
Journal of Neuroimmune Pharmacology
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2025
·Vol. 20
·期 1
·1-15
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IF 3.5
Xiao Lifang,Wang Mengyao,Li Jingjing,Wang Haoran,Pu Niu,Bo Xitong,Chen Fuxiang,Zhou Yilong,Cheng Qiong
The underlying pathological mechanism of ischemic stroke is complex, with oxidative stress and inflammation being two key factors that are intertwined and mutually influential. They also serve as important potential targets for the intervention of cerebral ischemia. Pyrroloquinoline quinone (PQQ) is known for its neuroprotective properties and the ability to modulate immune system function. Previous studies have demonstrated that PQQ mitigates brain infarction in rodent models of cerebral ischemia; however, the neuroprotective mechanisms underlying PQQ’s effects against ischemic brain injury are not yet fully understood. This study used an MCAO rat model, an OGD model with SH-SY5Y cells, and an LPS-activated BV2 microglia model to investigate the neuroprotective functions of PQQ on brain ischemia. Using various experimental methods, including cell viability assays, oxidative stress damage assessments, inflammatory factor expression analysis, behavioral tests in animal models, and histological evaluations, we discovered that PQQ activates the nuclear translocation of Nrf2 in neurons, thereby enhancing downstream antioxidant responses. Additionally, PQQ inhibits NF-kB activation in microglia and suppresses their M1-type polarization, leading to decreased pro-inflammatory mediators’ expression levels and reduced neural inflammatory damage. These results provide further insights into the neuroprotective mechanisms involved in PQQ’s effects against cerebral ischemia and may offer evidence for its translational application in treating brain ischemia. Graphical
研究领域:
神经科学
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药理学
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生物化学
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细胞生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
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2025
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IF 10.2
Chenjie Xia,Changhui Hu,Rui Xu,Feihong Zhuo,Mengfei Yang,Yinjia Li,Zixuan Shan,Cheng Xu,Yutong Wang,Zhipeng Chen
Ischemic stroke is a neurological disease characterized by high morbidity and mortality. A key pathological mechanism involves rapid restoration of blood oxygen in the infarcted area, which triggers oxidative stress and inflammatory responses leading to neuronal damage. The complex etiology of the disease poses challenges to single-target pharmacotherapy, necessitating the development of multi-targeted combination drug treatments. Reports showed that water- and lipid-soluble components of Danshen, exert synergistic neuroprotective effects. However, the disparate physicochemical properties of these compounds lead to differential release kinetics, hampering the therapeutic efficacy. Furthermore, the blood-brain barrier (BBB) presents a formidable obstacle to the penetration of water-soluble constituents. Here, we developed a novel biomimetic drug delivery system utilizing hollow polydopamine coated with red blood cell membranes. Water-soluble (W) and lipid-soluble (L) components of Danshen were loaded at distinct membrane regions to facilitate synchronized release profile. Additionally, borneol was used to modify the membrane to enhance the BBB penetration capacity. Mechanism study revealed that W and L possess synergistic effect through inhibiting NF-κB and TNF-α pathways. In summary, this delivery system enables concurrent loading and efficient brain delivery of multiple constituents, thereby promoting neurological recovery and presenting a promising therapeutic strategy for ischemic stroke.
研究领域:
神经病学
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药剂学
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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
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产品关联
DOI
PubMed
高影响因子
Exploration
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2025
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IF 22.5
Xiaojing Shi,Shuya Wang,Tingli Xiong,Ruishi Li,Wenxuan Zheng,Wensheng Chen,Tianjiao Zhao,Yongqi Yang,Xiaohong Ying,Weimin Qi,Yingci Xia,Jue Wang,Yuqi Zhang,Qiong Huang,Yayun Nan,Kelong Ai
Protecting neuronal mitochondria by eliminating the mitochondrial ROS (mtROS) storm is crucial to abrogate the neuronal damage cascade of ischemic stroke ischemia reperfusion (ISIR), which is a long-standing challenge in the field of ischemic stroke (IS). Existing blood-brain barrier (BBB) penetration methods are usually unable to distinguish between healthy brain tissue and cerebral infarction tissue, and BBB targeting is not compatible with mitochondrial targeting, resulting in a huge barrier to the specific elimination of mtROS in neuronal mitochondria in ISIR. This study introduces an elegantly designed tannic acid, polydopamine, and Mo-based heteropolyacid ternary composite nanomedicine (TPM), which not only has a superb ability to eliminate multiple ROS thanks to the introduction of polydopamine, but also can actively recognize the injured BBB site, specifically enter the neurons in the cerebral infarction area, and then highly specifically target the mitochondria of neurons to efficiently eliminate mtROS. TPM could significantly inhibit neuronal apoptosis by protecting mitochondria and eliminate inflammation by inhibiting activation of the STING pathway, thereby significantly reducing the size of cerebral infarction. This sequential targeting of TPM from the injured BBB to neuronal mitochondria provides a promising strategy to treat ISIR in the clinical setting.
研究领域:
纳米医学
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神经病学
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脑卒中治疗
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活性氧清除
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药物递送
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2024
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IF 15.8
Xingping Quan,Chang Liu,Jinfen Chen,Yiyang Li,Zhen Yuan,Ying Zheng,Greta S. P. Mok,Ruibing Wang,Yonghua Zhao
Thromboembolic stroke constitutes the majority of brain strokes, resulting in elevated mortality and morbidity rates, as well as significant societal and economic burdens. Although intravenous thrombolysis serves as the standard clinical treatment, its narrow therapeutic window and the inflammatory response induced by tissue plasminogen activator (tPA) administration limit its efficacy. In the initial stages of stroke, the abrupt cessation of blood flow leads to an energy metabolism disorder, marked by a substantial decrease in adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH) levels, causing irreversible damage to neural cells. In this study, we introduce a neutrophil-mimetic, microalgae-derived upconversion photosynthetic nanosystem designed for targeted treatment of thromboembolic stroke. This system features upconversion nanoparticles coated with a thylakoid membrane and wrapped in an activated neutrophil membrane, further decorated with ROS-responsive thrombolytic tPA on its surface. The neutrophil-mimetic design facilitates high targeting specificity and accumulation at the thrombus site after intravenous administration. Upon exposure to elevated levels of reactive oxygen species (ROS) at the thrombus location, the nanosystem promptly demonstrated potent thrombolytic efficacy through the surface-modified tPA. Furthermore, near-infrared II (NIR-II) laser irradiation activated the generation of ATP and NADPH, which inhibited inflammatory cell infiltration, platelet activation, oxidative stress, and neuronal injury. This constructed nanoplatform not only showcases exceptional targeting efficiency at the stroke site and controllable release of the thrombolytic agent but also facilitates ATP/NADPH-mediated thrombolytic, anti-inflammatory, antioxidative stress, and neuroprotective effects. Additionally, it offers valuable insights into the potential therapeutic applications of microalgae-based derivatives in managing thromboembolic stroke.
研究领域:
纳米技术
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生物医学工程
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神经科学
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药学
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光化学
✓ 已验证
DOI
PubMed
高影响因子
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