Tetrahedral Framework Nucleic Acids as an Efficient Nasal‐to‐Brain Delivery Carrier via Neural Transport Pathways

Advanced Functional Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Abstract In the development of nasal‐to‐brain (N2B) drug delivery systems, key challenge lies in penetrating mucus, crossing nasal epithelial barrier, and achieving broad distribution within central nervous system (CNS) while ensuring biosafety. Non‐biomimetic systems raise concerns regarding metabolism, biomimetic though safer, still face premature release into tissues limited distribution. Moreover, N2B transport mechanisms most existing remain inadequately understood. This study proposed an efficient based on tetrahedral framework nucleic acids (tFNAs). These nanostructures, ≈10 nm size, possess densely negative‐charged surfaces that help evade protein capture facilitate rapid penetration mucus layer, travel along olfactory trigeminal nerve axons to achieve widespread CNS. The pathway is clearly elucidated. Additionally, tFNAs are used deliver peptide via intranasal administration treat sepsis‐associated encephalopathy (SAE). Results showed tFNA‐NAP can regulate microglial activity, reduce neuronal damage, improve behavioral outcomes. both short‐ long‐term safety experiments revealed no adverse effects. summary, tFNA‐based fills a gap this field, offering non‐invasive treatment approach for CNS diseases.

Язык: Английский

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Traditional Chinese Medicine Borneol‐Based Polymeric Micelles Intracerebral Drug Delivery System for Precisely Pathogenesis‐Adaptive Treatment of Ischemic Stroke

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Abstract The scarcity of effective neuroprotective agents and the presence blood‐brain barrier (BBB)‐mediated extremely inefficient intracerebral drug delivery are predominant obstacles to treatment cerebral ischemic stroke (CIS). Herein, ROS‐responsive borneol‐based amphiphilic polymeric NPs constructed by using traditional Chinese medicine borneol as functional blocks that served surface brain‐targeting ligand, inner hydrophobic core for efficient loading membrane‐permeable calcium chelator BAPTA‐AM, structural component. In MCAO mice, nanoformulation (polymer: 3.2 mg·kg −1 , BAPTA‐AM: 400 µg·kg ) reversibly opened BBB achieved high brain biodistribution up 12.7%ID/g total administered dose after 3 h post single injection, effectively restoring intracellular Ca 2+ redox homeostasis, improving histopathology, inhibiting mitochondrial PI3K/Akt/Bcl‐2/Bax/Cyto‐C/Caspase‐3,9 apoptosis pathway rescuing dying neurons (reduced cell from 59.5% 7.9%). It also remodeled inflammatory microenvironment in penumbra astrocyte over‐activation, reprogramming microglia polarization toward an anti‐inflammatory phenotype, blocking NF‐κB/TNF‐ α /IL‐6 signaling pathways. These interventions eventually reduced infarction area 96.3%, significantly improved neurological function, restored blood flow reperfusion 66.2% ≈100%, all while facilitating repair avoiding edema. This provides a potentially multiple‐stage sequential strategy clinical CIS.

Язык: Английский

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The roles and therapeutic potential of exosomal non-coding RNAs in microglia-mediated intercellular communication

International Immunopharmacology, Год журнала: 2025, Номер 148, С. 114049 - 114049

Опубликована: Янв. 16, 2025

Язык: Английский

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The Role of Microglia in Perioperative Pain and Pain Treatment: Recent Advances in Research

Journal of Integrative Neuroscience, Год журнала: 2025, Номер 24(2)

Опубликована: Янв. 25, 2025

Microglia play a crucial role in monitoring the microenvironment of central nervous system. Over past decade, microglia field pain has gradually been unraveled. activation not only releases proinflammatory factors that enhance nociceptive signaling, but also participates resolving pain. Opioids induce activation, which enhances phagocytic activity and release neurotoxic substances. Conversely, reduces opioid efficacy results tolerance. The application research to clinical management drug development is promising challenging area. Microglia-targeted therapies may provide new avenues for management.

Язык: Английский

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Postnatal downregulation of Fmr1 in microglia promotes microglial reactivity and causes behavioural alterations in female mice

Molecular Autism, Год журнала: 2025, Номер 16(1)

Опубликована: Март 7, 2025

Fragile X syndrome is caused by the loss of Fmr1 gene expression. Deletion in various neuronal and non-neuronal subpopulations brain mice leads to cell-type-specific effects. Microglia, immune cells critical for refinement circuits during development, have been implicated neurodevelopmental disorders, including fragile syndrome. However, it unknown whether reduced expression microglia molecular behavioral phenotypes. We downregulated early late postnatal development studied effect on microglial morphology distinct behaviours. Female, but not male, adult with downregulation exhibited reactive phenotypes, enhanced self-grooming alterations social interaction. Downregulation induced a milder phenotype, characterized impaired preference novelty without affecting morphology. The its encoded protein FMRP contributes behavioural phenotypes sex-specific manner.

Язык: Английский

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Piezo1 in microglial cells: Implications for neuroinflammation and tumorigenesis

Channels, Год журнала: 2025, Номер 19(1)

Опубликована: Апрель 13, 2025

Microglia, the central nervous system (CNS) resident immune cells, are pivotal in regulating neurodevelopment, maintaining neural homeostasis, and mediating neuroinflammatory responses. Recent research has highlighted importance of mechanotransduction, process by which cells convert mechanical stimuli into biochemical signals, microglial activity. Among various mechanosensitive channels, Piezo1 emerged as a key player microglia, influencing their behavior under both physiological pathological conditions. This review focuses on expression role particularly context neuroinflammation tumorigenesis. We explore how mediates responses to changes within CNS, such alterations tissue stiffness fluid shear stress, common conditions like multiple sclerosis, Alzheimer's disease, cerebral ischemia, gliomas. The also discusses potential targeting for therapeutic intervention, given its involvement modulation activity impact disease progression. integrates findings from recent studies provide comprehensive overview Piezo1's mechanistic pathways function. These insights illuminate new possibilities developing targeted therapies addressing CNS disorders with mechanics.

Язык: Английский

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Drivers and shapers of macrophages specification in the developing brain

Current Opinion in Immunology, Год журнала: 2025, Номер 94, С. 102558 - 102558

Опубликована: Апрель 15, 2025

Язык: Английский

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MK5 Regulates Microglial Activation and Neuroinflammation in Experimental Stroke Models

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(4)

Опубликована: Апрель 1, 2025

ABSTRACT Objective Microglial activation plays a crucial role in neuroinflammation following ischemic stroke. This study was conducted to investigate the and potential mechanisms of MK5 within microglial cells inflammatory response stroke mice vivo vitro. Methods Microglia‐specific conditional knockout (MK5 cKO) their control f/f ) were subjected middle cerebral artery occlusion (MCAO). BV2 (a mouse cell line) transfected with small interfering RNA (siRNA) knock down levels subsequently exposed oxygen–glucose deprivation/reperfusion (OGD/R) simulate conditions Following MCAO, behavioral tests infarct volume measurements conducted. Levels cytokines markers evaluated using qPCR Western blotting, while immunofluorescence employed observe activation. Additionally, blotting performed assess phosphorylation HSP27 NF‐κB. Results Compared group, gene microglia significantly exacerbated neurological deficits increased MCAO mice. The loss promoted inflammation by upregulating pro‐inflammatory factors downregulating anti‐inflammatory factors, also enhancing both OGD/R. Furthermore, reduced NF‐κB aforementioned models. Conclusion critical neuroinflammatory regulating NF‐κB, positioning it as target for treatment.

Язык: Английский

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Poliumoside Exhibits Neuroprotective Effects against Cerebral Ischemia-Reperfusion Injury by Relieving Microglia-Mediated Neuronal Damage and Astrocytic Activation

ACS Chemical Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Апрель 28, 2025

Язык: Английский

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Neuroinflammatory Proteins in Huntington’s Disease: Insights into Mechanisms, Diagnosis, and Therapeutic Implications

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(21), С. 11787 - 11787

Опубликована: Ноя. 2, 2024

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by CAG tract expansion in the huntingtin gene (

Язык: Английский

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