Unravelling the nexus of stroke and dementia: Deciphering the role of secondary neurodegeneration in orchestrating cognitive decline DOI Creative Commons
Shannon M. Stuckey, Rebecca J. Hood, Lin Kooi Ong

et al.

Neuroprotection/Neuroprotection (Chichester, England. Print), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract Stroke is the leading cause of acquired disability. The development acute ischemic stroke treatments, such as mechanical thrombectomy and tissue plasminogen activator, has resulted in more patients surviving initial insult. However, long‐term complications, post‐stroke cognitive impairment (PSCI) dementia (PSD), are at an all‐time high. Notably, 80% survivors suffer from impairment, a history doubles patient's lifetime risk developing dementia. A combination greater life expectancy, increase number strokes young individuals, improved survival have inherently increased years living post‐stroke, highlighting critical need to understand effects stroke, including how pathological changes brain might give rise functional behavioral survivors. Even with this PSCI PSD survivors, understanding itself develops into these conditions remains incomplete. Recently, secondary neurodegeneration (SND) following been linked PSD. SND degeneration regions outside original site. Degeneration sites thought arise due diaschisis infarct core; however, observation pathology multiple without direct connectivity suggests that likely complex. Moreover, hallmarks dementia, deposition neurodegenerative proteins iron, cell death, inflammation blood–brain barrier alterations, all found thalamus, hippocampus, basal ganglia, amygdala prefrontal cortex stroke. Hence, review, we present current context outline remote anatomical molecular may drive conditions.

Language: Английский

Therapeutic strategies targeting the NLRP3‑mediated inflammatory response and pyroptosis in cerebral ischemia/reperfusion injury (Review) DOI Creative Commons
Wanli Duan, Xuejie Wang, Yaping Ma

et al.

Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 29(3)

Published: Jan. 22, 2024

Ischemic stroke poses a major threat to human health. Therefore, the molecular mechanisms of cerebral ischemia/reperfusion injury (CIRI) need be further clarified, and associated treatment approaches require exploration. The NOD‑like receptor thermal protein domain 3 (NLRP3) inflammasome serves an important role in causing CIRI, its activation exacerbates underlying injury. Activation NLRP3 triggers maturation production inflammatory molecules IL‑1β IL‑18, as well gasdermin‑D‑mediated pyroptosis CIRI damage. Thus, may viable target for CIRI. In present review, intense response induced by are discussed, therapeutic strategies that NLRP3‑mediated summarized. At present, certain drugs have already been studied, highlighting future perspectives.

Language: Английский

Citations

7
T cell-mediated skin-brain axis: Bridging the gap between psoriasis and psychiatric comorbidities DOI

Juexi Yang,

Zhang Song,

Qixuan Wu

et al.

Journal of Autoimmunity, Journal Year: 2024, Volume and Issue: 144, P. 103176 - 103176

Published: Feb. 15, 2024

Language: Английский

Citations

7
ATP-sensitive potassium channel opener, Nicorandil, inhibits NF-κB/AIM2/GSDMD pathway activation to protect against neuroinflammation in ischemic stroke DOI Creative Commons

Chenming Zhao,

Xiaojuan Fu,

Zhuoying Yang

et al.

Neurochemistry International, Journal Year: 2024, Volume and Issue: 179, P. 105810 - 105810

Published: July 26, 2024

The absent in melanoma 2 (AIM2) inflammasome contributes to ischemic brain injury by inducing cell pyroptosis and inflammatory responses. Our research group has previously demonstrated that ATP-sensitive potassium channels (KATP channels) openers can modulate neuronal synaptic plasticity post-ischemic stroke for neuroprotection. However, the specific mechanisms of KATP response following remain unclear. Here, we assessed cellular damage observing changes BV-2 morphology viability. 2,3,5-Triphenyl tetrazolium chloride (TTC) staining, mNSS scoring, Nissl TdT-mediated dUTP nick end labeling (TUNEL) staining were used evaluate behavioral deficits, severity, mice subjected middle cerebral artery occlusion (MCAO). Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, immunofluorescence, enzyme-linked immunosorbent assay (ELISA) measure nuclear factor-kappaB (NF-κB) activation vivo vitro. We observed AIM2 protein expression was upregulated localized within cytoplasm cells. Notably, low-dose Nicorandil treatment reduced cytokine secretion pyroptosis-related expression, including AIM2, cleaved cysteinyl aspartate-specific protease-1 (cleaved caspase-1), Gasdermin D N-terminal (GSDMD-NT). Further investigations revealed channel inhibitor 5-HD p-NF-κB p65, NF-κB p-IκBα reversing Nicorandil's neuroprotective effect vivo. In summary, our results suggest may serve as a potential therapeutic option stroke. Targeting represents effective strategies inhibiting neuroinflammation.

Language: Английский

Citations

6
Astrocyte-derived exosomal miR-378a-5p mitigates cerebral ischemic neuroinflammation by modulating NLRP3-mediated pyroptosis DOI Creative Commons
Ruiting Sun,

Wenxin Liao,

Ting Lang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 8, 2024

This study aimed to investigate the regulatory role of astrocyte-derived exosomes and their microRNAs (miRNAs) in modulating neuronal pyroptosis during cerebral ischemia.

Language: Английский

Citations

6
To re-examine the intersection of microglial activation and neuroinflammation in neurodegenerative diseases from the perspective of pyroptosis DOI Creative Commons
Yuan Li, Yingjie Li, Zhaoqiong Zhu

et al.

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Nov. 9, 2023

Neurodegenerative diseases (NDs), such as Alzheimer’s disease, Parkinson’s Huntington’s and motor neuron are characterized by neuronal damage dysfunction. NDs considered to be a multifactorial disease with diverse etiologies (immune, inflammatory, aging, genetic, etc.) complex pathophysiological processes. Previous studies have found that neuroinflammation typical microglial activation important mechanisms of NDs, leading neurological dysfunction progression. Pyroptosis is new mode involved in this process. As form programmed cell death, pyroptosis the expansion cells until membrane bursts, resulting release contents activates strong inflammatory response promotes accelerating abnormal activation. In case, abnormally activated microglia various pro-inflammatory factors, occurrence exacerbating both pyroptosis, thus forming vicious cycle. The recognition association between activation, well neuroinflammation, significant importance understanding pathogenesis providing targets strategies for their prevention treatment.

Language: Английский

Citations

13
Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke DOI Creative Commons

Shuai Feng,

Juanji Li, Tingting Liu

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(2), P. 491 - 502

Published: April 16, 2024

JOURNAL/nrgr/04.03/01300535-202502000-00027/figure1/v/2024-05-28T214302Z/r/image-tiff Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury. Low-density lipoprotein receptor, classic cholesterol regulatory has been found to inhibit NLR family pyrin domain containing protein 3 (NLRP3) inflammasome activation in neurons following ischemic stroke and suppress microglia individuals with Alzheimer's disease. However, little is known about effects low-density receptor on astrocytic stroke. To address this issue present study, we examined mechanisms by which regulates polarization models. First, expression via immunofluorescence staining western blotting analysis. We observed significant downregulation middle artery occlusion reperfusion oxygen-glucose deprivation/reoxygenation. Second, induced astrocyte-specific overexpression using adeno-associated virus. improved neurological outcomes mice reversed neurotoxic create neuroprotective phenotype. Finally, that inhibited NLRP3 deprivation/reoxygenation injured addition nigericin, an agonist, restored astrocyte These findings suggest could NLRP3-meidiated increasing might represent novel strategy treating

Language: Английский

Citations

5
Harnessing Pyroptosis for Lung Cancer Therapy: The Impact of NLRP3 Inflammasome Activation DOI
Rajiv Dahiya, Vijaykumar Sutariya, Sheeba Varghese Gupta

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 260, P. 155444 - 155444

Published: Aug. 1, 2024

Language: Английский

Citations

4
Astragalus mongholicus and Scutellaria baicalensis Extracts Mixture Target Pyroptosis in Ischemic Stroke via the NLRP3 Pathway DOI Open Access

Geon Ko,

Jinho Kim, Yong‐Ki Hong

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 501 - 501

Published: Jan. 9, 2025

Ischemic stroke, caused by blocked cerebral blood flow, requires prompt intervention to prevent severe motor and cognitive impairments. Despite extensive drug development efforts, the failure rate of clinical trials remains high, highlighting need for novel therapeutic approaches. This study investigated potential a natural herbal extract mixture Astragalus mongholicus Bunge (AM) Scutellaria baicalensis Georgi (SB), traditionally used in Eastern Asian medicine (EAHM) ischemic stroke treatment. Using transient middle artery occlusion (tMCAO) photothrombotic (PTB) mouse models, oral administration AM-SB was evaluated during both acute chronic phases. Results showed that significantly reduced infarction volume, inflammation (IL-1β, TNF-α), pyroptosis-related markers (NLRP3, GSDMD, ASC, Caspase-1), while decreasing gliosis improving metabolites. Behavioral assessments revealed early sustained enhanced functions, as measured mNSS, Rotarod, Novel Object Recognition, Passive Avoidance tests. These findings suggest is promising alternative therapy management.

Language: Английский

Citations

0
Genistein-3'-sodium sulfonate suppresses NLRP3-mediated cell pyroptosis after cerebral ischemia DOI
Yunling Yu, Xinglan Liao,

Kewei Xing

et al.

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(1)

Published: Jan. 14, 2025

Language: Английский

Citations

0
Atomized Neutrophil Membrane-coated MOF Nanoparticles for Direct Delivery of Dexamethasone for Severe Pneumonia DOI Creative Commons

Yixiao Yang,

Lizhen Yan,

Han Zhang

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 22, 2025

Background: Dexamethasone has proven life-saving in severe acute respiratory syndrome (SARS) and COVID-19 cases. However, its systemic administration is accompanied by serious side effects. Inhalation delivery of dexamethasone (Dex) faces challenges such as low lung deposition, brief residence the tract, pulmonary mucus barrier, limiting clinical use. Neutrophil cell membrane-derived nanovesicles, with their ability to specifically target hyper-activated immune cells excellent permeability, emerge a promising carrier for inhalation therapy. Methods: We designed novel UiO66 metal-organic framework nanoparticle loaded Dex coated neutrophil membranes (UiO66-Dex@NMP) targeted therapy pneumonia. This was achieved loading into pores subsequently coating functionalization. Results: Drug release experiments revealed UiO66-Dex@NMP exhibit favorable sustained-release properties. Additionally, demonstrated targeting capabilities both vitro vivo. In mouse model lipopolysaccharide (LPS)-induced pneumonia, significantly reduced inflammation compared control administered via inhalation. Histopathological analysis further confirmed UiO66-Dex@NMP’s alleviate tissue damage. Conclusions: represents safe inhaled Dex, offering valuable insights management diseases, including

Language: Английский

Citations

0