Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106885 - 106885
Опубликована: Март 1, 2025
Язык: Английский
Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 168, С. 115653 - 115653
Опубликована: Окт. 7, 2023
The modulation of microglial polarization from the pro-inflammatory M1 to anti-inflammatory M2 phenotype shows promise as a therapeutic strategy for ischemic stroke. Quercetin, natural flavonoid abundant in various plants, possesses anti-inflammatory, anti-apoptotic, and antioxidant properties. Nevertheless, its effect underlying mechanism on microglia/macrophages M1/M2 treatment cerebral ischemia/reperfusion injury (CI/RI) remain poorly explored. In current study, we observed that quercetin ameliorated neurological deficits, reduced infarct volume, decreased number (CD16/32+/Iba1+), enhanced (CD206+/Iba1+) after establishing CI/RI model rats. Subsequent vivo vitro experiments indicated downregulated markers (CD86, iNOS, TNF-α, IL-1β, IL-6) upregulated (CD206, Arg-1, IL-10, TGF-β). Network pharmacology analysis molecular docking revealed PI3K/Akt/NF-κB signaling pathway emerged core pathway. Western blot confirmed phosphorylation PI3K Akt, while alleviating IκBα NF-κB both vitro. However, inhibitor LY294002 reversed effects expression key proteins primary microglia oxygen-glucose deprivation/reoxygenation (OGD/R) Collectively, our findings demonstrate facilitates by modulating CI/RI. These provide novel insights into mechanisms
Язык: Английский
Процитировано
87
Pharmacological Research, Год журнала: 2024, Номер 206, С. 107300 - 107300
Опубликована: Июль 9, 2024
Depression is a serious global mental disorder. Numerous studies have found that depression may be closely related to decreased neurogenesis, neuroinflammation, neurotransmitter imbalance, and synaptic plasticity dysfunction. The pathogenesis of complex involves multiple signal transduction pathways molecular changes. PI3K/AKT pathway an essential signaling in neurons, which widely expressed emotion-related regions the brain. Therefore, play moderating role mood disorders. However, mechanism not been fully described. This review systematically summarized discussed its potential treatment depression. will help development antidepressants.
Язык: Английский
Процитировано
34
Cytokine & Growth Factor Reviews, Год журнала: 2024, Номер 78, С. 105 - 119
Опубликована: Июль 2, 2024
Язык: Английский
Процитировано
31
Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)
Опубликована: Янв. 29, 2024
Microglia is the major contributor of post-stroke neuroinflammation cascade and crucial cellular target for treatment ischemic stroke. Currently, endogenous mechanism underlying microglial activation following stroke remains elusive. Serglycin (SRGN) a proteoglycan expressed in immune cells. Up to now, role SRGN on largely unexplored.
Язык: Английский
Процитировано
18
Journal of Clinical Medicine, Год журнала: 2025, Номер 14(2), С. 386 - 386
Опубликована: Янв. 9, 2025
The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from bloodstream into central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's Parkinson's disease, well ischemic stroke, compromise integrity BBB. This leads to increased permeability infiltration harmful substances, thereby accelerating neurodegeneration. In this review, we explore mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, loss tight junction integrity, in patients with neurodegenerative diseases. We discuss how breakdown contributes neurotoxicity, abnormal accumulation pathological proteins, all which exacerbate neuronal damage facilitate disease progression. Furthermore, potential therapeutic strategies aimed at preserving or restoring function, anti-inflammatory treatments, antioxidant therapies, approaches enhance integrity. Given role neurodegeneration, maintaining its represents promising approach slow prevent progression
Язык: Английский
Процитировано
6
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(19), С. 14771 - 14771
Опубликована: Сен. 30, 2023
The neuroinflammatory response after intracerebral hemorrhage (ICH) causes a large amount of neuronal loss, and inhibiting the inflammatory can improve prognosis. In previous laboratory studies clinical trials, ursolic acid (UA) inhibited response, but whether it be administered to inhibit cerebral is unknown. aim this study was investigate effects hemorrhage. Online databases were used obtain potential therapeutic targets for treatment hemorrhage, possible mechanisms analyzed by KEGG, GO, molecular docking. A rat model established using collagenase, an in vitro constructed adding hemin BV2 cell culture medium. Enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), immunofluorescence, TUNEL staining, calcein/PI staining degree microglial M1 polarization, changes levels factors, activation NF-κB pathway, indicators cellular death treatment. addition, phorbol 12-myristate 13-acetate (PMA) activate pathway verify that exerts its anti-neuroinflammatory regulating NF-κB/NLRP3/GSDMD pathway. Network pharmacology bioinformatics analyses revealed may exert on through multiple pathways. Together, vivo experiments showed polarization significantly reduced p-NF-κB, GSDMD-N, cleaved caspase-1, TNF-α, IL-6, IL-1β, which use PMA. Ursolic inhibits pyroptosis via alleviate responses
Язык: Английский
Процитировано
31
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(19), С. 14848 - 14848
Опубликована: Окт. 3, 2023
Stroke is among the most prevalent causes of disability and second leading cause death worldwide in Western countries [...]
Язык: Английский
Процитировано
26
Translational Stroke Research, Год журнала: 2024, Номер unknown
Опубликована: Май 14, 2024
Abstract Stroke in China is distinguished by its high rates of morbidity, recurrence, disability, and mortality. The ultra-early administration rtPA essential for restoring perfusion acute ischemic stroke, though it concurrently elevates the risk hemorrhagic transformation. High-mobility group box 1 (HMGB1) emerges as a pivotal player neuroinflammation after brain ischemia ischemia–reperfusion. Released passively necrotic cells actively secreted, including direct secretion HMGB1 into extracellular space packaging intracellular vesicles immune cells, glial platelets, endothelial represents prototypical damage-associated molecular pattern (DAMP). It intricately involved pathogenesis atherosclerosis, thromboembolism, detrimental inflammation during early phases stroke. Moreover, significantly contributes to neurovascular remodeling functional recovery later stages. Significantly, mediates transformation facilitating neuroinflammation, directly compromising integrity blood–brain barrier, enhancing MMP9 through interaction with rtPA. As systemic inflammatory factor, also implicated post-stroke depression an elevated stroke-associated pneumonia. role extends influencing polarizing various subtypes cells. This includes mediating excitotoxicity due excitatory amino acids, autophagy, release, NET formation, autocrine trophic pathways. Given multifaceted role, recognized crucial therapeutic target prognostic marker stroke In this review, we summarize structure redox properties, pathways, regulation cell activity, pathophysiological mechanisms hemorrhage HMGB1, which will pave way developing new neuroprotective drugs, reduction expansion thrombolysis time window.
Язык: Английский
Процитировано
18
ACS Nano, Год журнала: 2024, Номер 18(26), С. 16450 - 16467
Опубликована: Июнь 19, 2024
Nanozymes, which can selectively scavenge reactive oxygen species (ROS), have recently emerged as promising candidates for treating ischemic stroke and traumatic brain injury (TBI) in preclinical models. ROS overproduction during the early phase of these diseases leads to oxidative damage, has been a major cause mortality worldwide. However, clinical application ROS-scavenging enzymes is limited by their short vivo half-life inability cross blood-brain barrier. mimic catalytic function natural enzymes, several advantages, including cost-effectiveness, high stability, easy storage. These advantages render them superior disease diagnosis therapeutic interventions. This review highlights recent advancements nanozyme applications TBI, emphasizing potential mitigate detrimental effect overproduction, inflammation, barrier compromise. Therefore, nanozymes represent treatment modality conditions future medical practices.
Язык: Английский
Процитировано
17
Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)
Опубликована: Янв. 21, 2025
Abstract Central nervous system (CNS) injuries, such as ischemic stroke (IS), intracerebral hemorrhage (ICH) and traumatic brain injury (TBI), are a significant global burden. The complex pathophysiology of CNS is comprised primary secondary injury. Inflammatory incited by damage-associated molecular patterns (DAMPs) which signal variety resident cells infiltrating immune cells. Extracellular cold-inducible RNA-binding protein (eCIRP) DAMP acts through multiple non-immune to promote inflammation. Despite the well-established role eCIRP in systemic sterile inflammation, its less elucidated. Recent literature suggests that pleiotropic inflammatory mediator also being evaluated clinical biomarker indicate prognosis injuries. This review provides broad overview injury, with focus on immune-mediated neuroinflammation. We then what known about mechanisms both non-CNS cells, identifying opportunities for further study. explore eCIRP’s potential prognostic marker severity outcome. Next, we provide an eCIRP-targeting therapeutics suggest strategies develop these agents ameliorate Finally, emphasize exploring novel mechanisms, aside from neuroinflammation, critical therapeutic target
Язык: Английский
Процитировано
2