Progress in Neurobiology, Год журнала: 2025, Номер 247, С. 102732 - 102732
Опубликована: Фев. 26, 2025
Язык: Английский
Current Neurology and Neuroscience Reports, Год журнала: 2023, Номер 23(8), С. 407 - 431
Опубликована: Июль 3, 2023
Язык: Английский
Процитировано
138
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
15
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(11), С. 9144 - 9144
Опубликована: Май 23, 2023
Microglia are the resident immune cells of central nervous system that guarantee surveillance and exert also a modulating role on neuronal synaptic development function. Upon injury, microglia get activated modify their morphology acquiring an ameboid phenotype pro- or anti-inflammatory features. The active in blood–brain barrier (BBB) function interaction with different cellular components BBB—endothelial cells, astrocytes pericytes—are described. Here, we report specific crosstalk all BBB cell types focusing particular involvement modulation neuroinflammatory conditions occur conjunction acute event, such as stroke, slow neurodegenerative disease, Alzheimer’s disease. potential to dual role, either protective detrimental, depending disease stages environmental conditioning factors is discussed.
Язык: Английский
Процитировано
31
Pharmacological Research, Год журнала: 2023, Номер 193, С. 106803 - 106803
Опубликована: Май 23, 2023
Although strides have been made, the challenge of preventing and treating ischemic stroke continues to persist globally. For thousands years, natural substances Frankincense Myrrh employed in Chinese Indian medicine address cerebrovascular diseases, with key components 11-keto-β-boswellic acid (KBA) Z-Guggulsterone (Z-GS) being active agents. In this study, synergistic effect underlying mechanism KBA Z-GS on were examined using single-cell transcriptomics. Fourteen cell types identified KBA-Z-GS-treated penumbra, microglia astrocytes account for largest proportion. They further re-clustered into six seven subtypes, respectively. GSVA analysis reflected distinct roles each subtype. Pseudo-time trajectory indicated that Slc1a2 Timp1 core fate transition genes regulated by KBA-Z-GS. addition, KBA-Z-GS synergistically inflammatory reactions cellular metabolism ferroptosis astrocytes. Most notably, we established an innovative drug-gene regulation pattern, divided four categories based pattern. Finally, Spp1 was demonstrated as hub target Taken together, study reveals cerebral ischemia, may be that. Precise drug development targeting offer a potential therapeutic approach stroke.
Язык: Английский
Процитировано
28
CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 29(8), С. 2129 - 2144
Опубликована: Март 13, 2023
Abstract Background Immediately after spinal trauma, immune cells, and proinflammatory cytokines infiltrate the cord disrupt focal microenvironment, which impedes axon regeneration functional recovery. Previous studies have reported that regulatory T cells (Tregs) enter central nervous system exert immunosuppressive effects on microglia during multiple sclerosis stroke. However, whether how Tregs interact with modulate injured microenvironments injury (SCI) remains unknown. Method Regulatory spatiotemporal characteristics were analyzed in a mouse contusion SCI model. Microglia activation status was evaluated by immunostaining RNA sequencing. Cytokine production examined using Luminex. The role of STAT3 Treg–microglia crosstalk investigated transwell isolated primary microglia. Results infiltration peaked day 7 SCI. Treg depletion promoted switch to phenotype. Inflammation‐related genes, such as ApoD , well downstream IL‐6 TNF‐α upregulated Treg‐depleted mice. inhibition involved crosstalk, chemical blockade improved function recovery Conclusion Our results suggest promote alleviating inflammatory reaction via STAT3.
Язык: Английский
Процитировано
25
Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)
Опубликована: Март 21, 2024
Abstract Myeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia–reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates secretion release activates neuroinflammation, aggravating I/R injury. However, cellular sources MPO/HOCl ischemic brain are unclear yet. Whether HOCl could promote remains unknown. In present study, we investigated roles microglia-derived mediating translocation secretion, damage blood-brain barrier (BBB) disruption vitro, under co-culture conditions with microglia BV cells but not single culture conditions, oxygen–glucose deprivation/reoxygenation (OGD/R) significantly increased expression PC12 cells. After were exposed to OGD/R, MPO-containing exosomes derived from BV2 released transferred cells, increasing The promoted aggravated OGD/R-induced apoptosis. vivo, SD rats subjected 2 h middle artery occlusion (MCAO) plus different periods reperfusion. Increased production was observed at reperfusion stage, accomplished enlarged infarct volume, BBB neurological dysfunctions. Treatment MPO inhibitor 4-aminobenzoic hydrazide (4-ABAH) scavenger taurine reversed those changes. colocalized cytoplasm HMGB1, which blocked by rat I/R-injured brain. We finally performed a clinical investigation found that plasma concentration positively correlated volume deficit scores stroke patients. Taken together, conclude ischemia/hypoxia activate transfer adjacent for production; Subsequently, mediate aggravates Furthermore, level be novel biomarker indexing
Язык: Английский
Процитировано
13
Molecular Brain, Год журнала: 2025, Номер 18(1)
Опубликована: Фев. 17, 2025
Abstract Cardiac arrest (CA) is one of the most common illnesses worldwide. Post-CA brain injury (PCABI) a major cause death and poor recovery in CA patients current treatments are not very effective. The microbiome-gut-brain axis has been found to significantly affect ischemia injury. Furthermore, ischemic stroke patients, short-chain fatty acids (SCFA), especially sodium butyrate (SB), have observed promote neuroprotective effects by modulating inflammatory response microglial polarization cortex. However, precise mechanism SB on CA-induced remains elusive. Therefore, this research study established an oxygen–glucose deprivation reoxygenation (OGD/R) model using BV-2 HT22 cells simulate cerebral ischemia/reperfusion vitro potassium chloride-induced mouse mimic vivo. data revealed that markedly improved neurological scores reduced neuronal apoptosis. Moreover, it M1 microglia neuroinflammation mice. In addition, increased intestinal integrity alleviated systemic inflammation. 16S rDNA sequencing analysis indicated intervention mitigated gut microbiota dysbiosis SCFA depletion. It was also mice’s OGD/R-exposed BV2 had substantially levels MyD88, phosphorylated NF-κB p65, TLR4 proteins, which were after treatment. summary, can protect against ischemia–reperfusion controlling inhibit inflammation via TLR4/MyD88/NF-κB pathway.
Язык: Английский
Процитировано
1
Biomolecules, Год журнала: 2023, Номер 13(3), С. 571 - 571
Опубликована: Март 21, 2023
Stroke causes varying degrees of neurological deficits, leading to corresponding dysfunctions. There are different therapeutic principles for each stage pathological development. Neuroprotection is the main treatment in acute phase, and functional recovery becomes primary subacute chronic phases. Neuroplasticity considered basis restoration rehabilitation after stroke, including remodeling dendrites dendritic spines, axonal sprouting, myelin regeneration, synapse shaping, neurogenesis. Spatiotemporal development affects spontaneous rewiring neural circuits brain networks. Microglia resident immune cells that contribute homeostasis under physiological conditions. activated immediately phenotypic polarization changes phagocytic function crucial regulating focal global inflammation recovery. We have previously shown neuroplasticity spatiotemporally consistent with microglial activation, suggesting microglia may a profound impact on stroke be key target post-stroke rehabilitation. In this review, we explore as well functions mechanisms polarization, phagocytosis. This followed by summary microglia-targeted rehabilitative interventions influence promote
Язык: Английский
Процитировано
16
Acta Pharmacologica Sinica, Год журнала: 2024, Номер 45(7), С. 1349 - 1365
Опубликована: Март 19, 2024
Язык: Английский
Процитировано
7
Neuroprotection/Neuroprotection (Chichester, England. Print), Год журнала: 2024, Номер 2(1), С. 4 - 15
Опубликована: Март 1, 2024
Abstract Stem cell‐based therapies and extracellular vesicle (EV) treatment have demonstrated significant potential for neuroprotection against ischemic stroke. Although the neuroprotective mechanisms are not yet fully understood, targeting microglia is central to promoting neuroprotection. Microglia resident immune cells of nervous system. These crucial in pathogenesis They respond rapidly site injury by releasing pro‐inflammatory cytokines, phagocytizing dead debris, recruiting peripheral area. these responses essential clearing damage initiating tissue repair, excessive or prolonged microglial activation can exacerbate brain injury, leading secondary neuroinflammation neurodegeneration. Moreover, exhibit a dynamic range states with so‐called M1 M2 anti‐inflammatory phenotypes, representing two ends spectrum. The delivery both EVs stem modulates activation, suppressing genes, influencing expression transcription factors, altering receptor expression, ultimately contributing findings underscore importance understanding complex role development effective strategies reduce effects In this review, we examine current state knowledge regarding stroke, including their molecular cellular mechanisms, states, interactions other cells. We also discuss multifaceted contributions cell‐ EV‐based during an stroke provide comprehensive functions implications therapies.
Язык: Английский
Процитировано
7