Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approaches

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

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Primary microglia cell cultures in translational research: Strengths and limitations

Journal of Biotechnology, Год журнала: 2024, Номер 386, С. 10 - 18

Опубликована: Март 20, 2024

Microglia are the resident macrophages in central nervous system, accounting for 10-15% of cell mass brain. Next to their physiological role development, monitoring neuronal function and maintenance homeostasis, microglia crucial brain's immune defense. Brain injury chronic neurological disorders associated with neuroinflammation, which activation is a element. acquire wide spectrum states diseased or injured brain, some neurotoxic. The investigation (patho)physiology therapeutic interventions targeting neuroinflammation substantial challenge. In addition vivo approaches, application vitro model systems has gained significant ground essential complement work. Primary cultures have proved be useful tool. offered opportunity explore mechanistic, molecular elements activation, secretome, efficacy treatments against neuroinflammation. As all systems, primary distinct strengths limitations weighed when experiments designed data interpreted. Here, we set out provide succinct overview advantages pitfalls use cultures, instructs refinement further development this technique remain toolbox researchers. Since there no conclusive therapy combat neurotoxicity linked acute brain neurodegenerative disorders, these research tools opportunities.

Язык: Английский

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Neural Stem Cell-Derived Small Extracellular Vesicles: key Players in Ischemic Stroke Therapy – A Comprehensive Literature Review

International Journal of Nanomedicine, Год журнала: 2024, Номер Volume 19, С. 4279 - 4295

Опубликована: Май 1, 2024

Ischemic stroke, being a prominent contributor to global disability and mortality, lacks an efficacious therapeutic approach in current clinical settings. Neural stem cells (NSCs) are type of cell that only found inside the nervous system. These can differentiate into various kinds cells, potentially regenerating or restoring neural networks within areas brain have been destroyed. This review begins by providing introduction existing approaches for ischemic followed examination promise limits associated with utilization NSCs treatment stroke. Subsequently, comprehensive overview was conducted synthesize literature on underlying processes cell-derived small extracellular vesicles (NSC-sEVs) transplantation therapy context mechanisms encompass neuroprotection, inflammatory response suppression, endogenous nerve vascular regeneration facilitation. Nevertheless, translation NSC-sEVs is hindered challenges such as inadequate targeting efficacy insufficient content loading. In light these limitations, we compiled advancements utilizing modified treating stroke based methods vesicle modification. conclusion, examining NSC-sEVs-based anticipated be both fundamental applied investigations about

Язык: Английский

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The emerging role of 12/15-lipoxygenase in ischemic stroke

Brain Research Bulletin, Год журнала: 2025, Номер unknown, С. 111194 - 111194

Опубликована: Янв. 1, 2025

The arachidonic acid metabolic pathway is a classic inflammatory pathway. 12/15-lipoxygenase (LOX), member of the lipoxygenase family that metabolizes acid, has been implicated in pathogenesis numerous central nervous system (CNS) diseases. Ischemic stroke devastating disease which occlusion cerebral arteries leads to series pathophysiological changes brain tissue, triggering an cascade within results neuroinflammation. Prior research shown 12/15-LOX levels are elevated following stroke. In this review, we elaborate on key pathological mechanisms unfold ischemic stroke, including neuroinflammation, oxidative stress, neuronal apoptosis, and blood-brain barrier disruption, present evidence demonstrating inhibition could be used treat through various avenues. Furthermore, list currently available inhibitors preclinical or clinical applications, offering novel insights for early diagnosis, prognosis evaluation, targeted therapy neurological

Язык: Английский

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Lipid droplets in central nervous system and functional profiles of brain cells containing lipid droplets in various diseases

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Янв. 13, 2025

Lipid droplets (LDs), serving as the convergence point of energy metabolism and multiple signaling pathways, have garnered increasing attention in recent years. Different cell types within central nervous system (CNS) can regulate to generate or degrade LDs response diverse pathological stimuli. This article provides a comprehensive review on composition CNS, their generation degradation processes, interaction mechanisms with mitochondria, distribution among different types, roles played by these cells-particularly microglia astrocytes-in various prevalent neurological disorders. Additionally, we also emphasize paradoxical role post-cerebral ischemia inflammation explore potential underlying mechanisms, aiming identify novel therapeutic targets for this disease.

Язык: Английский

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Research Progress on the Treatment of Ischemic Stroke by Regulating the Sonic Hedgehog Signaling Pathway with Traditional Chinese Medicine

Journal of Contemporary Medical Practice, Год журнала: 2025, Номер 7(1), С. 180 - 185

Опубликована: Янв. 31, 2025

Ischemic stroke (IS) is a series of pathological damages caused by the interruption local cerebral blood flow. Its pathogenesis extremely complex, involving multiple signaling pathways. Among them, Sonic Hedgehog (Shh) pathway has become research hotspot in recent years. IS falls into category "apoplexy". Apoplexy also known as stroke. Traditional Chinese medicine (TCM) long history treating apoplexy. The comprehensive treatment methods TCM mainly focus on syndrome differentiation and treatment. According to changes syndromes different periods apoplexy, carried out according syndrome. herbal inexpensive targets action. Based above background, this study investigates how alleviates damage regulating Shh pathway, points its shortcomings, providing favorable conditions for subsequent research.

Язык: Английский

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ADAR1 Promotes NUPR1 A-to-I RNA Editing to Exacerbate Ischemic Brain Injury by Microglia Mediated Neuroinflammation

NeuroMolecular Medicine, Год журнала: 2025, Номер 27(1)

Опубликована: Фев. 26, 2025

Язык: Английский

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A dual role for pleiotrophin in modulating inflammation and myelination in the presence of chondroitin sulfate proteoglycans after nervous system injury

Frontiers in Cellular Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Фев. 27, 2025

Chondroitin sulfate proteoglycans (CSPGs), key components of the extracellular matrix and glial scar that forms around central nervous system (CNS) injuries, are recognized for hindering neuronal regeneration. We previously demonstrated potential pleiotrophin (PTN) to induce neurite outgrowth even in presence inhibitory CSPGs. The effects PTN on microglia oligodendrocytes not well described. Here, we examined how administration alters differentiation oligodendrocyte precursor cells (OPCs) into mature CSPGs using vitro cell culture model. Moreover, explored inflammatory activity with without stimulation (IFN-γ) a CSPG-rich environment. data showed CSPG inhibited OPCs oligodendrocytes. induced dose-dependent oligodendrocytes, an optimal effect at 10 nM PTN. modified immunological response CSPGs, reduced proinflammatory was further by administration, contrast increased release metalloproteinases (MMP 9). However, when IFN-γ-activated were treated PTN, signaling stimulated higher concentrations (10 100 nM). Overall, our results indicate can overcome modulate inflammation mediated from microglia. Collectively, these findings demonstrate effectively counteract while also modulating microglial responses reduce increase MMP-9 release. Thus, has great improve remyelination neuroprotective strategies treatment demyelinating diseases or any injury.

Язык: Английский

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Mechanisms of astrocytic and microglial purinergic signaling in homeostatic regulation and implications for neurological disease

Exploration of neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Purinergic signaling, mediated by ATP and adenosine receptors, plays a crucial role in cellular communication homeostasis within the central nervous system (CNS), particularly regulating synaptic activity, glial cell functions, neuroplasticity. Glial cells, including astrocytes microglia, contribute to both short-term processes, such as neurotransmission neuroinflammation, long-term remodeling, tissue repair, behavioral adaptation. Dysregulation of purinergic signaling these cells has been implicated pathogenesis various neurodegenerative neuropsychiatric disorders. This article explores evolving concept synapse, highlighting active modulation emphasizing significance function responses conditions injury neurotoxicity. Specifically, it examines roles receptors—such P2X4, P2X7, P2Y1, P2Y12—in mediating key astrocytic microglial phagocytosis, plasticity, neuronal damage. Furthermore, discusses involvement receptors neurological disorders epilepsy, Alzheimer’s disease, Parkinson’s multiple sclerosis, ischemic stroke, Rett syndrome, autism spectrum disorder, well potential therapeutic strategies targeting mitigate inflammation, promote improve clinical outcomes.

Язык: Английский

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Microglial Annexin A3 Downregulation Alleviates Ischemic Injury by Inhibiting NF-κB/NLRP3-mediated Inflammation

Inflammation, Год журнала: 2025, Номер unknown

Опубликована: Март 15, 2025

Microglial inflammation is a hallmark of ischemic stroke. Annexin A3 (ANXA3) expressed in microglia and plays detrimental role However, the ANXA3 microglial after stroke unclear. In this study, an model was established mice via middle cerebral artery occlusion (MCAO). The adeno-associated virus shANXA3 (AAV-shANXA3) injected into ipsilateral cortex lesion, infarction volume, neurological score, neuronal injury were examined. Moreover, primary transfected with lentivirus (LV-shANXA3) subjected to oxygen–glucose deprivation (OGD). Neuron viability lactose dehydrogenase (LDH) levels neurons cocultured analyzed. Additionally, activation ANXA3, p-NF-κB, NLRP3 downstream proteins inflammasome (cleaved caspase-1, N-GSDMD IL-1β) expression measured. We found that increased knockdown reduced mitigated deficits, alleviated injuries. ameliorated p-NF-κB inhibited signaling. Furthermore, upregulation resulted decreased IκBα levels, whereas downregulation levels. Notably, blocked neuroprotective effects AAV-shANXA3 against injury. conclusion, alleviates by inhibiting NF-κB/NLRP3-mediated inflammation, which indicates may be potential therapeutic target for

Язык: Английский

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