A new perspective on the regulation of neuroinflammation in intracerebral hemorrhage: mechanisms of NLRP3 inflammasome activation and therapeutic strategies

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 27, 2025

Intracerebral hemorrhage (ICH), a specific subtype within the spectrum of stroke disorders, is characterized by its high mortality and significant risk long-term disability. The initiation progression neuroinflammation play central critical role in pathophysiology ICH. NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, protein complex involved initiating inflammation, focus this article. Microglia astrocytes roles inflammatory damage process associated with neuroinflammation. NLRP3 inflammasome expressed both types glial cells, activation drives these cells toward pro-inflammatory phenotype, which exacerbates brain. However, regulatory relationship between two cell remains to be explored. Targeting inflammasomes microglia or may provide an effective approach mitigate following This article first provides overview composition mechanisms inflammasome. Subsequently, it summarizes recent research findings on novel signaling pathways that regulate activity. Finally, we reviewed progress inhibitors, highlighting clinical translation potential certain candidates. These inhibitors hold promise as innovative strategies for managing inflammation

Language: Английский

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Animal-based approaches to understanding neuroglia physiology in vitro and in vivo

Handbook of clinical neurology, Journal Year: 2025, Volume and Issue: unknown, P. 229 - 263

Published: Jan. 1, 2025

Language: Английский

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PT109B, a Multikinase Inhibitor, Converts Astrocytes into Dopaminergic Neurons and Alleviates Parkinson's Disease in Mice

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Background Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons (DANs), leading to motor dysfunction, while current treatments fail restore neuronal loss. Reprogramming astrocytes into induced DANs small molecules offers a promising therapeutic strategy, but existing methods face challenges including low efficiency and complex mechanisms. PT109B, novel multi-kinase inhibitor, has demonstrated neurogenic synaptogenic potential in neural progenitor cells, as well glioblastoma differentiation capacity, yet its ability directly convert functional effects PD remain unclear. Methods Primary rat midbrain were treated with 10 µM PT109B evaluate reprogramming via immunofluorescence (GFAP, MAP2, NeuN, TH, DAT) electrophysiological recordings. RNA sequencing was performed at 1.5, 3, 6 hours post-treatment assess transcriptional changes. In vivo, (100 mg/kg) administered orally for 12 weeks 6-OHDA-induced mice, labeled AAV5-GFAP-EGFP. Behavioral tests (apomorphine rotation, pole test, rotarod, open field), retrograde tracing, immunohistochemistry conducted effects. Results initiated astrocyte-to-neuron conversion early 3 hours, yielding 20% TH⁺ 2 vitro, mature properties action potentials, sodium currents sustained dopamine release (> months). Mechanistically, drove this through cell cycle arrest, astrocytic activation, upregulation key basic Helix-Loop-Helix (b-HLH) transcription factors (NeuroD1, Ascl1, Ngn2). In vivo, oral administration mouse model exhibited significant efficacy striatum, improved functions. Conclusions efficiently converts rapid ameliorates PD-related pathology deficits, presenting safe effective single-molecule strategy PD.

Language: Английский

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Progress in Research on TLR4-Mediated Inflammatory Response Mechanisms in Brain Injury after Subarachnoid Hemorrhage

Cells, Journal Year: 2022, Volume and Issue: 11(23), P. 3781 - 3781

Published: Nov. 26, 2022

Subarachnoid hemorrhage (SAH) is one of the common clinical neurological emergencies. Its incidence accounts for about 5-9% cerebral stroke patients. Even surviving patients often suffer from severe adverse prognoses such as hemiplegia, aphasia, cognitive dysfunction and even death. Inflammatory response plays an important role during early nerve injury in SAH. Toll-like receptors (TLRs), pattern recognition receptors, are components body's innate immune system, they usually activated by damage-associated molecular molecules. Studies have shown that with TLR 4 essential member TLRs family, inflammatory transduction pathway mediated it a vital brain after After SAH occurrence, large amounts blood enter subarachnoid space. This can produce massive molecules bind to TLR4, which activates causes injury, thus resulting serious prognoses. In this paper, process research on TLR4-mediated mechanism was reviewed provide new thought treatment.

Language: Английский

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Serum Homer1 is a Novel Biomarker for Predicting the Clinical Outcomes of Acute Ischemic Stroke Patients

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 1337 - 1347

Published: Feb. 1, 2024

Purpose: We aim to explore the relationship between Homer1 and outcomes of AIS patients at 3 months. Patients Methods: This prospective cohort study was conducted from May 2022 March 2023. In this study, we investigated association serum levels by enzyme-linked immunosorbent assay admission functional months after AIS. Results: Overall, 89 (48 good 41 poor outcomes) 83 healthy controls were included. The median level with significantly higher than that (39.33 vs 33.15, P < 0.001). Serum positively correlated severity (r = 0.488, optimal cutoff as an indicator for auxiliary diagnosis 35.07 pg/mL, a sensitivity 75.0% specificity 92.7% (AUC 0.837; 95% CI [0.744– 0.907]; 0 odds ratio MRS > 2 predicted 1.665 (1.306– 2.122; Conclusion: concentrations have high predictive value neurobehavioral acute ischemic stroke. Higher (> pg/mL) associated post-stroke. Keywords: Homer1, stroke, biomarker,

Language: Английский

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