Selective deletion of interleukin-1 alpha in microglia does not modify acute outcome but regulates neurorepair processes after experimental ischemic stroke DOI Open Access
Eloïse Lemarchand, Alba Grayston, Raymond Wong

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 21, 2024

Abstract Inflammation is a key contributor to stroke pathogenesis and exacerbates brain damage leading poor outcome. Interleukin-1 (IL-1) an important regulator of post-stroke inflammation, blocking its actions beneficial in pre-clinical models safe the clinical setting. However, distinct roles two major IL-1 receptor type 1 agonists, IL-1α IL-1β, specific role ischemic remain largely unknown. Here we show that IL-1β have different spatio-temporal expression profiles after experimental stroke, with early microglial (4 h) delayed infiltrated neutrophils small subset (24-72 h). We examined for first time microglial-derived permanent transient through microglial-specific tamoxifen-inducible Cre-loxP-mediated recombination. Microglial deletion did not influence acute damage, cerebral blood flow, expression, neutrophil infiltration, nor endothelial activation stroke. knock out (KO) mice showed reduced peri-infarct vessel density reactive astrogliosis at 14 days post-stroke, alongside long-term impaired functional recovery. Our study identifies critical on neurorepair recovery highlighting importance targeting mechanisms injury develop more effective therapies.

Language: Английский

Neuroserpin and Extracellular Vesicles in Ischemic Stroke: Partners in Neuroprotection? DOI Creative Commons
Santra Brenna, Markus Glatzel, Tim Magnus

et al.

Aging and Disease, Journal Year: 2024, Volume and Issue: 15(5), P. 2191 - 2191

Published: Jan. 1, 2024

Ischemic stroke represents a significant global health challenge, often resulting in death or long-term disability, particularly among the elderly, where advancing age stands as most unmodifiable risk factor. Arising from blockage of brain-feeding artery, only therapies available to date aim at removing blood clot restore cerebral flow and rescue neuronal cells death. The prevailing treatment approach involves thrombolysis by administration recombinant tissue plasminogen activator (tPA), albeit with critical time constraint. Timely intervention is imperative, given that delayed increases tPA leakage into brain parenchyma, causing harmful effects. Strategies preserve tPA's vascular benefits while shielding its toxicity have been explored. Notably, administering neuroserpin (Ns), brain-specific inhibitor, one such approach. Following ischemic stroke, Ns levels rise correlate favorable post-stroke outcomes. Studies rodent models focal ischemia demonstrated beneficial effects administration. maintains blood-brain barrier (BBB) integrity, reducing volume. Conversely, Ns-deficient animals exhibit larger injury, increased BBB permeability enhanced microglia activation. Furthermore, extends therapeutic window for intervention, underscoring potential management. Remarkably, our investigation reveals presence within extracellular vesicles (EVs), small membrane-surrounded particles released all intercellular communication. EVs influence disease outcome following through cargo transfer between cells. Clarifying role containing NS could open up urgently needed novel approaches improve post-ischemic outcome.

Language: Английский

Citations

1
Integrative transcriptomic analysis reveals Cd72 as a novel pro-inflammatory factor in microglia following experimental ischemic stroke DOI

Haojie Ding,

Xuan Shi,

Junwei Ma

et al.

Experimental Neurology, Journal Year: 2024, Volume and Issue: 382, P. 114974 - 114974

Published: Sept. 24, 2024

Language: Английский

Citations

1
Ion channels in macrophages: Implications for disease progression DOI
Li Xu, Yuzhe Du,

Chunlei Yu

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 144, P. 113628 - 113628

Published: Nov. 19, 2024

Language: Английский

Citations

1
A Novel Compound Ligusticum Cycloprolactam Alleviates Neuroinflammation After Ischemic Stroke via the FPR1/NLRP3 Signaling Axis DOI Creative Commons
Juan Gao,

Gang Su,

Jifei Liu

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(12)

Published: Dec. 1, 2024

ABSTRACT Background Microglia/macrophages, as pivotal immune cells in the central nervous system (CNS), play a critical role neuroinflammation associated with ischemic brain injury. Targeting their activation through pharmacological interventions represents promising strategy to alleviate neurological deficits, thereby harboring significant implications for prevention and treatment of stroke. Ligusticum cycloprolactam (LIGc), novel monomeric derivative traditional Chinese medicine, has shown potential therapeutic agent; however, its specific cerebral injury remains unclear. Methods In vitro experiments utilized lipopolysaccharide (LPS)‐induced inflammation models RAW264.7 primary mouse microglia. vivo studies employed LPS‐induced mice transient middle artery occlusion (tMCAO) model evaluate impact LIGc on microglia/macrophage phenotypic alterations. Further elucidation molecular mechanisms underlying these effects was achieved RNA‐Seq analyses. Results exhibited capacity attenuate production pro‐inflammatory markers macrophages microglia, facilitating transition an anti‐inflammatory phenotype. tMCAO, ameliorated pathological behaviors deficits while mitigating inflammation. RNA‐seq analyses revealed formyl peptide receptor 1 (FPR1) mediator LIGc's effects. Specifically, FPR1 enhances phenotype microglia/macrophages inhibits response by upregulating NLR family pyrin domain protein 3 (NLRP3) inflammasomes, thus aggravating inflammatory processes. Conversely, exerts downregulating FPR1/NLRP3 signaling axis. Furthermore, overexpression or NLRP3 agonists reversed observed this study. Conclusion Our findings suggest that holds promise improving modulation polarization. Mechanistically, attenuates promotes targeting pathway, ultimately reducing responses damage.

Language: Английский

Citations

1
Selective deletion of interleukin-1 alpha in microglia does not modify acute outcome but regulates neurorepair processes after experimental ischemic stroke DOI Open Access
Eloïse Lemarchand, Alba Grayston, Raymond Wong

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 21, 2024

Abstract Inflammation is a key contributor to stroke pathogenesis and exacerbates brain damage leading poor outcome. Interleukin-1 (IL-1) an important regulator of post-stroke inflammation, blocking its actions beneficial in pre-clinical models safe the clinical setting. However, distinct roles two major IL-1 receptor type 1 agonists, IL-1α IL-1β, specific role ischemic remain largely unknown. Here we show that IL-1β have different spatio-temporal expression profiles after experimental stroke, with early microglial (4 h) delayed infiltrated neutrophils small subset (24-72 h). We examined for first time microglial-derived permanent transient through microglial-specific tamoxifen-inducible Cre-loxP-mediated recombination. Microglial deletion did not influence acute damage, cerebral blood flow, expression, neutrophil infiltration, nor endothelial activation stroke. knock out (KO) mice showed reduced peri-infarct vessel density reactive astrogliosis at 14 days post-stroke, alongside long-term impaired functional recovery. Our study identifies critical on neurorepair recovery highlighting importance targeting mechanisms injury develop more effective therapies.

Language: Английский

Citations

0