Mailuo Shutong pills inhibit neuroinflammation by regulating glucose metabolism disorders to protect mice from cerebral ischemia-reperfusion injury

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 335, P. 118621 - 118621

Published: July 24, 2024

Language: Английский

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Depletion of Arg1-Positive Microglia/Macrophages Exacerbates Cerebral Ischemic Damage by Facilitating the Inflammatory Response

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 13055 - 13055

Published: Oct. 27, 2022

Stroke is a serious worldwide disease that causes death and disability, more than 80% of which ischemic stroke. The expression arginase 1 (Arg1), key player in regulating nitrogen homeostasis, altered the peripheral circulation after Growing evidence indicates stroke also induces upregulated Arg1 central nervous system, especially activated microglia macrophages. This implies may affect progression by modulating cerebral immune response. To investigate effect Arg1+ microglia/macrophages on stroke, we selectively eliminated mannosylated clodronate liposomes (MCLs) investigated their effects behavior, neurological deficits, inflammatory responses mice More half cells, mainly microglia/macrophages, were depleted MCLs administration, resulting significant deterioration motility mice. After elimination infarct volume expanded neuronal degenerative lesions intensified. Meanwhile, absence significantly increased production pro-inflammatory cytokines suppressed anti-inflammatory factors, thus profoundly altering microenvironment at lesion site. Taken together, our data demonstrate depletion exacerbates damage facilitating response, leading to severe injury. These results suggest as subpopulation inflammation, beneficial controlling development ischemia promoting recovery from Regulation right time be potential target for treatment brain

Language: Английский

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Depletion of iNOS-positive inflammatory cells decelerates neuronal degeneration and alleviates cerebral ischemic damage by suppressing the inflammatory response

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 181, P. 209 - 220

Published: Feb. 10, 2022

Language: Английский

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The COP9 signalosome reduces neuroinflammation and attenuates ischemic neuronal stress in organotypic brain slice culture model

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(9)

Published: Aug. 19, 2023

The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is a deNEDDylase controlling ubiquitination activity of cullin-RING-E3 ligases (CRLs) and thus the levels key cellular proteins. While CSN its catalytic subunit CSN5 have been extensively studied in cancer, role inflammatory neurological diseases less understood. Following verification that expressed mouse human brain, here we neuroinflammation ischemic neuronal damage employing models relevant brain-resident cell types, an ex vivo organotypic brain slice culture model, CRL NEDDylation state-modifying drugs MLN4924 CSN5i-3, which mimic inhibit, respectively, activity. Untargeted mass spectrometry-based proteomics revealed CSN5i-3 substantially alter microglial proteome, including inflammation-related Applying these mimicking endothelial inflammation as well stress by TNF oxygen-glucose-deprivation/reoxygenation (OGD/RO) treatment, could link CSN5/CSN-mediated cullin deNEDDylation to reduction inflammation, attenuated cerebral improved barrier integrity, protection from stress-induced death. Specifically, reduced phagocytic activity, motility, cytokine expression cells, this was linked inhibition inflammation-induced NF-κB Akt signaling. Inversely, Csn5 knockdown increased Moreover, abrogated TNF-induced signaling microvascular cells (hCMECs) rescued hCMEC monolayers OGD/RO-triggered leakage, while exacerbated permeability. In model ischemia/reperfusion stress, protected death, impaired survival. Neuronal attributable activation cytokines, indicated shape tracking TNF-blocking experiments. Our results indicate protective via types involved disease implicate activity-mimicking deNEDDylating potential therapeutics.

Language: Английский

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Immunomodulation: The next target of mesenchymal stem cell-derived exosomes in the context of ischemic stroke

World Journal of Stem Cells, Journal Year: 2023, Volume and Issue: 15(3), P. 52 - 70

Published: March 22, 2023

Ischemic stroke (IS) is the most prevalent form of brain disease, characterized by high morbidity, disability, and mortality. However, there still a lack ideal prevention treatment measures in clinical practice. Notably, transplantation therapy mesenchymal stem cells (MSCs) has been hot research topic stroke. Nevertheless, are risks associated with this cell therapy, including tumor formation, coagulation dysfunction, vascular occlusion. Also, growing number studies suggest that therapeutic effect after MSCs mainly attributed to MSC-derived exosomes (MSC-Exos). And cell-free mediated appears circumvent many difficulties when compared it may be promising new strategy for treating as replacement therapy. Studies suppressing inflammation via modulation immune response an additional option IS. Intriguingly, MSC-Exos mediates inflammatory following IS modulating central nervous system, peripheral immunomodulatory molecules, thereby promoting neurofunctional recovery Thus, paper reviews role, potential mechanisms, post-IS order identify targets.

Language: Английский

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