Interventional strategies for ischemic stroke based on the modulation of the gut microbiota

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 2, 2023

The microbiota-gut-brain axis connects the brain and gut in a bidirectional manner. organism’s homeostasis is disrupted during an ischemic stroke (IS). Cerebral ischemia affects intestinal flora microbiota metabolites. Microbiome dysbiosis, on other hand, exacerbates severity of IS outcomes by inducing systemic inflammation. Some studies have recently provided novel insights into pathogenesis, efficacy, prognosis, treatment-related adverse events microbiome IS. In this review, we discussed view that clinical value personalized therapeutic regimens for Based recent non-clinical stroke, new strategies might be developed modulating bacterial flora. These include dietary intervention, fecal transplantation, probiotics, antibiotics, traditional Chinese medication, gut-derived stem cell transplantation. Although microbiota-targeted intervention optimistic, some issues need to addressed before translation. deeper understanding potential underlying mechanisms, conducting larger longitudinal cohort host responses with multiple layers data, developing standardized protocols reporting analyses, performing assessment large-scale cohorts. presented certain opportunities challenges considered effective manipulating improve treatment prevention stroke.

Language: Английский

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Untargeted metabonomic analysis of a cerebral stroke model in rats: a study based on UPLC–MS/MS

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Aug. 8, 2023

Introduction Brain tissue damage caused by ischemic stroke can trigger changes in the body’s metabolic response, and understanding response of gut after contribute to research on poststroke brain function recovery. Despite increase international mechanisms availability powerful tools recent years, there is still an urgent need for studies. Metabolomic examination feces from a cerebral ischemia–reperfusion rat model provide new insights into metabolism identify key pathways, which will help reveal diagnostic therapeutic targets as well inspire pathophysiological studies stroke. Methods We randomly divided 16 healthy adult pathogen-free male Sprague–Dawley (SD) rats normal group study group, received middle artery occlusion/reperfusion (MCAO/R). Ultra-performance liquid chromatography–tandem mass spectrometry (UPLCMS/MS) was used determine identities concentrations metabolites across all groups, filtered high-quality data were analyzed differential screening metabolite functional analysis. Results After 1 14 days modeling, compared showed significant neurological deficits ( p < 0.001) significantly increased infarct volume (day 1: 0.001; day 14: = 0.001). Mass spectra identified 1,044 635 positive negative ion modes, respectively, differed between groups. The with levels involved tryptophan 0.036678, 0.05), arachidonic acid 0.15695), cysteine methionine 0.24705), pyrimidine 0.3413), whereas decreased arginine proline 0.15695) starch sucrose 0.52256). Discussion determined that UPLC–MS/MS could be employed untargeted metabolomics research. Moreover, pathways may have been disordered group. Alterations metabolome additional theoretical support elucidating pathogenesis selecting intervention.

Language: Английский

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Research progress and challenges of stem cell therapy for ischemic stroke

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 8, 2024

Ischemic stroke is a significant global cause of death and disability. Currently, treatment options for acute ischemic are limited to intravenous thrombolysis mechanical recanalization. Therefore, novel neuroprotective strategies imperative. Stem cell transplantation possesses the capabilities differentiation, proliferation, neuronal replacement, nerve pathway reconstruction, secretion growth factors, enhancement microenvironment; thus, it potential therapeutic approach stroke. In addition, immunomodulatory function stem cells combined exosomes exhibit favorable protective effect on brain injury neurological dysfunction following Meanwhile, theory microbiota-gut-brain axis provides us with perspective comprehending managing diseases. Lastly, has demonstrated promising outcomes not only in treating but also dealing other disorders, such as tumors. Furthermore, challenges related tissue source, delivery method, immune response, timing still need be addressed optimize treatment.

Language: Английский

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Identification and Validation of Active Ingredient in Cerebrotein Hydrolysate-I Based on Pharmacokinetic and Pharmacodynamic Studies

Drug Metabolism and Disposition, Journal Year: 2023, Volume and Issue: 51(12), P. 1615 - 1627

Published: Sept. 27, 2023

Cerebrotein hydrolysate-1 (CH-1), a mixture of small peptides, polypeptides, and various amino acids derived from porcine brain, has been widely used in the treatment cerebral injury. However, bioactive composition pharmacokinetics CH-1 are still unexplored because their complicated relatively tiny amounts vivo. Herein, NanoLC Orbitrap Fusion Lumos Tribrid Mass Spectrometer was firstly to qualitatively analyze components CH-1. A total 1347 peptides were identified, which 43 characterized by high mass spectrometry (MS) intensity identification accuracy. We then innovatively synthesized four main for activity verification, results suggested that Pep72 (NYEPPTVVPGGDL) had strongest neuroprotective effect on both vivo vitro models. Next, quantitative method established based liquid chromatography tandem (LC-MS/MS) with aid Skyline software its pharmacokinetic studies. The revealed elimination rate low exposure rats. In addition, hCMEC/D3-based model built investigate transport Pep72. found extremely blood-brain barrier permeability not substrate efflux transporters. biotransformation rat fresh plasma tissues investigated explore contradiction between efficacy. 11 metabolites structurally PGGDL EPPTVPGGDL being Notably, metalloproteinase cysteine protease confirmed be enzymes mediating metabolism tissues. SIGNIFICANCE STATEMENT: applied discover CH-1, one peptide have among identified Our study is first time identify verify active ingredient perspective pharmacodynamics, provides systematic technical platforms strategies substance research other protein hydrolysates.

Language: Английский

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Investigation of the effects of Periplaneta americana (L.) extract on ischemic stroke based on combined multi-omics of gut microbiota

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 28, 2024

Ischemic stroke (IS) is a highly lethal type of cardiovascular and cerebrovascular disease. Improving survival rates promoting recovery in patients with IS pose significant challenges, however, recent research has identified the gut–brain axis as therapeutic target. In this study, we evaluated regulatory effect Periplaneta americana (L.) extract (PAS840), which established anti-inflammatory, antioxidant, neuroprotective effects, on gut microbiota using rat model temporary middle cerebral artery occlusion (tMCAO). We protective effects PAS840 brain damage rats through TTC (triphenyltetrazolium chloride), Nissl staining, pathological section analysis. Additionally, investigated impact metabolites 16S rRNA sequencing, untargeted metabolomics contents, transcriptomics analyses tissues to explore its mechanism action. intervention resulted changes microbiota, including an increase abundance probiotic flora, decrease harmful metabolite profiles. It also attenuated damage, decreased platelet activity, inhibited oxidative stress genes related inflammation, improved neurological function rats. These findings suggest that preventive against via by regulating metabolites. Accordingly, candidate drug for further research.

Language: Английский

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