The bidirectional role of the JAK2/STAT3 signaling pathway and related mechanisms in cerebral ischemia-reperfusion injury

Experimental Neurology, Год журнала: 2021, Номер 341, С. 113690 - 113690

Опубликована: Март 31, 2021

Язык: Английский

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Glial Cells as Therapeutic Approaches in Brain Ischemia-Reperfusion Injury

Cells, Год журнала: 2021, Номер 10(7), С. 1639 - 1639

Опубликована: Июнь 30, 2021

Ischemic stroke is the second cause of mortality and first long-term disability constituting a serious socioeconomic burden worldwide. Approved treatments include thrombectomy rtPA intravenous administration, which, despite their efficacy in some cases, are not suitable for great proportion patients. Glial cell-related therapies progressively overcoming inefficient neuron-centered approaches preclinical phase. Exploiting ability microglia to naturally switch between detrimental protective phenotypes represents promising therapeutic treatment, similar way what happens with astrocytes. However, duality present many roles these cells upon ischemia poses notorious difficulty disentangling precise pathways target. Still, promoting M2/A2 microglia/astrocyte inhibiting M1/A1 neurotoxic profiles globally rendering results different vivo models stroke. On other hand, described oligodendrogenesis after brain seems be strictly beneficial, although less studied players paradigm negative effects could oligodendrocytes next years. Here, we review recent advances understanding role mentioned glial cell types main pathological events ischemic stroke, including inflammation, blood barrier integrity, excitotoxicity, reactive oxygen species management, metabolic support, neurogenesis, among others, special attention tested approaches.

Язык: Английский

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Effects of Microglial Activation and Polarization on Brain Injury After Stroke

Frontiers in Neurology, Год журнала: 2021, Номер 12

Опубликована: Июль 1, 2021

Stroke is one of the most common causes death worldwide. The subsequent development neuroinflammation and brain edema dramatically increases risks associated with stroke, leading to a substantial increase in mortality. Although considerable progress has been made improving cerebral perfusion acute phase effective treatment options for subacute chronic phases infarction are limited. Microglia, innate immune cells central nervous system (CNS), can be activated polarized take on different phenotypes response stimulations including pro-inflammatory anti-inflammatory phenotypes, which affect prognosis stroke. Therefore, investigation activation polarizing mechanisms microglia plays critical role treating aim this article was investigate significance microglial phenotype regulation stroke by summarizing activation, mechanisms, general characteristics.

Язык: Английский

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Neuroinflammatory In Vitro Cell Culture Models and the Potential Applications for Neurological Disorders

Frontiers in Pharmacology, Год журнала: 2021, Номер 12

Опубликована: Апрель 23, 2021

Cell cultures are used in pharmaceutical, medical and biological sciences. Due to the ethical cost limitations of

Язык: Английский

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Melatonin and Microglia

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(15), С. 8296 - 8296

Опубликована: Авг. 2, 2021

Melatonin interacts in multiple ways with microglia, both directly and, via routes of crosstalk astrocytes and neurons, indirectly. These effects melatonin are relevance terms antioxidative protection, not only concerning free-radical detoxification, but also prevention processes that cause, promote, or propagate oxidative stress neurodegeneration, such as overexcitation, toxicological insults, viral bacterial infections, sterile inflammation different grades. The immunological interplay the CNS, microglia playing a central role, is high complexity includes signaling toward endothelial cells other leukocytes by cytokines, chemokines, nitric oxide, eikosanoids. interferes these steps. In addition to canonical signal transduction MT1 MT2 receptors, secondary tertiary has be considered, e.g., upregulation sirtuins modulation pro- anti-inflammatory microRNAs. Many details macrophage functionality obviously applicable microglial cells. Of particular interest polarization M2 subtypes instead M1, i.e., favor being at expense proinflammatory activities, which well-documented macrophages applies microglia.

Язык: Английский

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The Role of NLRP3 Inflammasome in Cerebrovascular Diseases Pathology and Possible Therapeutic Targets

ASN NEURO, Год журнала: 2021, Номер 13, С. 175909142110181 - 175909142110181

Опубликована: Янв. 1, 2021

Cerebrovascular diseases are pathological conditions involving impaired blood flow in the brain, primarily including ischaemic stroke, intracranial haemorrhage, and subarachnoid haemorrhage. The nucleotide-binding oligomerisation (NOD) domain-like receptor (NLR) family pyrin domain (PYD)-containing 3 (NLRP3) inflammasome is a protein complex vital component of immune system. Emerging evidence has indicated that NLRP3 plays an important role cerebrovascular diseases. function pathogenesis remains interesting field research. In this review, we first summarised mechanism aggravating atherosclerosis Second, outlined signalling pathways through which participates or mitigating Reactive oxygen species (ROS)/nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB), ROS/thioredoxin-interacting (TXNIP) purinergic receptor-7 (P2X7R) can activate inflammasome; activation aggravate by mediating apoptosis pyroptosis. Autophagy/mitochondrial autophagy, nuclear E2-related factor-2 (Nrf2), interferon (IFN)-β, sirtuin (SIRT), phosphoinositide 3-kinase (PI3K)/protein kinase (AKT) reportedly alleviate inhibiting activation. Finally, explored specific inhibitors based on two-step inflammasome, be developed as new drugs to treat

Язык: Английский

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Cellular and Molecular Targets for Non-Invasive, Non-Pharmacological Therapeutic/Rehabilitative Interventions in Acute Ischemic Stroke

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(2), С. 907 - 907

Опубликована: Янв. 14, 2022

Cerebral circulation delivers the blood flow to brain through a dedicated network of sanguine vessels. A healthy human can regulate cerebral (CBF) according any physiological or pathological challenges. The is protected by its self-regulatory mechanisms, which are dependent on neuronal and support cellular populations, including endothelial ones, as well metabolic, even myogenic factors.Accumulating data suggest that "non-pharmacological" approaches might provide new opportunities for stroke therapy, such electro-/acupuncture, hyperbaric oxygen hypothermia/cooling, photobiomodulation, therapeutic gases, transcranial direct current stimulations, magnetic stimulations. We reviewed recent mechanisms clinical implications these non-pharmaceutical treatments.To present state-of-the-art currently available non-invasive, non-pharmacological-related interventions in acute ischemic stroke, we accomplished this synthetic systematic literature review based Preferred Reporting Items Systematic Principles Reviews Meta-Analyses (PRISMA).The initial number obtained articles was 313. After fulfilling five steps filtering/selection methodology, 54 fully eligible papers were selected review. enhanced our documentation with other bibliographic resources connected subject, identified within non-standardized search, fill knowledge gaps. Fifteen trials also identified.Non-invasive, non-pharmacological therapeutic/rehabilitative mainly holistic therapies. Therefore, most them not yet routinely used practice, despite some possible beneficial effects, have be supplementarily proven more related studies. Moreover, few already completed do final results.This synthesizes findings interventions, described non-invasive non-pharmacological.

Язык: Английский

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Redox Biology of Melatonin: Discriminating Between Circadian and Noncircadian Functions

Antioxidants and Redox Signaling, Год журнала: 2022, Номер 37(10-12), С. 704 - 725

Опубликована: Янв. 12, 2022

Melatonin has not only to be seen as a regulator of circadian clocks. In addition its chronobiotic functions, it displays other actions, especially in cell protection. This includes antioxidant, anti-inflammatory, and mitochondria-protecting effects. Although protection is also modulated by the system, respective actions melatonin can distinguished differ with regard dose requirements therapeutic settings. It aim this article outline these differences terms function, signaling, dosage. Focus been placed on both nexus dissecting properties between noncircadian mechanisms. consider details beyond classic view melatonin's role, such widespread synthesis extrapineal tissues, formation mitochondria, effects mitochondrial permeability transition pore, secondary for example, via upregulation sirtuins regulating noncoding RNAs, microRNAs. The relevance findings, connections functions shed light regulation inflammation, including macrophage/microglia polarization, damage-associated molecular patterns, avoidance cytokine storms, numerous consequences antioxidative protection, that is, aspects high actuality deadly viral bacterial diseases. Antioxid. Redox Signal. 37, 704–725.

Язык: Английский

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Gut microbiota-derived melatonin from Puerariae Lobatae Radix-resistant starch supplementation attenuates ischemic stroke injury via a positive microbial co-occurrence pattern

Pharmacological Research, Год журнала: 2023, Номер 190, С. 106714 - 106714

Опубликована: Фев. 28, 2023

Ischemic stroke is closely associated with gut microbiota dysbiosis and intestinal barrier dysfunction. Prebiotic intervention could modulate the microbiota, thus considered a practical strategy for neurological disorders. Puerariae Lobatae Radix-resistant starch (PLR-RS) potential novel prebiotic; however, its role in ischemic remains unknown. This study aimed to clarify effects underlying mechanisms of PLR-RS stroke. Middle cerebral artery occlusion surgery was performed establish model rats. After gavage 14 days, attenuated stroke-induced brain impairment Moreover, rescued enriched Akkermansia Bifidobacterium. We transplanted fecal from PLR-RS-treated rats into found that colon damage were also ameliorated. Notably, we promoted produce higher level melatonin. Intriguingly, exogenous melatonin injury. In particular, via positive co-occurrence pattern microecology. Specific beneficial bacteria served as leaders or keystone species homeostasis, such Enterobacter, Bacteroidales_S24–7_group, Prevotella_9, Ruminococcaceae Lachnospiraceae. Thus, this new mechanism explain therapeutic efficacy on at least partly attributed microbiota-derived summary, improving microecology by prebiotic supplementation be effective therapies

Язык: Английский

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The Relationship of Astrocytes and Microglia with Different Stages of Ischemic Stroke

Current Neuropharmacology, Год журнала: 2023, Номер 21(12), С. 2465 - 2480

Опубликована: Июль 19, 2023

Abstract: Ischemic stroke is the predominant cause of severe morbidity and mortality worldwide. Post-stroke neuroinflammation has recently received increasing attention with aim providing a new effective treatment strategy for ischemic stroke. Microglia astrocytes are major components innate immune system central nervous system. They can be involved in all phases stroke, from early stage, contributing to first wave neuronal cell death, late stage involving phagocytosis repair. In vicious cycle exists between activation microglia (through astrocytic connexin 43 hemichannels), aggravating neuroinflammatory injury post-stroke. However, repeatedly activated induce formation glial scars by triggering reactive astrogliosis peri-infarct regions, which may limit movement reverse restrict diffusion inflammation healthy brain tissues, alleviating poststroke. this review, we elucidated various roles summarized their relationship neuroinflammation. We also examined how influence each other at different stages Several potential therapeutic approaches targeting have been reviewed. Understanding details astrocytemicroglia interaction processes will contribute better understanding mechanisms underlying identification interventions.

Язык: Английский

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