Colloids and Surfaces B Biointerfaces, Journal Year: 2024, Volume and Issue: 239, P. 113938 - 113938
Published: May 3, 2024
Language: Английский
Molecular Therapy, Journal Year: 2022, Volume and Issue: 31(5), P. 1207 - 1224
Published: Oct. 17, 2022
Developing strategies toward safe and effective drug delivery into the central nervous system (CNS) with improved targeting abilities reduced off-target effects is crucial. CNS-targeted carriers made of synthetic molecules raise concerns about their biodegradation, clearance, immune responses, neurotoxicity. Cell-derived nanovesicles (CDNs) have recently been applied in delivery, because intrinsic stability, biocompatibility, inherent homing capability, ability to penetrate through biological barriers, including blood-brain barrier. Among these CDNs, extracellular vesicles exosomes are most studied surface can be engineered modified cater brain targeting. In this review, we focus on application CDNs brain-targeted treat neurological diseases. We cover developed methods exosome derivation engineering, exosome-like particles, hybrid exosomes, exosome-associated adeno-associated viruses, envelope protein nanocages. Finally, discuss limitations project future development CDN-based systems, conclude that hold great potential treatment
Language: Английский
Citations
87
Theranostics, Journal Year: 2022, Volume and Issue: 12(7), P. 3553 - 3573
Published: Jan. 1, 2022
Rationale: White matter repair is critical for the cognitive and neurological functional recovery after ischemic stroke.M2 microglia are well-documented to enhance remyelination their extracellular vesicles (EVs) mediate cellular function brain injury.However, whether M2 microglia-derived EVs could promote white cerebral ischemia its underlying mechanism largely unknown.Methods: were isolated from IL-4 treated (M2-EVs) untreated (M0-EVs).Adult ICR mice subjected 90-minute transient middle artery occlusion received intravenous treatment seven consecutive days.Brain atrophy volume, neurobehavioral tests examined within 28 days following ischemia.Immunohistochemistry, myelin transmission electron microscope compound action potential measurement performed assess structural remodeling, oligodendrogenesis.The effects of M2-EVs on oligodendrocyte precursor cells (OPCs) also in vitro.EVs' miRNA sequencing, specific miR-23a-5p knockdown luciferase reporter assay used explore mechanism.Results: reduced promoted recovery, oligodendrogenesis vivo, increased OPC proliferation, survival differentiation vitro.miR-23a-5p was enriched maturation, while knocking down reversed beneficial both vitro vivo.Luciferase showed that directly targeted Olig3.Conclusion: Our results demonstrated communicate OPCs through via possibly by targeting Olig3 stroke, suggesting a novel promising therapeutic strategy stroke demyelinating disease.
Language: Английский
Citations
85
Glia, Journal Year: 2024, Volume and Issue: 72(6), P. 1016 - 1053
Published: Jan. 4, 2024
Abstract Microglia play key roles in the post‐ischemic inflammatory response and damaged tissue removal reacting rapidly to disturbances caused by ischemia working restore lost homeostasis. However, modified environment, encompassing ionic imbalances, disruption of crucial neuron–microglia interactions, spreading depolarization, generation danger signals from necrotic neurons, induce morphological phenotypic shifts microglia. This leads them adopt a proinflammatory profile heighten their phagocytic activity. From day three post‐ischemia, macrophages infiltrate core while microglia amass at periphery. Further, inflammation prompts metabolic shift favoring glycolysis, pentose‐phosphate shunt, lipid synthesis. These shifts, combined with intake, drive droplet biogenesis, fuel anabolism, enable proliferation. Proliferating release trophic factors contributing protection repair. some accumulate lipids persistently transform into dysfunctional potentially harmful foam cells. Studies also showed that either display impaired apoptotic cell clearance, or eliminate synapses, viable endothelial Yet, it will be essential elucidate viability engulfed cells, features local extent damage, temporal sequence. Ischemia provides rich variety region‐ injury‐dependent stimuli for microglia, evolving time generating distinct phenotypes including those exhibiting traits others showing pro‐repair features. Accurate profiling phenotypes, alongside more precise understanding associated conditions, is necessary step serve as potential foundation focused interventions human stroke.
Language: Английский
Citations
30
Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16
Published: Aug. 16, 2022
Stroke remains a major cause of long-term disability and mortality worldwide. The immune system plays an important role in determining the condition brain following stroke. As resident innate cells central nervous system, microglia are primary responders defense network covering entire parenchyma, exert various functions depending on dynamic communications with neurons, astrocytes, other neighboring under both physiological or pathological conditions. Microglia activation polarization is crucial for damage repair ischemic stroke, considered double-edged sword neurological recovery. can exist pro-inflammatory states promote secondary damage, but they also secrete anti-inflammatory cytokines neurotrophic factors facilitate recovery In this review, we focus mechanisms microglia-mediated neuroinflammation neuroplasticity after ischemia relevant potential microglia-based interventions stroke therapy.
Language: Английский
Citations
69
Cells, Journal Year: 2021, Volume and Issue: 10(3), P. 565 - 565
Published: March 5, 2021
Myelin is the lipid-rich structure formed by oligodendrocytes (OLs) that wraps axons in multilayered sheaths, assuring protection, efficient saltatory signal conduction and metabolic support to neurons. In last few years, impact of OL dysfunction myelin damage has progressively received more attention now considered be a major contributing factor neurodegeneration several neurological diseases, including amyotrophic lateral sclerosis (ALS). Upon injury, oligodendrocyte precursor cells (OPCs) adult nervous tissue sustain generation new OLs for reconstitution, but this spontaneous regeneration process fails successfully counteract damage. Of note, functions OPCs exceed formation repair myelin, also involve trophic capability exert an immunomodulatory role, which are particularly relevant context neurodegeneration. review, we deeply analyze dysfunctional ALS pathogenesis. The possible mechanisms underlying degeneration, defective OPC maturation, impairment energy supply motor neurons (MNs) have been examined provide insights on future therapeutic interventions. On basis, discuss potential utility molecules, based their remyelinating or enhance metabolism.
Language: Английский
Citations
61
Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13
Published: June 20, 2022
The immune response to ischemic stroke is an area of study that at the forefront research and presents promising new avenues for treatment development. Upon cerebral vessel occlusion, innate system activated by danger-associated molecular signals from stressed dying neurons. Microglia, cell population within central nervous which phagocytose debris modulate via cytokine signaling, are first become activated. Soon after, monocytes arrive peripheral system, differentiate into macrophages, further aid in response. activation, both microglia monocyte-derived macrophages capable polarizing phenotypes can either promote or attenuate inflammatory Phenotypes hypothesized increase neuronal damage impair recovery function during later phases stroke. Therefore, modulating neuroimmune cells adopt anti-inflammatory post current interest potential In this review, we outline biology explain their roles acute, subacute, chronic stages stroke, highlight development efforts target these context
Language: Английский
Citations
59
Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13
Published: Nov. 16, 2022
Ischemic stroke (IS) is one of the major types cerebrovascular diseases causing neurological morbidity and mortality worldwide. In pathophysiological process IS, microglia play a beneficial role in tissue repair. However, it could also cause cellular damage, consequently leading to cell death. Inflammation characterized by activation microglia, increasing evidence showed that autophagy interacts with inflammation through regulating correlative mediators signaling pathways. this paper, we summarized harmful effects IS. addition, discussed interplay between ischemic inflammation, as along its application treatment We believe help provide theoretical references for further study into IS treatments future.
Language: Английский
Citations
57
Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)
Published: Feb. 29, 2024
Abstract Type-2 diabetes (T2D) worsens stroke recovery, amplifying post-stroke disabilities. Currently, there are no therapies targeting this important clinical problem. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) potent anti-diabetic drugs that also efficiently reduce cardiovascular death and heart failure. In addition, SGLT2i facilitate several processes implicated in recovery. However, the potential efficacy of to improve recovery T2D has not been investigated. Therefore, we determined whether a intervention with Empagliflozin could mice. was induced C57BL6J mice by 8 months high-fat diet feeding. Hereafter, animals were subjected transient middle cerebral artery occlusion treated vehicle or SGLTi (10 mg/kg/day) starting from 3 days after stroke. A similar study non diabetic conducted. Stroke assessed using forepaw grip strength test. To identify mechanisms involved Empagliflozin-mediated effects, metabolic parameters assessed. Additionally, neuronal survival, neuroinflammation, neurogenesis vascularization analyzed immunohistochemistry/quantitative microscopy. significantly improved but non-diabetic Improvement functional associated lowered glycemia, increased serum levels fibroblast growth factor-21 (FGF-21), normalization T2D-induced aberration parenchymal pericyte density. The global T2D-epidemic fact is major risk factor for drastically increasing number people need efficacious Our data provide strong incentive use treatment sequelae T2D.
Language: Английский
Citations
12
Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15
Published: Aug. 5, 2021
Stroke remains the leading cause of long-term disability worldwide with significant sequelae. However, there is no highly effective treatment to enhance post-stroke recovery despite extensive efforts in exploring rehabilitative therapies. Neurorehabilitation recognized as cornerstone functional restoration therapy stroke, where treatments are focused on neuroplastic regulation reverse neural structural disruption and improve neurofunctional networks. Post-stroke neuroplasticity changes begin within hours symptom onset reaches a plateau by 3 4 weeks global brain animal studies. It plays determining role spontaneous stroke recovery. Microglia immediately activated following cerebral ischemia, which has been found both proximal primary ischemic injury at remote regions have connections area. exhibit different activation profiles based microenvironment adaptively switch their phenotypes spatiotemporal manner response injuries. Microglial coincides after provides fundamental base for microglia-mediated inflammatory responses involved entire network rewiring repair. exerts important effects including reestablishment neurovascular networks, neurogenesis, axonal remodeling, blood vessel regeneration. In this review, we focus crosstalk between microglial endogenous neuroplasticity, special plastic alterations whole implications stroke. We then summarize recent advances impacts phenotype polarization plasticity, trying discuss potential efficacy microglia-based extrinsic restorative interventions promoting
Language: Английский
Citations
43
Cellular and Molecular Neurobiology, Journal Year: 2021, Volume and Issue: 42(8), P. 2505 - 2525
Published: Aug. 30, 2021
Language: Английский
Citations
42