Scientific Reports, Год журнала: 2025, Номер 15(1)
Опубликована: Май 23, 2025
Язык: Английский
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(4), С. 2372 - 2372
Опубликована: Фев. 17, 2024
A traumatic brain injury (TBI) is a major health issue affecting many people across the world, causing significant morbidity and mortality. TBIs often have long-lasting effects, disrupting daily life functionality. They cause two types of damage to brain: primary secondary. Secondary particularly critical as it involves complex processes unfolding after initial injury. These can lead cell death in brain. Understanding how these crucial for finding new treatments. This review examines wide range literature from 2021 2023, focusing on biomarkers molecular mechanisms pinpoint therapeutic advancements. Baseline levels biomarkers, including neurofilament light chain (NF-L), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), Tau, glial fibrillary acidic protein (GFAP) TBI, demonstrated prognostic value cognitive outcomes, laying groundwork personalized treatment strategies. In terms pharmacological progress, most promising approaches currently target neuroinflammation, oxidative stress, apoptotic mechanisms. Agents that modulate pathways offer potential reduce TBI's impact aid neurological rehabilitation. Future research poised refine approaches, potentially revolutionizing TBI treatment.
Язык: Английский
Процитировано
22
CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 29(8), С. 2236 - 2258
Опубликована: Март 8, 2023
Abstract Aims Recently, human umbilical cord mesenchymal stem cell (HucMSC)‐derived exosome is a new focus of research in neurological diseases. The present study was aimed to investigate the protective effects HucMSC‐derived both vivo and vitro TBI models. Methods We established mouse neuron models our study. After treatment with exosome, neuroprotection investigated by neurologic severity score (NSS), grip test score, brain water content, cortical lesion volume. Moreover, we determined biochemical morphological changes associated apoptosis, pyroptosis, ferroptosis after TBI. Results revealed that could improve function, decrease cerebral edema, attenuate Furthermore, administration suppressed TBI‐induced death, ferroptosis. In addition, exosome‐activated phosphatase tensin homolog‐induced putative kinase protein 1/Parkinson 2 E3 ubiquitin–protein ligase (PINK1/Parkin) pathway‐mediated mitophagy However, attenuated when inhibited, PINK1 knockdown. Importantly, also decreased activated PINK1/Parkin vitro. Conclusion Our results provided first evidence played key role through mitophagy.
Язык: Английский
Процитировано
39
Cell Death and Disease, Год журнала: 2024, Номер 15(7)
Опубликована: Июль 16, 2024
Abstract During oxidative phosphorylation, mitochondria continuously produce reactive oxygen species (ROS), and untimely ROS clearance can subject to stress, ultimately resulting in mitochondrial damage. Mitophagy is essential for maintaining cellular quality control homeostasis, with activation involving both ubiquitin-dependent ubiquitin-independent pathways. Over the past decade, numerous studies have indicated that different forms of regulated cell death (RCD) are connected mitophagy. These diverse RCD been shown be by mitophagy implicated pathogenesis a variety diseases, such as tumors, degenerative ischemia‒reperfusion injury (IRI). Importantly, targeting regulate has excellent therapeutic potential preclinical trials, expected an effective strategy treatment related diseases. Here, we present summary role RCD, focus on molecular mechanisms which regulates RCD. We also discuss implications mitophagy-related context various
Язык: Английский
Процитировано
16
Nano Today, Год журнала: 2024, Номер 58, С. 102438 - 102438
Опубликована: Авг. 13, 2024
Язык: Английский
Процитировано
15
Acta Pharmacologica Sinica, Год журнала: 2024, Номер unknown
Опубликована: Авг. 23, 2024
Язык: Английский
Процитировано
10
ACS Chemical Neuroscience, Год журнала: 2025, Номер unknown
Опубликована: Фев. 4, 2025
This study investigated the therapeutic potential of exosomes from human umbilical cord mesenchymal stem cells (huMSCs), focusing on PTEN-induced kinase 1 (PINK1) and its impact exosome efficacy. Postmodification, were administered to a murine model intracranial hemorrhage (ICH). Assessments included brain edema, neurological function, anxiety-like behaviors, inflammatory responses, microglial polarization. We observed that administration control huMSCs significantly reduced water content, indicating reduction in as quantitatively assessed through content analysis. Neurological evaluated using standard scoring system, showed marked improvement animals treated with compared those receiving PINK1-deficient exosomes, highlighting importance PINK1 mediating recovery. Additionally, substantially decreased behaviors Open Field Test, demonstrated by immobility times increased exploratory behavior. Inflammatory response assessments favorable shift levels pro-inflammatory cytokines (MCP-1, IL-1β, TNF-α) anti-inflammatory cytokine IL-10 exosome-treated groups. Furthermore, analysis polarization revealed toward M2 phenotype, evidenced M1 markers (Cd86, Iba1) (Arg1, Cd206) group. Taken together, we found efficacy ICH treatment normal expression. Our findings underscore critical role enhancing huMSC-derived treatment.
Язык: Английский
Процитировано
1
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2491 - 2491
Опубликована: Март 11, 2025
Exosomes, which are nano-sized natural vesicles secreted by cells, crucial for intercellular communication and interactions, playing a significant role in various physiological pathological processes. Their characteristics, such as low toxicity immunogenicity, high biocompatibility, remarkable drug delivery capabilities—particularly their capacity to traverse the blood–brain barrier—make exosomes highly promising vehicles administration treatment of brain disorders. This review provides comprehensive overview exosome biogenesis isolation techniques, strategies loading functionalization exosomes, exosome-mediated barrier penetration mechanisms, with particular emphasis on recent advances exosome-based Finally, we address opportunities challenges associated utilizing system brain, summarizing barriers clinical translation proposing future research directions.
Язык: Английский
Процитировано
1
Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)
Опубликована: Апрель 5, 2025
Mitochondria play a critical role in oxidative stress (OS)-induced neuronal injury during ischemic stroke (IS), making them promising therapeutic targets. Mounting evidence underscores the extraordinary promise of exosomes derived from human neural stem cells (hNSCs) management central nervous system (CNS) diseases. Nonetheless, precise mechanisms by which these target mitochondria to ameliorate effects IS remain only partially elucidated. This study investigates protective hNSC (hNSC-Exos) on damage. Using rat model middle cerebral artery occlusion (MCAO) vivo and OS-induced HT22 vitro. Firstly, our research group independently isolated subsequently prepared hNSC-Exos. In vivo, MCAO rats were restored blood flow perfusion simulate ischemia-reperfusion injury, hNSC-Exos injected through stereotaxic injection into brain. Subsequently, evaluated, including histological studies, behavioral assessments. H2O2 was used OS environment MCAO, then its evaluated co-culturing with hNSC-Exos, immunofluorescence staining, western blotting (WB), quantitative real time PCR (qRT-PCR). process exploring specific mechanisms, we utilized RNA sequencing (RNA-seq) detect potential induction mitophagy cells. Afterwards, employed series mitochondrial function assessments autophagy related detection techniques, measuring membrane potential, reactive oxygen species (ROS) levels, transmission electron microscopy (TEM) imaging, monodansylcadaverine (MDC) mCherry-GFP-LC3B staining. addition, further investigated regulatory pathway using inhibitor mdivi-1 knocking out PTEN induced kinase 1 (PINK1) Administration significantly ameliorated brain tissue damage enhanced outcomes rats. treatment led reduction apoptosis facilitated normalization impaired neurogenesis neuroplasticity. Notably, application vitro resulted an upregulation cells, thereby remedying dysfunction. We demonstrate that activate via PINK1/Parkin pathway, improving reducing apoptosis. These findings suggest alleviate regulating pathway. reveals novel cell-derived therapy promoting neuroprotection their as approach for OS-associated CNS diseases, IS.
Язык: Английский
Процитировано
1
Free Radical Biology and Medicine, Год журнала: 2023, Номер 208, С. 319 - 333
Опубликована: Авг. 26, 2023
Язык: Английский
Процитировано
17
Life, Год журнала: 2023, Номер 13(9), С. 1924 - 1924
Опубликована: Сен. 16, 2023
(1) Background: In this study, we aimed to explore the regulatory mechanism of miR-124-3p microglial exosomes, as they were previously reported modulate neuroinflammation and promote neuronal repair following traumatic brain injury (TBI). (2) Methods: Studies investigating impact exosomal miRNAs, specifically miR-124-3p, on injured neurons microvascular endothelial cells (BMVECs) in context TBI reviewed. (3) Results: Animal models TBI, vitro cell culture experiments, RNA sequencing analysis, functional assays employed elucidate mechanisms underlying effects miR-124-3p-loaded exosomes repair. Anti-inflammatory M2 polarization microglia, mTOR signaling suppression, BMVECs-mediated autophagy main processes contributing neuroprotection, reduced blood-brain barrier leakage, improved neurologic outcomes animal TBI. (4) Conclusions: Microglial particularly those carrying have emerged promising candidates for therapeutic interventions These exhibit neuroprotective effects, attenuate neuroinflammation, plasticity. However, further research is required fully optimize their delivery strategies effective treatment human cases.
Язык: Английский
Процитировано
17