Stem Cell Reviews and Reports, Journal Year: 2023, Volume and Issue: 19(6), P. 1907 - 1921
Published: April 26, 2023
Language: Английский
Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(12), P. 737 - 753
Published: Nov. 13, 2023
Language: Английский
Citations
68
Advanced Science, Journal Year: 2024, Volume and Issue: 11(19)
Published: March 14, 2024
Abstract Mitochondrial dysfunction contributes to the development of secondary brain injury (SBI) following intracerebral hemorrhage (ICH) and represents a promising therapeutic target. Celastrol, primary active component Tripterygium wilfordii , is natural product that exhibits mitochondrial neuronal protection in various cell types. This study aims investigate neuroprotective effects celastrol against ICH‐induced SBI explore its underlying mechanisms. Celastrol improves neurobehavioral cognitive abilities mice with autologous blood‐induced ICH, reduces death vivo vitro, promotes function recovery neurons. Single‐cell nuclear sequencing reveals cyclic adenosine monophosphate (cAMP)/cAMP‐activated exchange protein‐1 (EPAC‐1) signaling pathways are impacted by celastrol. binds cNMP (a domain EPAC‐1) inhibit interaction voltage‐dependent anion‐selective channel protein 1 (VDAC1) blocks opening permeability transition pores. After neuron‐specific knockout EPAC1, diminished. In summary, this demonstrates celastrol, through EPAC‐1, ameliorates neurons, thus potentially improving induced ICH. These findings suggest targeting EPAC‐1 can be approach for treating SBI.
Language: Английский
Citations
22
EBioMedicine, Journal Year: 2024, Volume and Issue: 101, P. 104993 - 104993
Published: Feb. 6, 2024
BackgroundMacrophages are innate immune cells whose phagocytosis function is critical to the prognosis of stroke and peritonitis. cis-aconitic decarboxylase immune-responsive gene 1 (Irg1) its metabolic product itaconate inhibit bacterial infection, intracellular viral replication, inflammation in macrophages. Here we explore whether regulates phagocytosis.MethodsPhagocytosis macrophages was investigated by time-lapse video recording, flow cytometry, immunofluorescence staining macrophage/microglia cultures isolated from mouse tissue. Unbiased RNA-sequencing ChIP-sequencing assays were used underlying mechanisms. The effects Irg1/itaconate axis on intracerebral hemorrhagic (ICH) peritonitis observed transgenic (Irg1flox/flox; Cx3cr1creERT/+, cKO) mice or control vivo.FindingsIn a model ICH, depletion Irg1 decreased erythrocytes, thereby exacerbating outcomes (n = 10 animals/group, p < 0.05). Administration sodium itaconate/4-octyl (4-OI) promoted macrophage 7 In addition, peritonitis, deficiency also inhibited Staphylococcus aureus 5 0.05) aggravated 9 Mechanistically, 4-OI alkylated cysteine 155 Kelch-like ECH-associated protein (Keap1), consequent nuclear translocation factor erythroid 2-related 2 (Nrf2) transcriptional activation Cd36 gene. Blocking CD36 completely abolished phagocytosis-promoting vitro vivo.InterpretationOur findings provide potential therapeutic target for phagocytosis-deficiency disorders, supporting further development towards clinical application benefit patients.FundingThe National Natural Science Foundation China (32070735, 82371321 Q. Li, 82271240 F. Yang) Beijing Program Scientific Research Key Municipal Commission Education (KZ202010025033 Li).
Language: Английский
Citations
18
Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(4), P. 1155 - 1155
Published: Feb. 11, 2025
Background: Spontaneous intracerebral hemorrhage (ICH) accounts for approximately 20% of all strokes and is associated with high mortality disability rates. Despite numerous trials, conventional surgical approaches have not demonstrated consistent improvements in functional outcomes. Minimally invasive surgery (MIS) ICH evacuation has emerged as a promising alternative, the potential to improve outcomes reduce mortality. Objectives: This narrative review aims provide comprehensive overview various MIS techniques their reported impact on patients spontaneous while discussing key limitations existing literature. Methods: We systematically searched PubMed identify studies published from 1 January 2010 22 March 2024. The search strategy included following terms: ("minimally*"[All Fields] AND "invasive*"[All "surgery*"[All "intracerebral*"[All "hemorrhage*"[All Fields]) (2010:2024[pdat]). focuses randomized controlled trials (RCTs) that evaluate clinical Results: Our identified six RCTs conducted between 2024, encompassing 2180 mean age 58.03 ± 4.5 years. Four significantly improved recovery (mRs ≤ 3), reduced mortality, fewer adverse events compared standard medical management or craniotomy. All rely stereotactic planning use tools such exoscopes, endoscopes, craniopuncture, thrombolytic irrigation precise hematoma evacuation. These brain tissue disruption precision. However, variability techniques, costs, lack an external validation limit generalizability these findings. Conclusions: shows alternative strategies ICH, offering encouraging evidence selected studies. findings remain limited by gaps literature, including need validation, significant methodological heterogeneity, economic challenges. Further rigorous are essential confirm long-term approaches.
Language: Английский
Citations
3
Biomaterials, Journal Year: 2025, Volume and Issue: 319, P. 123212 - 123212
Published: Feb. 24, 2025
Language: Английский
Citations
3
Cells, Journal Year: 2022, Volume and Issue: 11(14), P. 2152 - 2152
Published: July 8, 2022
Iron is responsible for the regulation of several cell functions. However, iron ions are catalytic and dangerous cells, so cells sequester such redox-active irons in transport storage proteins. In systemic overload local pathological conditions, increases human body induces oxidative stress through formation reactive oxygen species. Non-transferrin bound a candidate extracellular space. Cells take by uptake machinery as transferrin receptor divalent metal transporter 1. These delivered to places where they needed poly(rC)-binding proteins 1/2 excess stored ferritin or released out ferroportin We can imagine transit pool from import export. Since another iron, size may be kept minimally. When large amount enters overflows capacity binding proteins, behaves cell. This review focuses on intracellular spaces biophysical chemical point view.
Language: Английский
Citations
45
Molecules, Journal Year: 2022, Volume and Issue: 27(20), P. 7080 - 7080
Published: Oct. 20, 2022
Intracerebral hemorrhage (ICH) is the most lethal subtype of stroke, but effective treatments are lacking, and neuroinflammation plays a key role in pathogenesis. In innate immune response to cerebral hemorrhage, microglia first appear around injured tissue involved inflammatory cascade response. Microglia respond acute brain injury by being activated polarized either typical M1-like (pro-inflammatory) or an alternative M2-like (anti-inflammatory) phenotype. These two polarization states produce pro-inflammatory anti-inflammatory. With discovery molecular mechanisms signaling molecules related brain, some targets that regulate reduce considered treatment for secondary after ICH damage strategies. Therefore, how promote M2 phenotype has become focus attention recent years. This article reviews mechanism action microglia’s M1 phenotypes ICH. Moreover, it discusses compounds natural pharmaceutical ingredients can polarize
Language: Английский
Citations
40
Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 179, P. 106044 - 106044
Published: Feb. 17, 2023
Stroke is the second leading cause of death worldwide; however, treatment choices available to neurologists are limited in clinical practice. Lipocalin 2 (LCN2) a secreted protein, belonging lipocalin superfamily, with multiple biological functions mediating innate immune response, inflammatory iron-homeostasis, cell migration and differentiation, energy metabolism, other processes body. LCN2 expressed at low levels brain under normal physiological conditions, but its expression significantly up-regulated acute stimulations chronic pathologies. An up-regulation has been found blood/cerebrospinal fluid patients ischemic/hemorrhagic stroke, could serve as potential biomarker for prediction severity stroke. activates reactive astrocytes microglia, promotes neutrophil infiltration, amplifies post-stroke inflammation, blood-brain barrier disruption, white matter injury, neuronal death. Moreover, involved injury induced by thrombin erythrocyte lysates, well microvascular thrombosis after hemorrhage. In this paper, we review role pathological ischemic stroke; intracerebral hemorrhage; subarachnoid stroke-related diseases, such vascular dementia depression, their underlying mechanisms. We hope that will help elucidate value therapeutic target
Language: Английский
Citations
37
Small, Journal Year: 2023, Volume and Issue: 19(23)
Published: March 12, 2023
Abstract Neurological diseases are the foremost cause of disability and second leading death worldwide. Owing to special microenvironment neural tissues biological characteristics cells, a considerable number neurological disorders currently incurable. In past few years, development nanoplatforms based on metal–organic frameworks (MOFs) has broadened opportunities for offering sensitive diagnosis/monitoring effective therapy neurology‐related diseases. this article, obstacles neurotherapeutics, including delayed diagnosis misdiagnosis, existence blood brain barrier (BBB), off‐target treatment, irrepressible inflammatory storm/oxidative stress, irreversible nerve cell summarized. Correspondingly, MOFs‐based diagnostic/monitoring strategies such as neuroimaging biosensors (electrochemistry, fluorometry, colorimetry, electrochemiluminescence, etc.) therapeutic higher BBB permeability, targeting specific lesion sites, attenuation neuroinflammation/oxidative stress well regeneration extensively highlighted management Finally, challenges present research from perspective clinical translation discussed, hoping facilitate interdisciplinary studies at intersections between neurotheranostics.
Language: Английский
Citations
37
Stroke, Journal Year: 2023, Volume and Issue: 54(6), P. 1548 - 1557
Published: May 22, 2023
Major intracerebral hemorrhage (ICH) trials have largely been unable to demonstrate therapeutic benefit in improving functional outcomes. This may be partly due the heterogeneity of ICH outcomes based on their location, where a small strategic could debilitating, thus confounding effects. We aimed determine ideal hematoma volume cutoff for different locations predicting retrospectively analyzed consecutive patients enrolled University Hong Kong prospective stroke registry from January 2011 December 2018. Patients with premorbid modified Rankin Scale score >2 or who underwent neurosurgical intervention were excluded. cutoff, sensitivity, and specificity respective 6-month neurological (good [modified 0-2], poor 4-6], mortality) specific determined using receiver operating characteristic curves. Separate multivariate logistic regression models also conducted each location-specific whether these cutoffs independently associated Among 533 ICHs, good outcome according location was 40.5 mL lobar, 32.5 putamen/external capsule, 5.5 internal capsule/globus pallidus, 6.5 thalamus, 17 cerebellum, 3 brainstem. smaller than all supratentorial sites had higher odds (all P<0.05). Volumes exceeding 48 41 6 9.5 22 7.5 brainstem at greater risk Mortality risks significantly volumes that exceeded 89.5 42 21 pallidus P<0.001). All discriminant values (area under curve >0.8), except cerebellum. differed size. Location-specific should considered patient selection trials.
Language: Английский
Citations
34