Circadian Mechanisms in Cardiovascular and Cerebrovascular Disease

Circulation Research, Год журнала: 2024, Номер 134(6), С. 615 - 617

Опубликована: Март 14, 2024

Язык: Английский

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Mechanism of P-Hydroxy Benzyl Alcohol Against Cerebral Ischemia Based on Metabonomics Analysis

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(1), С. 317 - 317

Опубликована: Янв. 1, 2025

Stroke is the leading cause of death and disability worldwide, with ischemic stroke accounting for majority these. HBA active ingredient in Gastrodia elata has potential therapeutic effects on central nervous system diseases. In this study, cell model cerebral ischemia was replicated by culture method oxygen-glucose deprivation/reoxygenation, rat vascular dementia established two-vessel occlusion method. Metabolomics technology employed to analyze metabolic changes neurons induced HBA, targets were verified. The protective their mitochondria examined through multiple indicators, related mechanisms can improve post-ischemic cognitive impairment rats, its mechanism regulation choline-activated phospholipase D2/Sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α pathway mitochondrial function reduce autophagic activity maintain homeostasis. It concluded that a effect neuronal damage caused regulating key metabolites signaling pathways, it provides new molecular target treatment ischemia.

Язык: Английский

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Isoform-selective and non-selective rho-kinase inhibitors do not affect collagenase-induced intracerebral hemorrhage outcomes in mice: Influence of sex and circadian cycle

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Rho-associated protein kinase (ROCK) inhibitors are therapeutic candidates in ischemic stroke and subarachnoid hemorrhage. However, their efficacy intracerebral hemorrhage (ICH) is unknown. Here, we tested the of fasudil (10 mg/kg), an isoform-nonselective ROCK inhibitor, NRL-1049 a novel inhibitor with 43-fold higher selectivity for ROCK2 isoform compared ROCK1, collagenase-induced ICH model mice. Both short (1–3 days) prolonged (14 paradigms were using robust sample sizes both males females active inactive circadian stages. Outcome readouts included weight loss, mortality, hematoma volume, hemispheric swelling, brain water content, BBB permeability to large molecules, sensorimotor cognitive function. We found treatments safe but not efficacious improving disruption, or neurological deficits this model. Intriguingly, however, induction during stage was associated worse tissue behavioral outcomes stage.

Язык: Английский

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2-Deoxy-D-glucose chemical exchange-sensitive spin-lock MRI of cerebral glucose metabolism after stroke in the rat

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

Abstract Rapid breakdown of cerebral glucose metabolism is a hallmark in stroke pathology. Metabolic activity delineates the penumbra from infarct core, representing tissue that potentially salvageable by therapeutic interventions. Tools to image dynamics and its spatial distribution could provide biomarkers disease severity success Here, we developed new protocol measure rat model using chemical exchange-sensitive spin-lock (CESL) MRI analog 2-deoxy-D-glucose (2DG). We further implemented combines 2DG-CESL-MRI with perfusion diffusion relate this signal established definitions hypoperfused tissue, cytotoxic edema penumbra. found provides biomarker disturbed after high effect size. This first study investigate CESL 2DG context imaging rodent stroke.

Язык: Английский

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Melatonin Regulates Glymphatic Function to Affect Cognitive Deficits, Behavioral Issues, and Blood–Brain Barrier Damage in Mice After Intracerebral Hemorrhage: Potential Links to Circadian Rhythms

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(2)

Опубликована: Фев. 1, 2025

ABSTRACT Background Intracerebral hemorrhage (ICH) is a life‐threatening cerebrovascular disorder with no specific pharmacological treatment. ICH causes significant behavioral deficits and cognitive impairments. Recent research suggests that circadian rhythm regulation could be promising therapeutic strategy for ICH. Melatonin has been shown to alleviate glymphatic system (GS) dysfunction by regulating rhythms, thereby improving depressive‐like behaviors postoperative sleep disorders in mice. However, its application treatment mechanisms are not well understood. Methods models were created 8‐to‐10‐week‐old mice using collagenase injection. Circadian modulation was tested melatonin luzindole. Behavioral impairments assessed the modified neurological severity score, corner test, novel object recognition test. Brain water content measured dry/wet weight method, cerebral perfusion blood flow measurements. GS function evaluated RITC‐dextran Evans blue assays. Immunofluorescence western blotting used analyze BBB permeability. Results restored transport after ICH, promoting hematoma edema absorption, reducing damage, outcomes. luzindole partially blocked these benefits reversed neuroprotective effects. Conclusion affect function, permeability, cognitive‐behavioral outcomes The underlying mechanism may involve of rhythms.

Язык: Английский

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LIF and sLIFr alterations during reconvalescence (novel coronavirus infection, influenza) in patients with essential hypertension

Bulletin of Russian State Medical University, Год журнала: 2025, Номер 2025(1)

Опубликована: Фев. 1, 2025

Today, the analysis of risk developing cardiovascular complications in patients with essential hypertension (EH) following recovery from novel coronavirus infection (COVID-19) is relevant. The value leukemia inhibitory factor (LIF) and its soluble receptor (sLIFr) EH progression has been shown, along relevance circadian approaches to assessment contribution pro-inflammatory cytokines pathogenesis acute cerebrovascular accidents (CVA). study aimed compare alterations LIF sLIFr levels during reconvalescence after COVID-19 influenza stage II EH, determine features that are important for development CVA, analyze associations rhythms. was conducted four phases (n = 180; age 55–60 years): (1) 6–8 months before COVID-19; (2–3) on day 10–14 primary or recurrent (4) influenza. In each phase blood were determined by enzyme immunoassay at 7.00–8.00 h 19.00–20.00 h, 12 — 12.00–13.00 23.00–1.00 throughout three days. It demonstrated show elevated relative healthy individuals all time points (р ˂ 0.001) significantly 0.001). relationship between rhythms LIF, post revealed similar changes form larger increase (the ROC data shown predictive CVA within a year СOVID-19 cases above 7100 pg/L h). principles actualize further investigation effects LIF/sLIFr complex associated infectious diseases.

Язык: Английский

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Circadian rhythms and cardiac physiology: An essential interplay

International review of cell and molecular biology, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Язык: Английский

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