Ferroptosis as a mechanism of neurodegeneration in Alzheimer's disease

Journal of Neurochemistry, Год журнала: 2021, Номер 159(5), С. 804 - 825

Опубликована: Сен. 23, 2021

Alzheimer's disease (AD) is the most prevalent form of dementia, with complex pathophysiology that not fully understood. While β-amyloid plaque and neurofibrillary tangles define pathology disease, mechanism neurodegeneration uncertain. Ferroptosis an iron-mediated programmed cell death characterised by phospholipid peroxidation has been observed in clinical AD samples. This review will outline growing molecular evidence implicating ferroptosis pathogenesis AD, implications for disease-modifying therapies.

Язык: Английский

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Mechanisms of Dexmedetomidine in Neuropathic Pain

Frontiers in Neuroscience, Год журнала: 2020, Номер 14

Опубликована: Май 5, 2020

Dexmedetomidine is a new-generation, highly selective α2 adrenergic receptor agonist with large number of advantages, including its sedative and analgesic properties, ability to inhibit sympathetic nerves, reduced anesthetic dosage, hemodynamic stability, mild respiratory depression abilities improve postoperative recognition. Its safety effectiveness, as well provide certain degree comfort patients, make it useful adjuvant for wide range clinical applications. For example, dexmedetomidine commonly used in patients undergoing general anesthesia, also exerts effects during tracheal intubation or mechanical ventilation intensive care unit patients. In recent years, the deepening research on dexmedetomidine, drug still applied treatment spastic pain, myofascial neuropathic complex pain syndrome chronic headache multimodal analgesia. However, we must note that appropriateness patient dose selection should be given attention when using this drug; furthermore, observed adverse reactions such hypotension bradycardia. Therefore, effectiveness long-term use remain studied. addition, basic experimental studies have found can protect important organs, brain, heart, kidney, liver lung, through various mechanisms, anti-sympathetic effects, inhibition apoptosis oxidative stress reduction inflammatory response. Moreover, neuroprotective properties received most from scholars. Hence, review, mainly focus characteristics applications especially role nervous system relief pain.

Язык: Английский

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Recent Advances in the Clinical Value and Potential of Dexmedetomidine

Journal of Inflammation Research, Год журнала: 2021, Номер Volume 14, С. 7507 - 7527

Опубликована: Дек. 1, 2021

Dexmedetomidine, a highly selective α2-adrenoceptor agonist, has sedative, anxiolytic, analgesic, sympatholytic, and opioid-sparing properties induces unique sedative response which shows an easy transition from sleep to wakefulness, thus allowing patient be cooperative communicative when stimulated. Recent studies indicate several emerging clinical applications via different routes. We review recent data on dexmedetomidine studies, particularly exploring the varying routes of administration, experimental implications, effects, comparative advantages over other drugs. A search was conducted PubMed Web Science libraries for using combinations words "dexmedetomidine", "route administration", pharmacological effect. The current routes, application categories are presented. It functions by stimulating pre- post-synaptic α2-adrenoreceptors within central nervous system, leading hyperpolarization noradrenergic neurons, induction inhibitory feedback loop, reduction norepinephrine secretion, causing sympatholytic effect, in addition its anti-inflammation, induction, bowel recovery, sore throat effects. Compared with similar agonists, both pharmacodynamics advantage significantly greater α2:α1-adrenoceptor affinity ratio pharmacokinetic having shorter elimination half-life. In application, been reported present significant number benefits including safe sedation various surgical interventions, improvement intraoperative postoperative analgesia, compromised airways without respiratory depression, nephroprotection stability hypotensive hemodynamics, nausea vomiting shivering incidence, decrease blood loss. Although is promising, it still limited further research required enhance understanding properties, selection, dosage, adverse

Язык: Английский

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The neuroprotective effect of dexmedetomidine and its mechanism

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Сен. 20, 2022

Dexmedetomidine (DEX) is a highly selective α2 receptor agonist that routinely used in the clinic for sedation and anesthesia. Recently, an increasing number of studies have shown DEX has protective effect against brain injury caused by traumatic (TBI), subarachnoid hemorrhage (SAH), cerebral ischemia ischemia-reperfusion (I/R), suggesting its potential as neuroprotective agent. Here, we summarized effects several models neurological damage examined mechanism based on current literature. Ultimately, found mainly involved inhibition inflammatory reactions, reduction apoptosis autophagy, protection blood-brain barrier enhancement stable cell structures five way. Therefore, can provide crucial advantage recovery patients with injury. The purpose this study was to further clarify mechanisms therefore clinical management injuries.

Язык: Английский

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Effect of dexmedetomidine on postoperative cognitive dysfunction and inflammation in patients after general anaesthesia

Medicine, Год журнала: 2019, Номер 98(18), С. e15383 - e15383

Опубликована: Май 1, 2019

Neuroprotective effects of dexmedetomidine are reported in preclinical and clinical studies but evidence regarding the postoperative neurocognitive function is still unclear. This study performed a meta-analysis on outcomes which examined performance inflammatory factors to investigate cognitive dysfunction (POCD) inflammation patients after general anaesthesia.Literatures were searched several electronic databases selected by following precise inclusion criteria. We PubMed, EMBASE, Cochrane Library, China Academic Journals full-text database (CNKI), Google Scholar find randomized controlled trials (RCTs) influence POCD who had undergone anaesthesia. Two researchers independently screened literature, extracted data, evaluated quality methodology against exclusion Meta-analyses pooled ORs incidences mean differences assessment scores levels carried out subgroup analyses performed. Stata 12.0 was used conduct our meta-analysis.Twenty-six RCTs included. Compared with controls, perioperative treatment significantly reduced incidence (pooled = 0.59, 95% confidence interval (CI) 0.45-2.95) improved Mini-Mental State Examination (MMSE) score (standardized difference (SMD) 1.74, CI 0.43-3.05) first day. Furthermore, decreased IL-6 (SMD -1.31, -1.87-0.75, P < .001) TNF-α -2.14, -3.14-1.14, compared saline/comparators treatment. In stratified analysis surgical type, age, type control, region, also significant between dexmedetomidine- saline-treated patients.Perioperative associated better postoperatively comparison both saline controls comparator anaesthetics.

Язык: Английский

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Dexmedetomidine inhibits inflammatory response and autophagy through the circLrp1b/miR-27a-3p/Dram2 pathway in a rat model of traumatic brain injury

Aging, Год журнала: 2020, Номер 12(21), С. 21687 - 21705

Опубликована: Ноя. 4, 2020

Circular RNAs (circRNAs) have a regulatory function on inflammation and autophagy, of which rno-circRNA_010705 (circLrp1b) appears to be significantly up-regulated following traumatic brain injury (TBI). Dexmedetomidine (DEX) shows improvement effects in TBI by inhibiting NLRP3/caspase-1. However, whether circLrp1b plays critical roles DEX-mediated attenuation the underlying mechanisms remain unclear. After was established rats controlled cortical impact (CCI) cause trauma, they received an intracerebroventricular injection lentiviral vector, followed intraperitoneal DEX. Administration DEX ameliorated autophagy TBI, accompanied Dram2 down-regulated miR-27a-3p. promoted attenuating TBI-induced neurologic impairment, inflammation, reversed inhibition miR-27a-3p or overexpression. Mechanistically, northern blot luciferase reporter assays indicated that expression functioning as sponge for promote involved treatment. Collectively, this study demonstrated inhibits inflammatory response vivo through inactivation circLrp1b/miR-27a-3p/Dram2 signaling pathway.

Язык: Английский

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Dexmedetomidine: What’s New for Pediatrics? A Narrative Review

Journal of Clinical Medicine, Год журнала: 2020, Номер 9(9), С. 2724 - 2724

Опубликована: Авг. 24, 2020

Over the past few years, despite lack of approved pediatric labelling, dexmedetomidine’s (DEX) use has become more prevalent in clinical practice as well research trials. Its respiratory-sparing effects and bioavailability by various routes are only some valued features DEX. In recent years potential organ-protective DEX, with possibility for preserving neurocognitive function, put it forefront bench research. This comprehensive review focused on literature but presents relevant, supporting adult animal studies order to detail growing body around pharmacology, end-organ effects, alternative administration, synergetic applications, considerations future.

Язык: Английский

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Involvement of Microbiome Gut–Brain Axis in Neuroprotective Effect of Quercetin in Mouse Model of Repeated Mild Traumatic Brain Injury

NeuroMolecular Medicine, Год журнала: 2022, Номер 25(2), С. 242 - 254

Опубликована: Дек. 8, 2022

Язык: Английский

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Effects of inflammation and oxidative stress on postoperative delirium in cardiac surgery

Frontiers in Cardiovascular Medicine, Год журнала: 2022, Номер 9

Опубликована: Ноя. 22, 2022

The past decade has witnessed unprecedented medical progress, which translated into cardiac surgery being increasingly common and safe. However, complications such as postoperative delirium remain a major concern. Although the pathophysiological changes of after poorly understood, it is widely thought that inflammation oxidative stress may be potential triggers delirium. development following associated with perioperative risk factors. Multiple interventions are explored to prevent treat Therefore, research on role biomarkers in well identification factors pharmacological necessary mitigate

Язык: Английский

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Neuro-Inflammation Modulation and Post-Traumatic Brain Injury Lesions: From Bench to Bed-Side

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(19), С. 11193 - 11193

Опубликована: Сен. 23, 2022

Head trauma is the most common cause of disability in young adults. Known as a silent epidemic, it can mosaic symptoms, whether neurological (sensory-motor deficits), psychiatric (depressive and anxiety symptoms), or somatic (vertigo, tinnitus, phosphenes). Furthermore, cranial (CT) children presents several particularities terms epidemiology, mechanism, physiopathology-notably linked to attack an immature organ. As adults, head have lifelong repercussions social family isolation, difficulties at school, and, later, socio-professional adversity. Improving management pre-hospital rehabilitation course these patients reduces secondary morbidity mortality, but often not without long-term disability. One hypothesized contributor this process chronic neuroinflammation, which could accompany primary lesions facilitate their development into tertiary lesions. Neuroinflammation complex involving different actors such glial cells (astrocytes, microglia, oligodendrocytes), permeability blood-brain barrier, excitotoxicity, production oxygen derivatives, cytokine release, tissue damage, neuronal death. Several studies investigated effect various treatments on neuroinflammatory response traumatic brain injury vitro animal human models. The aim review examine anti-inflammatory therapies that been implemented.

Язык: Английский

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