Neuronal Death Mechanisms and Therapeutic Strategy in Ischemic Stroke

Neuroscience Bulletin, Год журнала: 2022, Номер 38(10), С. 1229 - 1247

Опубликована: Май 5, 2022

Abstract Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability, which gravely burdens the global economy. Current relatively effective clinical treatments are limited to intravenous alteplase thrombectomy. Even so, patients still benefit little due short therapeutic window risk of ischemia/reperfusion injury. It is therefore urgent figure out neuronal death mechanisms following ischemic in order develop new neuroprotective strategies. Regarding pathogenesis, multiple pathological events trigger activation cell pathways. Particular attention should be devoted excitotoxicity, oxidative stress, inflammatory responses. Thus, this article, we first review principal underlying mediated these significant events, such as intrinsic extrinsic apoptosis, ferroptosis, parthanatos, pyroptosis, necroptosis, autophagic death. Then, further discuss possibility interventions targeting summarize present pharmacological achievements.

Язык: Английский

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Oxidative Stress in the Brain: Basic Concepts and Treatment Strategies in Stroke

Antioxidants, Год журнала: 2021, Номер 10(12), С. 1886 - 1886

Опубликована: Ноя. 25, 2021

The production of free radicals is inevitably associated with metabolism and other enzymatic processes. Under physiological conditions, however, are effectively eliminated by numerous antioxidant mechanisms. Oxidative stress occurs due to an imbalance between the elimination under pathological conditions. also ageing. brain prone oxidative damage because its high metabolic activity vulnerability ischemic damage. stress, thus, plays a major role in pathophysiology both acute chronic pathologies brain, such as stroke, traumatic injury or neurodegenerative diseases. goal this article summarize basic concepts significance pathologies, well discuss treatment strategies for dealing stroke.

Язык: Английский

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Oxidative Stress and Erectile Dysfunction: Pathophysiology, Impacts, and Potential Treatments

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(8), С. 8807 - 8834

Опубликована: Авг. 14, 2024

Erectile dysfunction (ED) is a prevalent condition affecting men’s sexual health, with oxidative stress (OS) having recently been identified as significant contributing causative factor. This narrative review aims to elucidate the role of OS in pathophysiology ED, focusing on impact, mechanisms, and potential therapeutic interventions. Key findings indicate that disrupts endothelial function nitric oxide (NO) signaling, crucial for erectile function. Various sources reactive oxygen species (ROS) their detrimental effects penile tissue are discussed, including aging, diabetes mellitus, hypertension, hyperlipidemia, smoking, obesity, alcohol consumption, psychological stress, hyperhomocysteinemia, chronic kidney disease, sickle cell disease. Major ROS, such NADPH oxidase, xanthine uncoupled NO synthase (eNOS), mitochondrial electron transport, identified. scavenged by these leading characterized reduced availability, impaired vasodilation, increased vascular tone, inflammation. ultimately results ED due decreased blood flow inability achieve or maintain an erection. Furthermore, ROS impact transmission nitrergic neurotransmitters causing death neurons reducing signaling neuronal (nNOS), exacerbating ED. Therapeutic approaches targeting OS, antioxidants lifestyle modifications, show promise ameliorating symptoms. The underscores need further research develop effective treatments, emphasizing interplay between health Integrating pharmacological non-pharmacological strategies could enhance clinical outcomes patients, advocating management treatment protocols improve patient quality life.

Язык: Английский

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N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1268 - 1268

Опубликована: Янв. 23, 2022

N-acetyl-aspartyl-glutamate (NAAG) is the most abundant dipeptide in brain, where it acts as a neuromodulator of glutamatergic synapses by activating presynaptic metabotropic glutamate receptor 3 (mGluR3). Recent data suggest that NAAG selectively localized to postsynaptic dendrites and works retrograde neurotransmitter. released response provides neuron with feedback mechanisms inhibit excessive signaling. A key regulator synaptically available rapid degradation extracellular enzyme carboxypeptidase II (GCPII). Increasing endogenous NAAG-for instance inhibiting GCPII-is promising treatment option for many brain disorders excitotoxicity plays role. The main effect occurs through increased mGluR3 activation thereby reduced release. In present review, we summarize transmitter role discuss involvement normal physiology. We further suggested roles various neurological psychiatric diseases therapeutic potential strategies aiming enhance levels.

Язык: Английский

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The Promise of Niacin in Neurology

Neurotherapeutics, Год журнала: 2023, Номер 20(4), С. 1037 - 1054

Опубликована: Апрель 21, 2023

Язык: Английский

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Potential Role of Natural Antioxidants in Countering Reperfusion Injury in Acute Myocardial Infarction and Ischemic Stroke

Antioxidants, Год журнала: 2023, Номер 12(9), С. 1760 - 1760

Опубликована: Сен. 13, 2023

Stroke and acute myocardial infarction are leading causes of mortality worldwide. The latter accounts for approximately 9 million deaths annually. In turn, ischemic stroke is a significant contributor to adult physical disability globally. While reperfusion crucial tissue recovery, it can paradoxically exacerbate damage through oxidative stress (OS), inflammation, cell death. Therefore, imperative explore diverse approaches aimed at minimizing ischemia/reperfusion injury enhance clinical outcomes. OS primarily arises from an excessive generation reactive oxygen species (ROS) and/or decreased endogenous antioxidant potential. Natural compounds counteract the mechanisms linked ROS. promising preclinical results, based on monotherapies, account protective effects against by ROS, translating these models into human applications has yielded controversial evidence. However, since wide spectrum antioxidants having chemical characteristics offers varied biological actions signaling pathways, multitherapy emerged as valuable therapeutic resource. Moreover, combination in holds potential synergistic effects. This study was designed with aim providing updated overview natural suitable preventing cerebral injuries.

Язык: Английский

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Tapping into Nature’s Arsenal: Harnessing the Potential of Natural Antioxidants for Human Health and Disease Prevention

Foods, Год журнала: 2024, Номер 13(13), С. 1999 - 1999

Опубликована: Июнь 25, 2024

Numerous natural antioxidants commonly found in our daily diet have demonstrated significant benefits for human health and various diseases by counteracting the impact of reactive oxygen nitrogen species. Their chemical properties enable a range biological actions, including antihypertensive, antimicrobial, anti-inflammatory, anti-fibrotic, anticancer effects. Despite promising outcomes from preclinical studies, ongoing debate persists regarding their reproducibility clinical models. This controversy largely stems lack understanding pharmacokinetic these compounds, coupled with predominant focus on monotherapies research, neglecting potential synergistic effects arising combining different antioxidants. study aims to provide an updated overview antioxidants, operating under hypothesis that multitherapeutic approach surpasses monotherapy efficacy. Additionally, this underscores importance integrating into diet, as they prevent onset progression diseases. To reinforce perspective, findings pertaining treatment prevention non-alcoholic fatty liver disease conditions associated ischemia reperfusion phenomena, myocardial infarction, postoperative atrial fibrillation, stroke, are presented key references.

Язык: Английский

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Research progress of natural products for the treatment of ischemic stroke

Journal of Integrative Neuroscience, Год журнала: 2022, Номер 21(1), С. 014 - 014

Опубликована: Янв. 28, 2022

Stroke is a leading cause of death and disability world-widely. The incidence rate stroke has been increasing due to the aging population lifestyle changes. At present, only drug approved by US Food Drug Administration (FDA) for treatment ischemic tissue plasminogen activator (t-PA), but its clinical application greatly limited because narrow time window bleeding risk. Natural products have long history being used in traditional medicine with good safety, making them an important resource development new drugs. Indeed, some natural can target variety pathophysiological processes related stroke, including oxidative stress, inflammation neuronal apoptosis. Therefore, high-efficiency, low-toxicity, safe cheap active substances from great significance improving alternatives patients stroke. This article reviews neuroprotective effects 33 compounds searching recent literature. Among them, puerarin, pinocembrin, quercetin, epigallocatechin-3-gallate (EGCG), resveratrol potential review will provide powerful reference screening value or synthesizing agents as lead compounds.

Язык: Английский

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Signaling pathways in brain ischemia: Mechanisms and therapeutic implications

Pharmacology & Therapeutics, Год журнала: 2023, Номер 251, С. 108541 - 108541

Опубликована: Окт. 1, 2023

Язык: Английский

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Novel diagnostic biomarkers of oxidative stress, ferroptosis, immune infiltration characteristics and experimental validation in ischemic stroke

Aging, Год журнала: 2024, Номер unknown

Опубликована: Янв. 9, 2024

Ischemic stroke (IS) is a prominent type of cerebrovascular disease leading to death and disability in an aging society closely related oxidative stress. Gene expression profiling (GSE222551) was derived from Expression Omnibus (GEO), 1934 stress (OS) genes were obtained the GeneCards database. Subsequently, we identified 149 differentially expressed OS (DEOSGs). Finally, PTGS2, FOS, RYR1 as diagnostic markers IS. Moreover, GSE16561 used validate DEOSGs. Two (PTGS2 FOS) significantly highly expressed, while lowly IS group. Remarkably, immune infiltration characteristics these three analyzed, found that mainly correlated with Mast cells activated, Neutrophils, Plasma cells, respectively. Next, intersected DEOSGs ferroptosis gene set, findings revealed only PTGS2 ferroptosis. High levels infarcted cortex middle cerebral artery occlusion (MCAO) rats confirmed by immunofluorescence (IF), western blotting (WB), Immunohistochemistry (IHC). Inhibition clearly improved neurological outcome decreasing infarct volume, problems, modified severity scores following compared controls. The protective effect silencing may be anti-oxidative In conclusion, this work provide new perspective for research IS, further based on breakthrough.

Язык: Английский

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