Targeting Oxidative Stress and Inflammation to Prevent Ischemia-Reperfusion Injury

Frontiers in Molecular Neuroscience, Journal Year: 2020, Volume and Issue: 13

Published: March 5, 2020

The cerebral ischemia injury can result in neuronal death and/or functional impairment, which leads to further damage and dysfunction after recovery of blood supply. Cerebral ischemia/reperfusion (CIRI) often causes irreversible brain death, involves many complex pathological processes including oxidative stress, amino acid toxicity, the release endogenous substances, inflammation apoptosis. Oxidative stress are interactive play critical roles brain. is important process ischemic stroke for cascade development injury. caused by reactive oxygen species (ROS) during more likely lead cell ultimately reperfusion. During reperfusion especially, superoxide anion free radicals, hydroxyl nitric oxide (NO) produced, cause lipid peroxidation, Inflammation alters balance between pro-inflammatory anti-inflammatory factors Inflammatory therefore stimulate or exacerbate aggravate Neuroprotective therapies various stages response have received widespread attention. At present, neuroprotective drugs mainly include radical scavengers, agents, anti-apoptotic agents. However, molecular mechanisms interaction inflammation, their interplay with different types programmed unclear. a suitable method combination therapy has become hot topic.

Language: Английский

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CGRP and the Trigeminal System in Migraine

Headache The Journal of Head and Face Pain, Journal Year: 2019, Volume and Issue: 59(5), P. 659 - 681

Published: April 14, 2019

Objective The goal of this narrative review is to provide an overview migraine pathophysiology, with emphasis on the role calcitonin gene‐related peptide (CGRP) within context trigeminovascular system. Background Migraine a prevalent and disabling neurological disease that characterized in part by intense, throbbing, unilateral headaches. Despite recent advances understanding its still represents unmet medical need, as it often underrecognized undertreated. Although CGRP has been known play pivotal for last 2 decades, now received more interest spurred early clinical successes drugs block signaling Design This presents update PubMed searches were used find (ie, 2016 November 2018) published articles presenting new study results. Review are also included not primary references but bring these attention reader. Original research referenced describing core narrative, support ancillary points. Results trigeminal ganglion neurons connection between periphery, stemming from interface afferent fibers meningeal vasculature central terminals nucleus caudalis. neuropeptide abundant neurons, released peripheral nerve well being secreted ganglion. Release initiates cascade events include increased synthesis nitric oxide sensitization nerves. Secreted interacts adjacent satellite glial cells perpetuate sensitization, can drive second‐order neurons. A shift activity‐dependent activity‐independent may indicate mechanism driving progression episodic chronic migraine. pathophysiology cluster headache much obscure than migraine, emerging evidence suggests involve hypersensitivity Ongoing studies therapies targeted at will additional, valuable insights into disorder. Conclusions plays essential Treatments interfere functioning system effective against Blocking attenuating activity periphery be sufficient attack. Additionally, potential exists therapeutic strategy alleviate well.

Language: Английский

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`Cadmium induced cardiac inflammation in chicken (Gallus gallus) via modulating cytochrome P450 systems and Nrf2 mediated antioxidant defense

Chemosphere, Journal Year: 2020, Volume and Issue: 249, P. 125858 - 125858

Published: Feb. 7, 2020

Language: Английский

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NO as a multimodal transmitter in the brain: discovery and current status

British Journal of Pharmacology, Journal Year: 2018, Volume and Issue: 176(2), P. 197 - 211

Published: Nov. 7, 2018

NO operates throughout the brain as an intercellular messenger, initiating its varied physiological effects by activating specialized GC‐coupled receptors, resulting in formation of cGMP. In line with widespread expression this pathway, participates numerous different functions. This review gives account discovery a signalling molecule brain, experiments that originated search for mysterious cGMP‐stimulating factor released from central neurones when their NMDA receptors were stimulated, and summarizes subsequent key steps helped establish status transmitter. Currently, various modes operation are viewed to underlie diverse behaviour, ranging very local between synaptic partners (in orthograde or retrograde directions) volume‐type transmission whereby synthesized multiple synchronous sources summate spatially temporally influence intermingled neuronal non‐neuronal cells, irrespective anatomical connectivity. Linked Articles article is part themed section on Nitric Oxide 20 Years 1998 Nobel Prize. To view other articles visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.2/issuetoc

Language: Английский

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Nitric oxide signalling in the brain and its control of bodily functions

British Journal of Pharmacology, Journal Year: 2019, Volume and Issue: 177(24), P. 5437 - 5458

Published: July 26, 2019

Nitric oxide (NO) is a versatile molecule that plays key roles in the development and survival of mammalian species by endowing brain neuronal networks with ability to make continual adjustments function response moment‐to‐moment changes physiological input. Here, we summarize progress field argue NO‐synthetizing neurons NO signalling provide core hub for integrating sensory‐ homeostatic‐related cues, control bodily functions, potential target new therapeutic opportunities against several neuroendocrine behavioural abnormalities.

Language: Английский

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The Role of Endothelial Dysfunction in the Pathophysiology and Cerebrovascular Effects of Migraine: A Narrative Review

Journal of Clinical Neurology, Journal Year: 2021, Volume and Issue: 17(2), P. 164 - 164

Published: Jan. 1, 2021

Migraine is a complex neurovascular disorder whose triggers are not entirely understood. Endothelial dysfunction might play role in migraine, and there have been numerous reports on endothelium migraine pathophysiology, but their reciprocal cause-effect relationship remains unclear. This review the current evidence dysfunction, its link with possible consequences for cerebral hemodynamics.We performed systematic literature search of PubMed up to March 2020. We included 115 articles narrative review.Several studies demonstrated that may an important migraine. Despite lack specific biomarkers, oxidative stress inflammation-two primary causes endothelial damage-in The main increased vascular tone, thrombosis, inflammation, permeability. As consequence stress, activity endothelin-1 counterbalanced by nitric oxide (NO), levels decrease lead vasoconstriction contribution cortical spreading depression. NO involved pain perception via cyclic guanosine monophosphate (cGMP) pathway induction calcitonin gene-related peptide. Oxidative induce hypercoagulable state mainly affects platelet function through different mechanisms. seems be particularly pronounced aura (MA). involves intracranial vessels, since flow-mediated dilation cannot detect overt peripheral dysfunction.Endothelial risk marker. How it impacts MA, needs understood better defining increasing stroke patients.

Language: Английский

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The putative role of neuroinflammation in the complex pathophysiology of migraine: From bench to bedside

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 180, P. 106072 - 106072

Published: March 11, 2023

The implications of neurogenic inflammation and neuroinflammation in the pathophysiology migraine have been clearly demonstrated preclinical models involving several sites relevant trigemino-vascular system, including dural vessels trigeminal endings, ganglion, nucleus caudalis as well central pain processing structures. In this context, a role has attributed over years to some sensory parasympathetic neuropeptides, particular calcitonin gene neuropeptide, vasoactive intestinal peptide pituitary adenylate cyclase-activating polypeptide. Several clinical lines evidence also support implication potent vasodilator messenger molecule nitric oxide pathophysiology. All these molecules are involved vasodilation intracranial vasculature, peripheral sensitization system. At meningeal level, engagement immune cells innate immunity, mast-cells dendritic cells, their mediators, observed response neuropeptides release due system activation. context neuroinflammatory events implicated pathogenesis, activated glial structures nociceptive signals seem play role. Finally, cortical spreading depression, pathophysiological substrate aura, reported be associated with inflammatory mechanisms such pro-inflammatory cytokine upregulation intracellular signalling. Reactive astrocytosis consequent depression is linked an markers. present review summarizes current findings on roles responses possible exploitation view innovative disease-modifying strategies.

Language: Английский

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Practical Three-Component Regioselective Synthesis of Drug-Like 3-Aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines as Potential Non-Covalent Multi-Targeting Inhibitors To Combat Neurodegenerative Diseases

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(9), P. 1828 - 1881

Published: April 22, 2024

Neurodegenerative diseases (NDs) are one of the prominent health challenges facing contemporary society, and many efforts have been made to overcome (or) control it. In this research paper, we described a practical one-pot two-step three-component reaction between 3,4-dihydronaphthalen-1(2H)-one (1), aryl(or heteroaryl)glyoxal monohydrates (2a–h), hydrazine monohydrate (NH2NH2•H2O) for regioselective preparation some 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnoline derivatives (3a–h). After synthesis characterization mentioned cinnolines (3a–h), in silico multi-targeting inhibitory properties these heterocyclic scaffolds investigated upon various Homo sapiens-type enzymes, including hMAO-A, hMAO-B, hAChE, hBChE, hBACE-1, hBACE-2, hNQO-1, hNQO-2, hnNOS, hiNOS, hPARP-1, hPARP-2, hLRRK-2(G2019S), hGSK-3β, hp38α MAPK, hJNK-3, hOGA, hNMDA receptor, hnSMase-2, hIDO-1, hCOMT, hLIMK-1, hLIMK-2, hRIPK-1, hUCH-L1, hPARK-7, hDHODH, which confirmed their functions roles neurodegenerative (NDs), based on molecular docking studies, obtained results were compared with wide range approved drugs well-known (with IC50, EC50, etc.) compounds. addition, ADMET prediction analysis was performed examine prospective drug synthesized compounds The from studies ADMET-related data demonstrated that series heteroaryl)-5,6-dihydrobenzo[h]cinnolines especially hit ones, can really be turned into potent core new treatment and/or due having reactionable locations, they able further organic reactions (such as cross-coupling reactions), expansion (for example, using other types monohydrates) makes avenue designing novel efficient purpose.

Language: Английский

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Treating episodic migraine with precision: the evolving landscape of targeted therapies driven by insights in disease biology

Expert Opinion on Biological Therapy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15

Published: Jan. 20, 2025

Migraine is a disabling neurological disorder with complex neurobiology. It appears as cyclic of sensory processing, affecting multiple systems beyond nociception. Overlapping mechanisms, including dysfunctional processing input from brain structures are involved in the generation attacks. This review provides comprehensive synthesis on migraine neurobiology, which was additionally informed by search research databases (PubMed, ClinicalTrials.gov). Findings most recent literature integrated pathophysiological framework. By combining mechanistic insights and clinical trial data, this highlights trajectory precision medicine treatment, offering perspective near future targeted individualized therapeutic strategies. Recent advances neurobiology offer potential solutions to longstanding challenges. While CGRP therapies have shown promise addressing specific pathophysiology suggests that combination targeting pathways could be beneficial prevention. The growing diversity treatment options presents challenges therapy selection, underscoring need for predictive biomarkers. These innovations can optimize strategies improve patient outcomes. As field progresses, personalized, multimodal approaches poised become standard care, significantly advancing area.

Language: Английский

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β-blockers: Their new life from hypertension to cancer and migraine

Pharmacological Research, Journal Year: 2019, Volume and Issue: 151, P. 104587 - 104587

Published: Dec. 3, 2019

Language: Английский

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