Tryptophan metabolism and ischemic stroke: An intricate balance DOI Creative Commons
Chongjie Yao,

Dong Xie,

Yuchen Zhang

et al.

Neural Regeneration Research, Journal Year: 2025, Volume and Issue: 21(2), P. 466 - 477

Published: Jan. 13, 2025

Ischemic stroke, which is characterized by hypoxia and ischemia, triggers a cascade of injury responses, including neurotoxicity, inflammation, oxidative stress, disruption the blood–brain barrier, neuronal death. In this context, tryptophan metabolites enzymes, are synthesized through kynurenine 5-hydroxytryptamine pathways, play dual roles. The delicate balance between neurotoxic neuroprotective substances crucial factor influencing progression ischemic stroke. Neuroprotective metabolites, such as kynurenic acid, exert their effects various mechanisms, competitive blockade N-methyl-D-aspartate receptors, modulation α7 nicotinic acetylcholine scavenging reactive oxygen species. contrast, quinolinic acid can hinder development vascular glucose transporter proteins, induce neurotoxicity mediated species, disrupt mitochondrial function. Additionally, enzymes involved in metabolism major roles these processes. Indoleamine 2,3-dioxygenase pathway hydroxylase influence neuroinflammation brain homeostasis. Consequently, generated have substantial on Stroke treatment aims to restore metabolite levels; however, precise regulation within central nervous system remains challenge for Therefore, review aimed elucidate complex interactions stroke develop targeted therapies that neuroprotection.

Language: Английский

Microglial phagocytosis and regulatory mechanisms after stroke DOI
Weijie Chen, Yueman Zhang,

Xiaozhu Zhai

et al.

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2022, Volume and Issue: 42(9), P. 1579 - 1596

Published: May 1, 2022

Stroke, including ischemic stroke and hemorrhagic can cause massive neuronal death disruption of brain structure, which is followed by secondary inflammatory injury initiated pro-inflammatory molecules cellular debris. Phagocytic clearance debris microglia, the brain’s scavenger cells, pivotal for neuroinflammation resolution neurorestoration. However, microglia also exacerbate loss phagocytosing stressed-but-viable neurons in penumbra, thereby expanding area hindering neurofunctional recovery. Microglia constantly patrol central nervous system using their processes to scour environment start or cease phagocytosis progress depending on “eat me” “don’t eat me’’ signals surface. An optimal immune response requires a delicate balance between different phenotypic states regulate neuro-inflammation facilitate reconstruction after stroke. Here, we examine literature discuss molecular mechanisms pathways regulating microglial phagocytosis, resulting effects neural regeneration, as well potential therapeutic targets that might modulate phagocytic activity improve neurological function

Language: Английский

Citations

46
Astrocyte Involvement in Blood–Brain Barrier Function: A Critical Update Highlighting Novel, Complex, Neurovascular Interactions DOI Open Access
Doina Manu, Mark Slevin, Laura Bărcuțean

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(24), P. 17146 - 17146

Published: Dec. 5, 2023

Neurological disorders have been linked to a defective blood–brain barrier (BBB), with dysfunctions triggered by stage-specific disease mechanisms, some of these being generated through interactions in the neurovascular unit (NVU). Advanced knowledge molecular and signaling mechanisms NVU emergence improved experimental models allow BBB permeability prediction development new brain-targeted therapies. As constituents, astrocytes are most numerous glial cells, characterized heterogeneity that occurs as result developmental context-based gene expression profiles differential non-coding ribonucleic acids (RNAs). Due their dynamic responses different signals, may beneficial or detrimental role BBB’s function, deep effects on pathophysiology (and progression of) central nervous system diseases. The implication astrocytic-derived extracellular vesicles pathological due ability pass BBB, must also be considered. astrocytes’ interaction endothelial cells at level considered promising therapeutic targets neurological conditions. Nevertheless, personalized well-founded approach addressed, temporal spatial reactive astrogliosis states during disease.

Language: Английский

Citations

41
The central role of peripheral inflammation in ischemic stroke DOI
Molly Monsour, Cesar V. Borlongan

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2023, Volume and Issue: 43(5), P. 622 - 641

Published: Jan. 5, 2023

Stroke pathology and its treatments conventionally focus on the brain. Probing inflammation, a critical secondary cell death mechanism in stroke, has been largely relegated to To this end, peripheral inflammation emerged as an equally potent contributor onset progression of stroke death. Here, we review novel concepts organs displaying robust inflammatory response stroke. These inflammation-plagued include spleen, cervical lymph nodes, thymus, bone marrow, gastrointestinal system, adrenal glands, likely converging their effects through B T-cells. Recognizing significant impact systemic also discuss innovative therapeutics directed at sequestration inflammation. This paper challenges paradigm brain-centered disease treatment offers approach our understanding.

Language: Английский

Citations

27
Novel Multi-Antioxidant Approach for Ischemic Stroke Therapy Targeting the Role of Oxidative Stress DOI Creative Commons
Camilo Briones-Valdivieso,

Felipe Briones,

Sofía Orellana-Urzúa

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 501 - 501

Published: Feb. 23, 2024

Stroke is a major contributor to global mortality and disability. While reperfusion essential for preventing neuronal death in the penumbra, it also triggers cerebral ischemia-reperfusion injury, paradoxical injury primarily caused by oxidative stress, inflammation, blood–brain barrier disruption. An burst inflicts marked cellular damage, ranging from alterations mitochondrial function lipid peroxidation activation of intricate signalling pathways that can even lead cell death. Thus, given pivotal role stress mechanisms reinforcement antioxidant defence system has been proposed as protective approach. Although this strategy proven be successful experimental models, its translation into clinical practice yielded inconsistent results. However, should considered availability numerous molecules with wide range chemical properties affect extent injury; several groups molecules, including polyphenols, carotenoids, vitamins, among other compounds, mitigate damage intervening multiple at various stages. Multiple trials have previously conducted evaluate these using melatonin, acetyl-L-carnitine, chrysanthemum extract, edaravone dexborneol, saffron, coenzyme Q10, oleoylethanolamide, treatments. Therefore, multi-antioxidant therapy emerges promising novel therapeutic option due potential synergistic effect provided simultaneous roles individual compounds.

Language: Английский

Citations

14
Detrimental Roles of Hypoxia-Inducible Factor-1α in Severe Hypoxic Brain Diseases DOI Open Access
Yoon Kyung Choi

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4465 - 4465

Published: April 18, 2024

Hypoxia stabilizes hypoxia-inducible factors (HIFs), facilitating adaptation to hypoxic conditions. Appropriate hypoxia is pivotal for neurovascular regeneration and immune cell mobilization. However, in central nervous system (CNS) injury, prolonged severe harms the brain by triggering inflammation, oxidative stress, glial activation, vascular damage, mitochondrial dysfunction, death. Diminished improves cognitive function individuals with CNS injuries. This review discusses current evidence regarding contribution of injuries, an emphasis on HIF-1α-mediated pathways. During CNS, HIF-1α facilitates inflammasome formation, presents molecular mechanisms which involved pathogenesis such as stroke, traumatic Alzheimer’s disease. Deciphering will contribute development therapeutic strategies diseases.

Language: Английский

Citations

11
Adaptogens in Long-Lasting Brain Fatigue: An Insight from Systems Biology and Network Pharmacology DOI Creative Commons
Alexander Panossian,

Terrence Lemerond,

Thomas Efferth

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 261 - 261

Published: Feb. 15, 2025

Long-lasting brain fatigue is a consequence of stroke or traumatic injury associated with emotional, psychological, and physical overload, distress in hypertension, atherosclerosis, viral infection, aging-related chronic low-grade inflammatory disorders. The pathogenesis linked to disrupted neurotransmission, the glutamate-glutamine cycle imbalance, glucose metabolism, ATP energy supply, which are multiple molecular targets signaling pathways neuroendocrine-immune blood circulation systems. Regeneration damaged tissue long-lasting multistage process, including spontaneously regulating hypothalamus-pituitary (HPA) axis-controlled anabolic-catabolic homeostasis recover harmonized sympathoadrenal system (SAS)-mediated function, deregulated gene expression rehabilitation. driving mechanism spontaneous recovery regeneration cross-talk mediators neuronal, microglia, immunocompetent, endothelial cells collectively involved neurogenesis angiogenesis, plant adaptogens can target. Adaptogens small molecules origin that increase adaptability organisms stress by interaction HPA axis SAS (neuroendocrine-immune cardiovascular complex), targeting adaptive GPCR pathways. Two major groups comprise (i) phenolic phenethyl phenylpropanoid derivatives (ii) tetracyclic pentacyclic glycosides, whose chemical structure be distinguished as related correspondingly monoamine neurotransmitters (epinephrine, norepinephrine, dopamine) steroid hormones (cortisol, testosterone, estradiol). In this narrative review, we discuss multitarget integrated pharmacological activity botanical ischemic stroke, fatigue; time-dependent dual response physiological regulatory systems support overload; (iii) dose-dependent reversal (hormetic) effect adaptogens. This review shows adaptogenic concept cannot reduced rectified various effects on selected specific modes action without estimating their interactions within networks complex that, turn, regulates other (cardiovascular, gastrointestinal, reproductive systems) due numerous intra- extracellular communications feedback regulations. These result polyvalent pleiotropic adaptogens, essential for characterizing distinct types botanicals. They trigger defense leads extension limits resilience inducing mental For first time, justifies potential particularly hybrid preparation (BHP) Arctic Root Ashwagandha, providing rationale use individuals experiencing fatigue. provided insight into future research network pharmacology preventing rehabilitating following trauma, infections.

Language: Английский

Citations

1
Melatonin enhances neurogenesis and neuroplasticity in long-term recovery following cerebral ischemia in mice DOI
Merve Beker, Mustafa Çağlar Beker, Birsen Elibol

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(4), P. 167738 - 167738

Published: Feb. 22, 2025

Language: Английский

Citations

1
Beneficial and Detrimental Roles of Heme Oxygenase-1 in the Neurovascular System DOI Open Access
Yoon Kyung Choi, Young‐Myeong Kim

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(13), P. 7041 - 7041

Published: June 24, 2022

Heme oxygenase (HO) has both beneficial and detrimental effects via its metabolites, including carbon monoxide (CO), biliverdin or bilirubin, ferrous iron. HO-1 is an inducible form of HO that upregulated by oxidative stress, nitric oxide, CO, hypoxia, whereas HO-2 a constitutive regulates vascular tone homeostasis. In brains injured trauma, ischemia-reperfusion, Alzheimer’s disease (AD), the long-term expression can be detected, which lead to cytotoxic ferroptosis iron accumulation. contrast, transient induction in peri-injured region may have regenerative potential (e.g., angiogenesis, neurogenesis, mitochondrial biogenesis) neurovascular protective through CO-mediated signaling pathway, antioxidant properties iron-mediated ferritin synthesis. this review, we discuss dual roles metabolites various diseases, age-related macular degeneration, ischemia-reperfusion injury, traumatic brain Gilbert’s syndrome, AD.

Language: Английский

Citations

34
Quercetin mitigates depression-like behavior via the suppression of neuroinflammation and oxidative damage in corticosterone-induced mice DOI
Chenjie Ge, Shiliang Wang,

Xuqi Wu

et al.

Journal of Chemical Neuroanatomy, Journal Year: 2023, Volume and Issue: 132, P. 102313 - 102313

Published: July 17, 2023

Language: Английский

Citations

20
Network Pharmacology and Molecular Docking-Based Mechanism Study to Reveal the Protective Effect of Salvianolic Acid C in a Rat Model of Ischemic Stroke DOI Creative Commons
Yuting Yang,

Yu He,

Xiaoyu Wei

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 27, 2022

Salvianolic acid C (SAC) is a major bioactive component of Salvia miltiorrhiza Bunge (Danshen), Chinese herb for treating ischemic stroke (IS). However, the mechanism by which SAC affects IS has not yet been evaluated, thus network pharmacology integrated molecular docking strategy was performed to systematically evaluate its pharmacological mechanisms, were further validated in rats with cerebral ischemia. A total 361 potential SAC-related targets predicted SwissTargetPrediction and PharmMapper, 443 IS-related obtained from DisGeNET, DrugBank, OMIM, Therapeutic Target database (TTD) databases. hit 60 associated IS. By Gene ontology (GO) functional annotation Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment combined protein-protein interaction (PPI) cytoHubba plug-ins, nine related signaling pathways (proteoglycans cancer, PI3K-Akt pathway, Focal adhesion, etc.), 20 hub genes identified. Consequently, indicated that may interact (F2, MMP7, KDR, IGF1, REN, PPARG, PLG, ACE MMP1). Four target proteins (VEGFR2, MMP1, PPARγ IGF1) verified using western blot. This study comprehensively analyzed treatment SAC. The results blot also confirmed against mainly anti-inflammatory angiogenesis, provides reference us find explore effective anti-IS drugs.

Language: Английский

Citations

27