Downregulation of SIRT1, SIRT3, and IGF-1 in ApoE-deficient mice exacerbates neuronal damage induced by chronic cerebral hypoperfusion DOI Creative Commons
O. Yu. Harmatina,

К.В. Розова,

T. Y. Voznesenska

et al.

Regulatory Mechanisms in Biosystems, Journal Year: 2023, Volume and Issue: 14(3), P. 341 - 348

Published: June 30, 2023

Chronic cerebral hypoperfusion is a widespread pathological condition caused by chronically reduced blood flow leading to brain damage, but the specific molecular mechanisms that regulate these phenomena remain poorly understood. In this study, we investigated damage and neuronal DNA injury in vulnerable region of brain, hippocampus, as well involvement apolipoprotein E (ApoE), sirtuins 1 (SIRT1) 3 (SIRT3) types insulin-like growth factor (IGF-1) pathogenetic mice with chronic permanent occlusion left unilateral common carotid artery. Male C57/6j (C57, wild type) ApoE(-/-) were divided into four experimental groups (10 per group): sham-operated С57, С57 hypoperfusion, mice, hypoperfusion. Our results showed number damaged neurons hippocampus at 8 weeks after surgical manipulation increased both more pronounced rates than C57 mice. However, ApoE deficiency moderate was accompanied higher level undamaged (class 0) low maximally 4) cell nuclei contrast group C57. ApoE-deficient expression SIRT1, SIRT3, IGF-1 found. preserved, significantly comparison The obtained indicate leads downregulation SIRT3 brain; lack cytoprotection enhanced may participate damage.

Language: Английский

Farrerol alleviates cognitive impairments in chronic cerebral hypoperfusion via suppressing NLRP3 inflammasome-mediated pyroptosis DOI
Jie Zhang, Yaxuan Zhang, Yueqi Zhang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 153, P. 114442 - 114442

Published: March 19, 2025

Language: Английский

Citations

1
NLRP3 inflammasome in cognitive impairment and pharmacological properties of its inhibitors DOI Creative Commons

Yi Xu,

Yanling Yang, Xi Chen

et al.

Translational Neurodegeneration, Journal Year: 2023, Volume and Issue: 12(1)

Published: Nov. 2, 2023

Abstract Cognitive impairment is a multifactorial and multi-step pathological process that places heavy burden on patients the society. Neuroinflammation one of main factors leading to cognitive impairment. The inflammasomes are multi-protein complexes respond various microorganisms endogenous danger signals, helping initiate innate protective responses in inflammatory diseases. NLRP3 produce proinflammatory cytokines (interleukin IL-1β IL-18) by activating caspase-1. In this review, we comprehensively describe structure functions inflammasome. We also explore intrinsic relationship between inflammasome impairment, which involves immune cell activation, apoptosis, oxidative stress, mitochondrial autophagy, neuroinflammation. Finally, antagonists as targeted therapies improve

Language: Английский

Citations

18
The role of pyroptosis in cognitive impairment DOI Creative Commons

Xin Yang,

Zhe Tang

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: June 2, 2023

Cognitive impairment is a major global disease, manifests as decline in cognitive functioning and endangers the health of population worldwide. The incidence has increased rapidly with an increasingly aging population. Although mechanisms have partly been elucidated development molecular biological technology, treatment methods are very limited. As unique form programmed cell death, pyroptosis highly pro-inflammatory closely associated progression impairment. In this review, we discuss briefly research progress on relationship between its potential therapeutic values, to provide reference for field

Language: Английский

Citations

11
Neurobiological Mechanisms Underlying Psychological Dysfunction After Brain Injuries DOI Creative Commons

Prashin Unadkat,

Tania Rebeiz,

Erum Ajmal

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 74 - 74

Published: Jan. 8, 2025

Despite the presentation of similar psychological symptoms, dysfunction secondary to brain injury exhibits markedly lower treatment efficacy compared injury-independent dysfunction. This gap remains evident, despite extensive research efforts. review integrates clinical and preclinical evidence provide a comprehensive overview neurobiological mechanisms underlying neuropsychological disorders, focusing on role key regions in emotional regulation across various forms injuries. It examines therapeutic interventions mechanistic targets, with primary goal identifying pathways for targeted treatments. The highlights promising avenues addressing injury-associated dysfunction, emphasizing Nrf2, neuropeptides, nonpharmacological therapies as multi-mechanistic capable modulating upstream mediators address complex interplay factors injury. Additionally, it identifies sexually dimorphic potential areas further exploration advocates detailed investigations into sex-specific patterns uncover additional contributors these disorders. Furthermore, underscores significant gaps, particularly inadequate consideration interactions among causal factors, environmental influences, individual susceptibilities. By this provides new insights calls paradigm shift toward more context-specific integrative approach developing following

Language: Английский

Citations

0
Toll-Like Receptor 4-Mediated Neuroinflammation: Updates on Pathological Roles and Therapeutic Strategies in Chronic Cerebral Hypoperfusion DOI

Nuttapong Yawoot,

Jiraporn Tocharus, Chainarong Tocharus

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Language: Английский

Citations

0
AIM2 exacerbates hypoxic-ischemic brain damage in neonatal rats via promoting neuronal pyroptosis DOI Creative Commons
Qianqian Li, Zhou Wang,

Fengli Li

et al.

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: 224, P. 111305 - 111305

Published: March 16, 2025

Pyroptosis has been reported to play a pathogenic role in neonatal hypoxic-ischemic brain damage (HIBD). Absence melanoma 2 (AIM2) is an inflammasome involved pyroptosis. This study aimed investigate the of AIM2 hypoxic-ischemia (HI)-induced pyroptosis and rat HIBD model. In vivo, we injected lentivirus that overexpressed or knocked down into lateral ventricle rats within 24h after birth prepared 7-day Sprague Dawley (SD) vitro, transfected lentiviruses overexpressing knocking cultured primary neurons established oxygen/glucose deprivation/reoxygenation (OGD/R) 2,3,5-triphenyltetrazolium chloride (TTC) staining was used determine infarct size. Hematoxylin eosin Nissl were evaluate morphological changes damaged brain. Cell Counting Kit-8 (CCK-8) lactate dehydrogenase (LDH) assays cell viability toxicity. observed using transmission electron microscopy. expression significantly increased HI-induced cortex rats. Lentivirus-mediated overexpression aggravates injury OGD/R-induced neuronal vivo vitro. The lentivirus-mediated knockdown reversed these adverse effects. addition, whereas suppressed via AIM2/Caspase-1/GSDMD pathway. These findings show upregulation activates plays HIBD.

Language: Английский

Citations

0
The Bidirectional Role of Hypoxia-Inducible Factor 1 Alpha in Vascular Dementia Caused by Chronic Cerebral Hypoperfusion DOI

Phakkawat Thangwong,

Chainarong Tocharus, Jiraporn Tocharus

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Language: Английский

Citations

0
The Cooperation of Neurogranin with Calmodulin Promotes the Treatment of Aging-Related Diseases via Regular Exercise DOI

Hosniyeh Rajavand,

Vahideh Zalouli,

Zeinab Nematollahi

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 26, 2025

Language: Английский

Citations

0
B355252 Suppresses LPS-Induced Neuroinflammation in the Mouse Brain DOI Creative Commons

Qingping He,

Qi Qi, Gordon C. Ibeanu

et al.

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(5), P. 467 - 467

Published: May 7, 2024

B355252 is a small molecular compound known for potentiating neural growth factor and protecting against neuronal cell death induced by glutamate in vitro cerebral ischemia vivo. However, its other biological functions remain unclear. This study aims to investigate whether suppresses neuroinflammatory responses the brain. C57BL/6j mice were intraperitoneally injected with single dosage of lipopolysaccharide (LPS, 1 mg/kg) induce inflammation. (1 intervention was started two days prior LPS injection. The animal behavioral changes assessed pre- post-LPS injections. brains harvested at 4 24 h injection, histological, biochemical, cytokine array outcomes examined. Results showed that improved LPS-induced deterioration, mitigated brain tissue damage, suppressed activation microglial astrocytes. Furthermore, reduced protein levels key pyroptotic markers TLR4, NLRP3, caspase-1 inhibited increases IL-1β, IL-18, cytokines. In conclusion, demonstrates potent anti-neuroinflammatory effect vivo, suggesting potential therapeutic value warrants further investigation.

Language: Английский

Citations

3
Endothelial progenitor cell-derived conditioned medium mitigates chronic cerebral ischemic injury through macrophage migration inhibitory factor-activated AKT pathway DOI Creative Commons

Ya‐Wen Cheng,

Lingyu Yang, Yi‐Tzu Chen

et al.

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 14, 2024

Abstract Background Chronic cerebral ischemia (CCI) is a significant health issue characterized by hypoperfusion due to damage or occlusion of the carotid arteries. CCI may lead progressive cognitive impairment that considered as prelude neurodegenerative diseases, including dementia and Alzheimer's disease (AD). Endothelial progenitor cells (EPCs) have been implicated in vascular repair ischemic cerebrovascular primarily differentiating into endothelial (ECs) through paracrine effects. However, clinical transplantation stem cell therapies remains limited. In this study, we investigated effects EPC-derived conditioned medium (EPC-CM) on impaired vasculature neurological function rodent model mechanism involved. Methods EPC-CM was analyzed cytokine array identify key factors involved angiogenesis cellular senescence. The candidate were validated vitro using oxygen–glucose deprivation (OGD)-injured ECs EPCs. therapeutic identified factor further examined rat CCI, which induced bilateral internal artery ligation (BICAL). administered via intracisternal injection one week post BICAL. microvasculature neurobehavior rats three weeks after Results Macrophage migration inhibitory (MIF) EPC-CM. Recombinant MIF protein promoted prevented senescence injured EPCs ECs. effect similar These diminished when co-treated with MIF-specific antibody (Ab). Additionally, vascular, motor, improvements observed BICAL treated abolished Ab. Furthermore, found anti-senescence activating AKT pathway. Inhibition pathway protective study. Conclusions We demonstrated protected brain from chronic injury functional recovery MIF-mediated findings suggest holds potential novel cell-free approach for treating actions MIF.

Language: Английский

Citations

1