Oligodendrocytes Play a Critical Role in White Matter Damage of Vascular Dementia DOI Creative Commons
Hexin Zhang,

Yan-Rong Yang,

Jingjing Zhang

et al.

Neuroscience, Journal Year: 2023, Volume and Issue: 538, P. 1 - 10

Published: Oct. 31, 2023

With the deepening of population aging, treatment cognitive impairment and dementia is facing increasing challenges. Vascular (VaD) a dysfunction caused by brain blood flow damage one most common causes after Alzheimer's disease. White matter in patients with chronic ischemic often occurs before impairment, its pathological changes include leukoaraiosis, myelin destruction oligodendrocyte death. The pathophysiology vascular complex, involving variety neuronal lesions. current proposed mechanisms calcium overload, oxidative stress, nitrative stress inflammatory damage, which can lead to hypoxia-ischemia demyelination. Oligodendrocytes are only myelinating cells central nervous system closely associated VaD. In this review article, we intend further discuss role oligodendrocytes white injury VaD development anti-myelin target drugs.

Language: Английский

Pathophysiology of blood brain barrier dysfunction during chronic cerebral hypoperfusion in vascular cognitive impairment DOI Creative Commons

Vismitha Rajeev,

David Y. Fann,

Quynh Nhu Dinh

et al.

Theranostics, Journal Year: 2022, Volume and Issue: 12(4), P. 1639 - 1658

Published: Jan. 1, 2022

The prevalence of cerebrovascular disease increases with age, placing the elderly at a greater lifetime risk for dementia. Vascular cognitive impairment (VCI) encompasses spectrum deficits from mild to VCI and its most severe form, vascular dementia (VaD), is becoming major public health concern worldwide. As growing efforts are being taken understand VaD in animal models humans, pathogenesis actively explored. It postulated that chronic cerebral hypoperfusion (CCH) cause VCI. CCH activates molecular cellular injury cascade leads breakdown blood brain barrier (BBB) neurodegeneration. BBB tightly regulates movement substances between brain, thereby regulating microenvironment within parenchyma. Here we illustrate how damage causal through increased activation pathways related excitotoxicity, oxidative stress, inflammation matrix metalloproteinases lead downstream perivascular damage, leukocyte infiltration white matter changes brain. Thus, CCH-induced may initiate contribute vicious cycle, resulting progressive neuropathological This review outlines mechanisms govern during highlights clinical evidence identifying at-risk patients.

Language: Английский

Citations

162
Viruses and neurodegeneration: a growing concern DOI Creative Commons
Samia A. Shouman,

Nadine Hesham,

Tamer Z. Salem

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 12, 2025

Abstract Neurodegenerative diseases (NDDs) cause a progressive loss of neurons. Since NDDs are multifactorial, the precise etiology varies on basis type disease and patient history. Cohort studies case have demonstrated potential link between viral infections onset or progression NDDs. Recent findings concerning mechanisms by which neuropathic occur provided more insights into importance such connections. In this review, we aim to elaborate occurrence effects viruses from epidemiological, clinical, biological perspectives while highlighting treatments challenges. One key players in neuropathogenesis is neuroinflammation caused immune response virus; can due both neurotropic nonneurotropic viruses. The COVID-19 pandemic has raised concerns about whether vaccines essential for preventing may play part exacerbating accelerating By classifying common associated with them further delving their cellular pathways, review provides advance development diagnostic methods. Graphical

Language: Английский

Citations

1
Synaptic plasticity and neuroprotection: The molecular impact of flavonoids on neurodegenerative disease progression DOI

Spandana Rajendra Kopalli,

Tapan Behl,

Ashishkumar Kyada

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: 569, P. 161 - 183

Published: Feb. 7, 2025

Language: Английский

Citations

1
Interaction between Alzheimer’s Disease and Cerebral Small Vessel Disease: A Review Focused on Neuroimaging Markers DOI Open Access

Si Eun Kim,

Hee Jin Kim, Hyemin Jang

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10490 - 10490

Published: Sept. 10, 2022

Alzheimer's disease (AD) is characterized by the presence of β-amyloid (Aβ) and tau, subcortical vascular cognitive impairment (SVCI) cerebral small vessel (CSVD). They are most common causes in elderly population. Concurrent CSVD burden more commonly observed AD-type dementia than other neurodegenerative diseases. Recent developments Aβ tau positron emission tomography (PET) have enabled investigation relationship between AD biomarkers vivo. In this review, we focus on interaction markers clinical effects these two based molecular imaging studies. First, cover frequency markers, including patients with SVCI. Second, discuss potential distinct pathobiology SVCI compared to dementia. Next, SVCI, hemorrhagic amyloid angiopathy. Finally, review provides both current challenges future perspectives for

Language: Английский

Citations

24
Dl‐3‐n‐butylphthalide promotes synaptic plasticity by activating the Akt/ERK signaling pathway and reduces the blood–brain barrier leakage by inhibiting the HIF‐1α/MMP signaling pathway in vascular dementia model mice DOI Creative Commons

Ping Che,

Juan Zhang, Mingqian Yu

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(5), P. 1392 - 1404

Published: Feb. 8, 2023

Abstract Aims DL‐3‐n‐butylphthalide (NBP) exerts beneficial effects on global cognitive functions, but the underlying molecular mechanisms are still poorly understood. The present study aimed to investigate whether NBP mediates synaptic plasticity and blood–brain barrier (BBB) function, which play a pivotal role in pathogenesis of vascular dementia (VaD), mouse model bilateral common carotid artery stenosis (BCAS). Methods was administered mice at dose 80 mg/kg by gavage for 28 days after surgery. Cognitive function evaluated behavioral tests, hippocampal vivo electrophysiological recording. Cerebral blood flow (CBF), volume, white matter integrity were measured with laser speckle imaging (LSI) MRI. In addition, BBB leakage expression proteins related Akt/ERK HIF‐1α/MMP signaling pathways assessed biochemical assays. Results treatment alleviated impairment, atrophy, impairment induced BCAS. increased CBF, promoted integrity, decreased leakage. Regarding mechanisms, BCAS, may activate pathway, upregulates synapse‐associated proteins, it also inhibit thereby increasing tight junction (TJ) proteins. Conclusion conclusion, our results demonstrated therapeutic improving via wide range targets subjected

Language: Английский

Citations

15
Edaravone dexborneol attenuates cognitive impairment in a rat model of vascular dementia by inhibiting hippocampal oxidative stress and inflammatory responses and modulating the NMDA receptor signaling pathway DOI Creative Commons
Hui Guo, Haodong Li, Zhisheng Jia

et al.

Brain Research, Journal Year: 2024, Volume and Issue: 1833, P. 148917 - 148917

Published: April 4, 2024

Exploring the intricate pathogenesis of Vascular Dementia (VD), there is a noted absence potent treatments available in current medical landscape. A new brain-protective medication developed China, Edaravone dexboeol (EDB), has shown promise due to its antioxidant and anti-inflammatory properties, albeit with need for additional research elucidate role mechanisms VD contexts. In setup, model was established utilizing Sprague-Dawley (SD) rats, subjected permanent bilateral typical carotid artery occlusion (2VO). Behavioral assessment rats conducted using Bederson test pole climbing test, while cognitive abilities, particularly learning memory, were evaluated via novel object recognition Morris water maze test. Ensuing, levels malondialdehyde (MDA), superoxide dismutase (SOD), IL-1β, IL-6, IL-4, tumor necrosis factor-α (TNF-α) determined through Enzyme-Linked Immunosorbent Assay (ELISA). Synaptic plasticity-related proteins, synaptophysin (SYP), post-synaptic density protein 95 (PSD-95), N-methyl-D-aspartate (NMDA) receptor proteins (NR1, NR2A, NR2B) investigated Western blotting technique. The findings imply that EDB potential ameliorate deficiencies, attributed VD, by mitigating oxidative stress, dampening inflammatory responses, modulating NMDA signaling pathway, furnishing perspectives into EDB's mechanism proposing avenues therapeutic strategies managing VD.

Language: Английский

Citations

6
Air pollution: a latent key driving force of dementia DOI Creative Commons
Mahdiyeh Mohammadzadeh, Amir Hossein Khoshakhlagh, Jordan Grafman

et al.

BMC Public Health, Journal Year: 2024, Volume and Issue: 24(1)

Published: Sept. 2, 2024

Many researchers have studied the role of air pollutants on cognitive function, changes in brain structure, and occurrence dementia. Due to wide range studies often contradictory results, present systematic review was conducted try clarify relationship between To identify for this review, a search Scopus, PubMed, Web Science databases (without historical restrictions) until May 22, 2023. The PECO statement created research question, articles that did not meet criteria were excluded. In animal studies, laboratory books, articles, conference papers letters editors avoided. Also, focused effect cellular biochemical investigating dementia) also A quality assessment done according type design each article, using checklist developed by Joanna Briggs Institute (JBI). Finally, selected reviewed discussed terms Alzheimer's dementia non-Alzheimer's We identified 14,924 through databases, after comprehensive reviews, 53 found be eligible inclusion current review. results showed chronic exposure higher levels associated with adverse effects abilities presence Studies strongly supported negative PM2.5 then NO2 development neurodegenerative disorders old age. Because onset structural due begins decades before disease symptoms, pollution is considered modifiable risk factor, taking preventive measures reduce introducing behavioral interventions people's advisable.

Language: Английский

Citations

6
Danggui-Shaoyao San Alleviates Cognitive Impairment via Enhancing HIF-1α/EPO Axis in Vascular Dementia Rats DOI

Yuan Ningning,

Ying Xu, Xiang Li

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 331, P. 118306 - 118306

Published: May 7, 2024

Language: Английский

Citations

5
Inhibition of ADORA3 promotes microglial phagocytosis and alleviates chronic ischemic white matter injury DOI Creative Commons
Yuhao Xu,

Limoran Tang,

Chao Zhou

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(5)

Published: May 1, 2024

Abstract Background Adenosine A3 receptor (ADORA3) belongs to the adenosine families and role of ADORA3 in vascular dementia (VaD) is largely unexplored. The present study sought determine therapeutic antagonist a mouse model VaD. Methods GSE122063 dataset was selected screen differential expression genes pathways between VaD patients controls. A bilateral carotid artery stenosis (BCAS) established. cognitive functions were examined by novel object recognition test, Y maze fear conditioning test. white matter injury (WMI) 9.4 T MRI, western blot, immunofluorescence staining. mechanisms ADORA3‐regulated phagocytosis microglia using qPCR, dual staining, flow cytometry. Results elevated brain tissues indicated as key gene for GSE122063. In BCAS mice, predominantly corpus callosum. promotes microglial myelin debris facilitating cAMP/PKA/p‐CREB pathway thereby ameliorates WMI impairment mice. effect partially reversed inhibition cAMP/PKA pathway. Conclusions alleviates chronic ischemic modulating clearance microglia, which may be potential target treatment

Language: Английский

Citations

5
Tilianin improves cognition in a vascular dementia rodent model by targeting miR-193b-3p/CaM- and miR-152-3p/CaMKIIα-mediated inflammatory and apoptotic pathways DOI Creative Commons
Ting Sun,

Linjie Tan,

Mimin Liu

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 19, 2023

Introduction Although vascular dementia (VaD) is the second most prevalent form of dementia, there currently a lack effective treatments. Tilianin, isolated from traditional drug Dracocephalum moldavica L., may protect against ischemic injury by inhibiting oxidative stress and inflammation via CaMKII-related pathways but with weak affinity CaMKII molecule. microRNAs (miRNAs), functioning in post-transcriptional regulation gene expression, play role pathological process VaD cognitive impairment, neuroinflammatory response, neuronal dysfunction. This study aimed to investigate tilianin therapy underlying mechanism through which regulates signaling based on miRNA-associated transcriptional action. Methods Rats 2-vessel occlusion (2VO), standard model VaD, were treated tilianin, vehicle control, target overexpression or downregulation. High-throughput sequencing, qRT-PCR, western blot analyses utilized identify downstream genes involved VaD. Results Our results showed that ameliorated deficits, neurodegeneration, microglial astrocytic activation rats 2VO. Subsequent high-throughput sequencing qRT-PCR revealed increased downregulated miR-193b-3p miR-152-3p levels cortex hippocampus 2VO rats. Mechanistically, targeting CaM CaMKIIα identified VaD-associated pathology, p38 MAPK/NF--κB p65 pathway decreasing TNF-α IL-6 levels. Further gain- loss-of-function experiments for these key tilianin-exerted improvement activating Bcl-2/Bax/caspase-3/PARP brain was abolished inhibition. Moreover, eliminated elevated effects tilianin’s protection inflammatory reactions apoptotic signaling. Discussion Together, findings indicate improves cognition regulating miR-193b-3p/CaM- miR-152-3p/CaMKIIα-mediated pathways, suggesting potential small-molecule regulator miRNA associated treatment.

Language: Английский

Citations

13