Models and mechanisms of vascular dementia

Venkat, Poornima; Chopp, Michael; Chen, Jieli

doi:10.1016/j.expneurol.2015.05.006

Cited by 267 publications

(290 citation statements)

References 164 publications

(174 reference statements)

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“…Okvarjeno mora biti najmanj eno kognitivno področje po možgan-skem žilnem dogodku (neodvisno od motornih ali senzornih primanjkljajev po možganski kapi). Področja, ki jih ocenjujemo so spomin, pozornost, izvršilne funkcije, jezik in govorno izražanje ter vidno-prostorsko procesiranje (6,7,11,12).…”

Section: Uvodunclassified

“…Eden glavnih dejavnikov je ateroskleroza, ki prizadene predvsem velike in srednje velike arterije Willisovega kroga (16). Tromboze teh žil ali tromboembolije manjših po rupturi aterosklerotičnega plaka vodijo do možganske hipoperfuzije in zato VaKU (12). Druga pogosta dejavnika tveganja sta atrijska fibrilacija in bolezen karotidnih arterij (12).…”

Section: Dejavniki Tveganjaunclassified

“…Tromboze teh žil ali tromboembolije manjših po rupturi aterosklerotičnega plaka vodijo do možganske hipoperfuzije in zato VaKU (12). Druga pogosta dejavnika tveganja sta atrijska fibrilacija in bolezen karotidnih arterij (12).…”

Section: Dejavniki Tveganjaunclassified

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Vaskularni kognitivni upad in vaskularna demenca

Štante

Potočnik

Rakuša³

2017

SlovMedJour

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IzvlečekV razvitem svetu ima 5-10 % prebivalstva nad 65 let demenco, katere pojavnost še vedno narašča. Demence zaradi možganskih žilnih bolezni -vaskularna demenca (VaD) predstavljajo dobro petino vseh vzrokov za demenco. Milejša oblika je vaskularni kognitivni upad (VaKU). Za postavitev diagnoze VaD je pomembno, da sta upad spoznavnih sposobnosti in možgansko-žilna bolezen jasno časovno povezana ter ni popravljivih vzrokov za kognitivni upad. Pri postavitvi diagnoze uporabimo nevropsihološko testiranje in slikovne preiskave.Glavni dejavniki tveganja za VaKU in VaD so starost, ateroskleroza, sladkorna bolezen in arterijska hipertenzija, ki sprožijo kaskado dogodkov v patogenezi kognitivne okvare. Ta je zelo raznolika in poteka z ali brez pridruženih nevroloških simptomov. Klinična slika je odvisna od področja in velikosti možganske spremembe.Pri zdravljenju VaKU in VaD je najbolj pomembna primarna preventiva. Za zdravljenje simptomov VaKU in VaD se uporabljajo enaka zdravila kot za zdravljenje simptomov Alzheimerjeve bolezni. Pomembni sta še rehabilitacija in sekundarna preventiva ponovne možganske kapi. AbstractIn the developed world, five to ten percent of people older than 65 years have dementia. One fifth of dementia etiologies are due to vascular brain lesions (VaD -vascular dementia). A milder form is called vascular cognitive impairment (VCI). The main clinical criteria for VaD are: 1. cognitive decline verified with standardized cognitive test/scale, 2. evidence of the associated vascular brain lesion, 3. excluded reversible causes of cognitive decline.The main risk factors for VaD are age, atherosclerosis, diabetes and hypertension. They play a key role in pathogenesis of the cognitive impairment. Depending on the damaged brain region, different cognitive domains may be affected with or without other neurological signs. These diversities in the clinical picture challenge the correct diagnosis. Unique feature of VaD is its progression, which can be stopped, if patients receive an appropriate treatment.The treatment of VCI and VaD symptoms is similar to that in Alzheimer's disease. More importantly, VCI may be slowed down or even stopped with proper secondary stroke prevention and good rehabilitation. The most efficient is primary stroke prevention with healthy lifestyle and treatment of acquired risk factors.

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Section: Uvodunclassified

Section: Dejavniki Tveganjaunclassified

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Vaskularni kognitivni upad in vaskularna demenca

Štante

Potočnik

Rakuša³

2017

SlovMedJour

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“…CCH is a common consequence of various cerebral vascular disorders and hemodynamic changes that contributes to the risk of VaD. In rodents, the bilateral common carotid artery occlusion (2VO) model is so far the most effective and frequently-used experimental model to evaluate the relation between chronic cerebral hypoperfusion and vascular diseaserelated dementia [2,[5][6][7]. However, the progress on understanding the basis of the disease and developing treatments is not encouraging.…”

Section: Reviewmentioning

confidence: 99%

“…It is a progressive disease caused by cerebrovascular diseases with the pathologic features of reduced blood flow in the brain that affects cognitive abilities [2][3][4]. Accordingly, the cognitive impairment associated with vessel disorders is an increasingly important and recognised area of the medicine of VaD patients.…”

Section: Reviewmentioning

confidence: 99%

HCN Channels: From the Role in Chronic Cerebral Hypoperfusion-Induced Cognitive Impairments to a New Therapeutic Target for Vascular Dementia

Luo¹,

Guo

2015

J Neurol Neurophysiol

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Hyperpolarization-activated cyclic nucleotide-gated channels are concentrated in cortical and hippocampal pyramidal cell dendrites, where they play an important role in determining synaptic integration and plasticity phenomena. These channels have been suggested to be involved in physiological processes such as cognition as well as pathophysiological states such as epilepsy, pain, Parkinson's disease (PD) and Alzheimer's disease (AD). Recent evidences from our own researches have suggested that the learning and memory impairments caused by chronic cerebral hypoperfusion (CCH) are associated with a change of HCN1/HCN2 expression; therefore these channels may also be therapeutic targets for treatment of vascular dementia. Keywords: Vascular dementia; HCN channels; Chronic cerebral hypoperfusion ReviewVascular dementia (VaD) is the second leading form of dementia after Alzheimer's disease (AD) among western countries [1]. It is a progressive disease caused by cerebrovascular diseases with the pathologic features of reduced blood flow in the brain that affects cognitive abilities [2][3][4]. Accordingly, the cognitive impairment associated with vessel disorders is an increasingly important and recognised area of the medicine of VaD patients. CCH is a common consequence of various cerebral vascular disorders and hemodynamic changes that contributes to the risk of VaD. In rodents, the bilateral common carotid artery occlusion (2VO) model is so far the most effective and frequently-used experimental model to evaluate the relation between chronic cerebral hypoperfusion and vascular diseaserelated dementia [2,[5][6][7]. However, the progress on understanding the basis of the disease and developing treatments is not encouraging. There are no drugs licensed for the treatment of VaD. In this context, we reviewed the discoveries from our own research based on 2VO model that the role of HCN channels in CCH-induced cognitive impairments and hypothesise a new therapeutic target toward developing novel treatments for dementia of vascular origin.HCN channels are cation channels that open at membrane voltages close to resting membrane potentials and are directly regulated by the binding of cAMP. It was identified in the late 1970s in sinoatrial node cells and neurons [8][9][10][11]. The HCN channel family is comprised of four subtypes (HCN1-4). The predominant forms in the hippocampus and cortex are HCN1 and HCN2 [12,13]. In pyramidal and neocortical neurons, they show a large gradient of expression that can be 60-fold increase from somatic to distal apical dendritic membranes [14]. The channels are formed by heteromeric or homomeric complexes and carry the hyperpolarization-activated current, Ih. In neuronal dendrites, Ih is proposed to be responsible for several important cellular functions and plays a fundamental role in controlling cellular excitability, rhythmic activity, dendritic integration, synaptic transmission, and plasticity phenomena [15][16][17] that participates in the pathogenic mechanism of certain neurolog...

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ESC‐sEVs Rejuvenate Senescent Hippocampal NSCs by Activating Lysosomes to Improve Cognitive Dysfunction in Vascular Dementia

Xia

Zhang

et al. 2020

Advanced Science

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Vascular dementia (VD) is one of the most common types of dementia, however, the intrinsic mechanism is unclear and there is still lack of effective medications. In this study, the VD rats exhibit a progressive cognitive impairment, as well as a time‐related increasing in hippocampal neural stem cells (H‐NSCs) senescence, lost and neurogenesis decline. Then, embryonic stem cell‐derived small extracellular vesicles (ESC‐sEVs) are intravenously injected into VD rats. ESC‐sEVs treatment significantly alleviates H‐NSCs senescence, recovers compromised proliferation and neuron differentiation capacity, and reverses cognitive impairment. By microarray analysis and RT‐qPCR it is identified that several miRNAs including miR‐17‐5p, miR‐18a‐5p, miR‐21‐5p, miR‐29a‐3p, and let‐7a‐5p, that can inhibit mTORC1 activation, exist in ESC‐sEVs. ESC‐sEVs rejuvenate H‐NSCs senescence partly by transferring these miRNAs to inhibit mTORC1 activation, promote transcription factor EB (TFEB) nuclear translocation and lysosome resumption. Taken together, these data indicate that H‐NSCs senescence cause cell depletion, neurogenesis reduction, and cognitive impairment in VD. ESC‐sEVs treatment ameliorates H‐NSCs senescence by inhibiting mTORC1 activation, and promoting TFEB nuclear translocation and lysosome resumption, thereby reversing senescence‐related neurogenesis dysfunction and cognitive impairment in VD. The application of ESC‐sEVs may be a novel cell‐free therapeutic tool for patients with VD, as well as other aging‐related diseases.

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Models and mechanisms of vascular dementia

Cited by 267 publications

References 164 publications

Vaskularni kognitivni upad in vaskularna demenca

Vaskularni kognitivni upad in vaskularna demenca

HCN Channels: From the Role in Chronic Cerebral Hypoperfusion-Induced Cognitive Impairments to a New Therapeutic Target for Vascular Dementia

ESC‐sEVs Rejuvenate Senescent Hippocampal NSCs by Activating Lysosomes to Improve Cognitive Dysfunction in Vascular Dementia

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