Experimental Rodent Models of Vascular Dementia: A Systematic Review

2021 ◽  
Vol 19 ◽  
Author(s):  
Nidhi Tiwari ◽  
Jyoti Upadhyay ◽  
Mohd Nazam Ansari ◽  
Syed Shadab Raza ◽  
Wasim Ahmad ◽  
...  
Keyword(s):  
Vascular Dementia ◽  
Small Vessel Disease ◽  
Current Knowledge ◽  
Vascular Cognitive Impairment ◽  
Experimental Models ◽  
New Drugs ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
The Brain ◽  
Large Vessel Disease

: Vascular dementia (VaD) occurs due to cerebrovascular insufficiency, which leads to decreased blood circulation to the brain, thereby resulting in mental disabilities. The main causes of vascular cognitive impairment (VCI) are severe hypoperfusion, stroke, hypertension, large vessel disease (cortical), small vessel disease (subcortical VaD), strategic infarct, hemorrhage (microbleed), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and cerebral amyloid angiopathy (CAA),which leads to decreased cerebrovascular perfusion. Many metabolic disorders such as diabetes mellitus (DM), dyslipidemia, and hyperhomocysteinemia are also related to VaD. The rodent experimental models provide a better prospective for the investigation of the molecular mechanism of new drugs. A plethora of experimental models are available that mimic the pathological conditions and lead to VaD. This review article updates the current knowledge on the basis of VaD, risk factors, pathophysiology, mechanism, advantages, limitations, and the modification of various available rodent experimental models.

Epidemiology and aetiopathogenesis

2020 ◽  
pp. 9-24
Author(s):  
Timothy J. England
Keyword(s):  
Small Vessel Disease ◽  
The Elderly ◽  
Developed Countries ◽  
Amyloid Angiopathy ◽  
Ageing Population ◽  
Vessel Disease ◽  
The Brain ◽  
Spontaneous Intracerebral Haemorrhage ◽  
Pathological Subtypes ◽  
Large Vessel Disease

Stroke is a common disabling condition associated with a high mortality, especially in the elderly. Subsequent social and monetary costs are high and despite a decreasing incidence of stroke in developed countries in recent years, prevalence has not declined due to an ageing population. Chapter 2 deals with ‘Epidemiology and aetiopathogenesis’ and examines the definitions of stroke and its pathological subtypes; epidemiology on a worldwide basis; age-specific data; mortality rates; cerebral blood flow and its relationship with ischaemic thresholds; and macroscopic and microscopic changes in the brain with increasing age and their relationship with ischaemic and haemorrhagic strokes. Changes related to large vessel disease, cardioembolism, small vessel disease, inflammatory arteriopathies, spontaneous intracerebral haemorrhage and cerebral amyloid angiopathy, are also described.

Small vessel disease

2020 ◽  
pp. 203-212
Author(s):  
Fergus N Doubal ◽  
Anna Poggesi ◽  
Leonardo Pantoni ◽  
Joanna M Wardlaw
Keyword(s):  
Small Vessel Disease ◽  
Current Knowledge ◽  
Intrinsic Disorder ◽  
Small Vessel ◽  
Imaging Features ◽  
World Region ◽  
Vessel Disease ◽  
Cerebral Arterioles ◽  
The Brain ◽  
Review Current

‘Small vessel disease’ describes a combination of neuroradiological and clinical features that are due to an intrinsic disorder of the small cerebral arterioles, capillaries, and venules in varying proportions. It is very common, usually sporadic, although rare monogenic forms are well described. The commonest presentations are with stroke or cognitive impairment. The cause of the small vessel abnormalities in the sporadic form is not well understood and the brain damage is generally attributed to ischaemia secondary to the vessel abnormality. However, evidence for altered microvessel function and blood brain barrier failure is accumulating. The commonest risk factors are increasing age, hypertension, smoking, and diabetes, but environmental and lifestyle factors are also important although poorly understood. Whether the imaging features or incidence of small vessel-related stroke or dementia vary by world region is unknown. We review current knowledge on presentation, aetiology, incidence, and prevalence of sporadic small vessel disease.

scholarly journals High On-Treatment Platelet Reactivity Affects the Extent of Ischemic Lesions in Stroke Patients Due to Large-Vessel Disease

2020 ◽  
Vol 9 (1) ◽  
pp. 251 ◽  
Author(s):  
Adam Wiśniewski ◽  
Joanna Sikora ◽  
Agata Sławińska ◽  
Karolina Filipska ◽  
Aleksandra Karczmarska-Wódzka ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Small Vessel Disease ◽  
Platelet Reactivity ◽  
Volume Measurement ◽  
Large Vessel ◽  
Vessel Disease ◽  
Fluid Attenuated Inversion Recovery ◽  
The Brain ◽  
Large Vessel Disease

Background: Excessive platelet activation and aggregation plays an important role in the pathogenesis of ischemic stroke. Correlation between platelet reactivity and ischemic lesions in the brain shows contradictory results and there are not enough data about the potential role of stroke etiology and its relationships with chronic lesions. The aim of this study is to assess the relationship between platelet reactivity and the extent of ischemic lesions with the particular role of etiopathogenesis. Methods: The study involved 69 patients with ischemic stroke, including 20 patients with large-vessel disease and 49 patients with small-vessel disease. Evaluation of platelet reactivity was performed within 24 h after the onset of stroke using two aggregometric methods (impedance and optical), while ischemic volume measurement in the brain was performed using magnetic resonance imaging (in diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences) at day 2–5 after the onset of stroke. Results: In the large-vessel disease subgroup, a correlation was found between platelet reactivity and acute ischemic focus volume (correlation coefficient (R) = 0.6858 and p = 0.0068 for DWI; R = 0.6064 and p = 0.0215 for FLAIR). Aspirin-resistant subjects were significantly more likely to have a large ischemic focus (Odds Ratio (OR) = 45.00, 95% Confidence Interval (CI) = 1.49–135.36, p = 0.0285 for DWI; OR = 28.00, 95% CI = 1.35–58.59, p = 0.0312 for FLAIR) than aspirin-sensitive subjects with large-vessel disease. Conclusion: In patients with ischemic stroke due to large-vessel disease, high on-treatment platelet reactivity affects the extent of acute and chronic ischemic lesions.

Vascular cognitive impairment and vascular dementia

2018 ◽  
Vol 11 (5) ◽  
pp. 249-255
Author(s):  
Anne M. Bonnici-Mallia ◽  
Christopher Barbara ◽  
Rahul Rao
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Cardiovascular Risk ◽  
Vascular Dementia ◽  
Small Vessel Disease ◽  
Vascular Cognitive Impairment ◽  
Common Type ◽  
Social Unit ◽  
Vessel Disease ◽  
Diagnosis Of Dementia

Vascular dementia is the second-most-common type of dementia. Vascular cognitive impairment is a term encompassing vascular dementia as well as milder forms of pre-dementia cognitive impairment related to vascular damage that do not meet the criteria for a diagnosis of dementia. Early diagnosis of cerebrovascular disease, including silent infarcts and small vessel disease is difficult, but important, as modification of cardiovascular risk factors is the mainstay of management to decrease further insults and deterioration, and maintain the patient’s independence within their family and social unit.

Subcortical Ischemic Vascular Disease and Dementia

2003 ◽  
Vol 15 (S1) ◽  
pp. 23-26 ◽  
Author(s):  
Timo Erkinjuntti
Keyword(s):  
White Matter ◽  
Vascular Disease ◽  
Small Vessel Disease ◽  
White Matter Lesions ◽  
Vascular Cognitive Impairment ◽  
Vessel Disease ◽  
Primary Location ◽  
Primary Type ◽  
Research Criteria ◽  
The Brain

Subcortical ischemic vascular disease and dementia (SIVD) incorporate small vessel disease as the chief vascular etiology, lacunar infarct and ischemic white-matter lesions (WMLs) as primary type of brain lesions, subcortical location as the primary location of lesions, and subcortical syndrome as the primary clinical manifestation. It incorporates two clinical entities: Binswanger's syndrome and the lacunar state. Patients with SIVD present with extensive white-matter lesions and multiple lacunae on neuroimaging. SIVD is expected to be a more homogenous subtype of vascular cognitive impairment and dementia. Recently modified NINDS-AIREN research criteria for SIVD have been proposed. Further empirical research is needed to refine the syndrome and stages and validate the brain imaging criteria, as well as to detail the natural history and outcomes of SIVD.

scholarly journals Cerebral Small Vessel Disease and Cerebral Amyloid Angiopathy

2019 ◽  
Author(s):  
Raffaella Valenti
Keyword(s):  
Cognitive Rehabilitation ◽  
Small Vessel Disease ◽  
Prognostic Significance ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Elderly Subjects ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
Cerebral Amyloid ◽  
The Brain

Sporadic cerebral small vessel disease (SVD) is considered to be among the most commonly known neuropathological processes in the brain, hosting a crucial role in stroke, cognitive impairment, and functional loss in elderly subjects. We investigated clinical (neuroimaging and cognitive) biomarkers in the SVD, through a series of analyses from our five studies. Sporadic cerebral SVD is a complex ‘micro-world’ to be globally considered. All the relevant lesion types and SVD neuroimaging burden should be taken into account. The cumulative effects of microangiopathy burden in the brain of patients affected by SVD are crucial. Cognitive rehabilitation could represent a promising approach to prevent vascular dementia or to improve cognitive performances in patients with cerebral SVD. Longitudinal studies may provide more robust information about the progression and prognostic significance of our findings.

scholarly journals Perturbations of the cerebrovascular matrisome: A convergent mechanism in small vessel disease of the brain?

2015 ◽  
Vol 36 (1) ◽  
pp. 143-157 ◽  
Author(s):  
Anne Joutel ◽  
Iman Haddad ◽  
Julien Ratelade ◽  
Mark T Nelson
Keyword(s):  
Small Vessel Disease ◽  
Current Knowledge ◽  
Experimental Models ◽  
Small Vessel ◽  
Brain Vessels ◽  
Cellular Processes ◽  
Vessel Disease ◽  
Specialized Form ◽  
Unique Composition ◽  
Communication Pathway

The term matrisome refers to the ensemble of proteins constituting the extracellular matrix (ECM) (core matrisome) as well as the proteins associated with the ECM. Every organ has an ECM with a unique composition that not only provides the support and anchorage for cells, but also controls fundamental cellular processes as diverse as differentiation, survival, proliferation, and polarity. The current knowledge of the matrisome of small brain vessels is reviewed with a focus on the basement membrane (BM), a specialized form of ECM located at the interface between endothelial cells, contractile cells (smooth muscle cells and pericytes), and astrocyte endfeet—a very strategic location in the communication pathway between the cerebral microcirculation and astrocytes. We discuss some of the most recent genetic data and relevant findings from experimental models of nonamyloid cerebral small vessel disease (SVD). We propose the concept that perturbations of the cerebrovascular matrisome is a convergent pathologic pathway in monogenic forms of SVD, and is likely relevant to the sporadic disease.

Neuropathology of Vascular Cognitive Impairment and Vascular Dementia

2003 ◽  
Vol 15 (S1) ◽  
pp. 71-75 ◽  
Author(s):  
Paul G. Ince ◽  
Malee S. Fernando
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Vascular Dementia ◽  
Small Vessel Disease ◽  
The Elderly ◽  
Vascular Cognitive Impairment ◽  
Vessel Disease ◽  
Clinicopathological Correlations ◽  
The Impact ◽  
Major Emphasis

Understanding of vascular substrates of cognitive decline in the elderly is evoloving to include a major emphasis on the impact of small vessel disease (SVD). While existing concepts of multi-infarct dementia and strategic infarct dementia remain valid, they present difficulty in generalizing clinicopathological correlations from patient to patient. The range and significance of lesions that should be included as manifestations of SVD are unresolved, as is their impact on, and association with, neurodegenerative changes. This mini-review summarizes the authors' views on SVD substrates leading to cognitive decline and proposes priorities for pathological investigations of human cerebrovascular mechanisms leading to cognitive decline.

scholarly journals Significance of Cortical Micro-Infarcts in the Human Brain

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Jacques L De Reuck
Keyword(s):  
Vascular Dementia ◽  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
White Matter Changes ◽  
Vessel Disease ◽  
Neurodegenerative Dementia ◽  
Cerebral Amyloid

Cortical micro-infarcts are due to cerebral small vessel disease. In contrast to the arteriosclerotic type of cerebral small vessel disease, cortical micro-infarcts are mainly related and due to cerebral amyloid angiopathy. Alzheimer’s disease is the most frequent neurodegenerative dementia disease associated to cerebral amyloid angiopathy and cortical micro-infarcts. Vascular dementia cannot only be due to lacunar infarcts and ischemic white matter changes, but can also be caused by cortical micro-infarcts. The latter are a frequent cause of vascular dementia and decrease globally the cerebral blood flow.

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