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MYPT1SMKO Mice Function as a Novel Spontaneous Age- and Hypertension-Dependent Animal Model of CSVD
AbstractCerebral small vessel disease (CSVD) is the most common progressive vascular disease that causes vascular dementia. Aging and hypertension are major contributors to CSVD, but the pathophysiological mechanism remains unclear, mainly due to the lack of an ideal animal model. Our previous study revealed that vascular smooth muscle cell (VSMC)-specific myosin phosphatase target subunit 1 (MYPT1) knockout (MYPT1SMKO) leads to constant hypertension, prompting us to explore whether hypertensive MYPT1SMKO mice can be considered a novel CSVD animal model. Here, we found that MYPT1SMKO mice displayed age-dependent CSVD-like ...
Source: Translational Stroke Research - February 27, 2023 Category: Neurology Source Type: research

Exercise Improves Cerebral Blood Flow and Functional Outcomes in an Experimental Mouse Model of Vascular Cognitive Impairment and Dementia (VCID)
AbstractVascular cognitive impairment and dementia (VCID) are a growing threat to public health without any known treatment. The bilateral common carotid artery stenosis (BCAS) mouse model is valid for VCID. Previously, we have reported that remote ischemic postconditioning (RIPostC) during chronic cerebral hypoperfusion (CCH) induced by BCAS increases cerebral blood flow (CBF), improves cognitive function, and reduces white matter damage. We hypothesized that physical exercise (EXR) would augment CBF during CCH and prevent cognitive impairment in the BCAS model. BCAS was performed in C57/B6 mice of both sexes to establish...
Source: Translational Stroke Research - January 23, 2023 Category: Neurology Source Type: research

Recurrent Transient Ischemic Attack Induces Neural Cytoskeleton Modification and Gliosis in an Experimental Model
AbstractTransient ischemic attack (TIA) presents a high risk for subsequent stroke, Alzheimer ’s disease (AD), and related dementia (ADRD). However, the neuropathophysiology of TIA has been rarely studied. By evaluating recurrent TIA-induced neuropathological changes, our study aimed to explore the potential mechanisms underlying the contribution of TIA to ADRD. In the current study, we es tablished a recurrent TIA model by three times 10-min middle cerebral artery occlusion within a week in rat. Neither permanent neurological deficit nor apoptosis was observed following recurrent TIA. No increase of AD-related biomarker...
Source: Translational Stroke Research - July 22, 2022 Category: Neurology Source Type: research

Transcriptomic Profiling Reveals Discrete Poststroke Dementia Neuronal and Gliovascular Signatures
AbstractPoststroke dementia (PSD) is associated with pathology in frontal brain regions, in particular dorsolateral prefrontal cortex (DLPFC) neurons and white matter, remote from the infarct. We hypothesised that PSD results from progressive DLPFC neuronal damage, associated with frontal white matter gliovascular unit (GVU) alterations. We investigated the transcriptomic profile of the neurons and white matter GVU cells previously implicated in pathology. Laser-capture microdissected neurons, astrocytes and endothelial cells were obtained from the Cognitive Function After Stroke cohort of control, PSD and poststroke non-d...
Source: Translational Stroke Research - May 31, 2022 Category: Neurology Source Type: research

Complement C3a Receptor (C3aR) Mediates Vascular Dysfunction, Hippocampal Pathology, and Cognitive Impairment in a Mouse Model of VCID
AbstractVascular contributions to cognitive impairment and dementia (VCID) secondary to chronic mild-moderate cerebral ischemia underlie a significant percentage of cases of dementia. We previously reported that either genetic deficiency of the complement C3a receptor (C3aR) or its pharmacological inhibition protects against cerebral ischemia in rodents, while others have implicated C3aR in the pathogenesis seen in rodent transgenic models of Alzheimer ’s disease. In the present study, we evaluated the role of complement C3a-C3aR signaling in the onset and progression of VCID. We utilized the bilateral common carotid art...
Source: Translational Stroke Research - March 8, 2022 Category: Neurology Source Type: research

A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy
We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6  years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical...
Source: Translational Stroke Research - August 20, 2021 Category: Neurology Source Type: research

Electrophilic and Drug-Induced Stimulation of NOTCH3 N-terminal Fragment Oligomerization in Cerebrovascular Pathology
AbstractSmall vessel disease is a prevalent age-related condition linked to increased risk of dementia and stroke. We investigate the most commonly inherited form, CADASIL, caused by cysteine-involving mutations inNOTCH3. Recent studies highlight accumulation of NOTCH3 N-terminal fragmentation product (NTF) in disease. In vitro, NTF is capable of both spontaneous and catecholamine-enhanced cysteine-mediated oligomerization. Despite well-characterized genetic influence on CADASIL, environmental effects, including medication usage, on disease remain unclear. We studied effects of assorted electrophilic compounds and drugs on...
Source: Translational Stroke Research - May 3, 2021 Category: Neurology Source Type: research

Calcium/Calmodulin –Dependent Protein Kinase II in Cerebrovascular Diseases
AbstractCerebrovascular disease is the most common life-threatening and debilitating condition that often leads to stroke. The multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII) is a key Ca2+ sensor and an important signaling protein in a variety of biological systems within the brain, heart, and vasculature. In the brain, past stroke-related studies have been mainly focused on the role of CaMKII in ischemic stroke in neurons and established CaMKII as a major mediator of neuronal cell death induced by glutamate excitotoxicity and oxidative stress following ischemic stroke. However, with growing underst...
Source: Translational Stroke Research - March 13, 2021 Category: Neurology Source Type: research

Modeling Mixed Vascular and Alzheimer ’s Dementia Using Focal Subcortical Ischemic Stroke in Human ApoE4-TR:5XFAD Transgenic Mice
AbstractSubcortical white matter ischemic lesions are increasingly recognized to have pathologic overlap in individuals with Alzheimer ’s disease (AD). The interaction of white matter ischemic lesions with amyloid pathology seen in AD is poorly characterized. We designed a novel mouse model of subcortical white matter ischemic stroke and AD that can inform our understanding of the cellular and molecular mechanisms of mixed vascul ar and AD dementia. Subcortical white matter ischemic stroke underlying forelimb motor cortex was induced by local stereotactic injection of an irreversible eNOS inhibitor. Subcortical white mat...
Source: Translational Stroke Research - February 20, 2020 Category: Neurology Source Type: research

From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid- β Formation
AbstractStroke and Alzheimer ’s disease (AD) are cerebral pathologies with high socioeconomic impact that can occur together and mutually interact. Vascular factors predisposing to cerebrovascular disease have also been specifically associated with development of AD, and acute stroke is known to increase the risk to develop d ementia.Despite the apparent association, it remains unknown how acute cerebrovascular disease and development of AD are precisely linked and act on each other. It has been suggested that this interaction is strongly related to vascular deposition of amyloid- β (Aβ), i.e., cerebral amyloid angiopa...
Source: Translational Stroke Research - November 27, 2019 Category: Neurology Source Type: research

Texture Features of Magnetic Resonance Images: an Early Marker of Post-stroke Cognitive Impairment
AbstractStroke is frequently associated with delayed, long-term cognitive impairment (CI) and dementia. Recent research has focused on identifying early predictive markers of CI occurrence. We carried out a texture analysis of magnetic resonance (MR) images to identify predictive markers of CI occurrence based on a combination of preclinical and clinical data. Seventy-two-hour post-stroke T1W MR images of 160 consecutive patients were examined, including 75 patients with confirmed CI at the 6-month post-stroke neuropsychological examination. Texture features were measured in the hippocampus and entorhinal cortex and compar...
Source: Translational Stroke Research - October 31, 2019 Category: Neurology Source Type: research

Treadmill Exercise Suppresses Cognitive Decline and Increases White Matter Oligodendrocyte Precursor Cells in a Mouse Model of Prolonged Cerebral Hypoperfusion
AbstractClinical evidence suggests that patients with subcortical ischemic vascular dementia (SIVD) perform better at cognitive tests after exercise. However, the underlying mechanism for this effect is largely unknown. Here, we examined how treadmill exercise changes the cognitive function and white matter cellular pathology in a mouse model of SIVD. Prolonged cerebral hypoperfusion was induced in 2-month-old male C57BL/6J mice by bilateral common carotid artery stenosis. A week later, the mice were randomly divided into a group that received 6-week treadmill exercise and a sedentary group for observation. In multiple beh...
Source: Translational Stroke Research - October 11, 2019 Category: Neurology Source Type: research

Management of Cerebral Microbleeds in Clinical Practice
AbstractCerebral microbleeds (CMBs) are very frequent diagnoses with MRI imaging in the elderly or in patients with cerebral infarction, intracranial hemorrhage (ICH), and dementia. The mechanisms for CMBs are not fully understood but may be secondary to injury to the vascular wall from long-standing hypertension or amyloid deposition in the tissue. The presence of CMB increases the risk for stroke, dementia, and death. The increasing number of CMBs is also associated with a higher risk of hemorrhagic complications with the long-term use of anticoagulants in atrial fibrillation and in patients requiring thrombolysis for ac...
Source: Translational Stroke Research - December 15, 2018 Category: Neurology Source Type: research

Redistribution of Mature Smooth Muscle Markers in Brain Arteries in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy
AbstractVascular smooth muscle cells (SMCs) undergo a series of dramatic changes in CADASIL, the most common inherited cause of vascular dementia and stroke. NOTCH3 protein accumulates and aggregates early in CADASIL, followed by loss of mature SMCs from the media of brain arteries and marked intimal proliferation. Similar intimal thickening is seen in peripheral arterial disease, which features pathological intimal cells including proliferative, dedifferentiated, smooth muscle-like cells deficient in SMC markers. Limited studies have been performed to investigate the differentiation state and location of SMCs in brain vas...
Source: Translational Stroke Research - June 22, 2018 Category: Neurology Source Type: research

Hippocampal Deformations and Entorhinal Cortex Atrophy as an Anatomical Signature of Long-Term Cognitive Impairment: from the MCAO Rat Model to the Stroke Patient
AbstractStroke patients have an elevated risk of developing long-term cognitive disorders or dementia. The latter is often associated with atrophy of the medial temporal lobe. However, it is not clear whether hippocampal and entorhinal cortex atrophy is the sole predictor of long-term post-stroke dementia. We hypothesized that hippocampal deformation (rather than atrophy) is a predictive marker of long-term post-stroke dementia on a rat model and tested this hypothesis in a prospective cohort of stroke patients.Male Wistar rats were subjected to transient middle cerebral artery occlusion and assessed 6  months later. Nine...
Source: Translational Stroke Research - October 16, 2017 Category: Neurology Source Type: research

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